for management of
thyroid cancer
British Thyroid Association
Royal College of Physicians

Acknowledgements Grateful thanks a re expressed to the many reviewers of the guidelines; these included leading international experts in thyroid cancer, hospital specialists, primary care physicians and patients. They devoted much time and care to considering the document and their recommendations and suggestions for improvements were most valuable. Contents
Thyroid cancer guidelines update group
Original (2002) thyroid cancer guidelines development group Notes on the development and use of the guidelines Types of evidence and the grading of recommendations Abbreviations
KEY RECOMMENDATIONS AND OVERVIEW OF MANAGEMENT OF THYROID CANCER (DIFFERENTIATED AND MEDULLARY) 1. Access to a multidisciplinary thyroid cancer team 2. Patient focus 5 Radioiodine (131I) ablation / therapy and external beam radiotherapy 6 Aims of treatment 7. Summary of management of differentiated thyroid cancer 8. Follow-up of differentiated thyroid cancer 9. Medullary thyroid cancer 1. INTRODUCTION 1.1 The need for guidelines 1.2 Aim of the guidelines 1.4 Prognostic factors 1.5 Public health and prevention PRESENTATION, DIAGNOSIS AND REFERRAL 2.1 Symptoms or signs that warrant investigation 2.2 Physical examination 2.3 Appropriate investigations pending hospital appointment 2.4 Who to refer to? 2.5 The role of the multidisciplinary teams 2.6 Hospital investigations 2.7 Communicating the diagnosis FINE NEEDLE ASPIRATION CYTOLOGY 3.1 Aspiration cytology of thyroid 3.2 Diagnostic categories 4 PRIMARY TREATMENT OF DIFFERENTIATED THYROID CANCER 4.1 Timescale 4.2 Staging and risk assignment SURGERY FOR DIFFERNETIATED THYROID CANCER 5.1 Preparation for surgery 5.2 Elective surgical treatment for thyroid cancer 5.3 Emergency surgery 5.4 Surgery for locally advanced disease 5.5 Early post-surgical management of differentiated thyroid cancer 5.6 Medullary thyroid cancer 5.7 Surgical management of other rare malignancies of thyroid 6. RADIOIODINE ABLATION AND THERAPY FOR DIFFERENTIATED THYROID CANCER 6.1 Preparation for 131I ablation or therapy 6.3 Diagnostic scan (131I 74 to 150 MBq) 6.4 Short term and long term side effects of 131I ablation and therapy 7.1 Adjuvant external beam radiotherapy 7.2 High dose external beam radiotherapy as part of primary treatment 8. POST-TREATMENT 8.1 Voice dysfunction 8.2 Management of hypocalcaemia 8.3 Long-term suppression of serum thyrotrophin (TSH) 8.4 Role of measurement of serum thyroglobulin (Tg) in long-term follow-up 8.5 Role of imaging by ultrasonography and whole body 131I scanning in routine follow-up RECURRENT / PERSISTENT DIFFERENTIATED THYROID CANCER 9.1 Recurrence in the thyroid bed or cervical lymph nodes 9.2 Metastatic disease involving lung and other soft tissue areas 9.3 Bone metastases 9.4 Cerebral metastases 9.5 Other Metastatic sites 9.6 Unknown Metastatic sites 9.7 Palliative care LONG-TERM FOLLOW-UP OF DIFFERENTIATED THYROID CANCER PREGNANCY AND THYROID CANCER 11.1 Diagnosis of thyroid cancer in pregnancy 11.2 Pregnancy in the treated patient 12. THYROID CANCER IN CHILDHOOD 13. PATHOLOGICAL REPORTING, GRADING AND STAGING OF THYROID CANCERS 13.1 General principles 13.2 Gross description 13.3 Microscopic report 13.4 Pathological staging 13.5 Staging protocol 13.6 Grading of tumours MANAGEMENT OF MEDULLARY THYROID CANCER (MTC) 14.2 Hospital investigation 14.6 Molecular genetics 14.7 MEN-2B 15. REGISTRATION, CORE DATASET AND AUDIT 16. THYROID CANCER : A GUIDE FOR PRIMARY CARE PHYSICIANS 16.1 Raising awareness 16.4 Diagnosis and referral 16.5 Algorithm for diagnosis & management of a thyroid nodule or suspected thyroid cancer in general practice 16.6 Follow up APPENDIX 1. ASSAY METHODOLOGY APPENDIX 2. RECOGNITION OF MEN-2B APPENDIX 3. SEARCH METHODOLOGY APPENDIX 4. REFERENCES APPENDIX 5. PATIENT INFORMATION LEAFLETS Thyroid cancer guidelines update group
Susan EM Clarke MSc, FRCP, FRCR, Consultant Physician/ Senior Lecturer, Guys and St Thomas' Hospital,
Jayne Franklyn MD, PhD, FRCP, FMedSci, Professor of Medicine, Birmingham
Georgina Gerrard BSc, MB, BChir, MRCP, FRCR, Consultant in Clinical Oncology, Leeds
Barney Harrison MS, FRCS(Eng), FRCS(Ed), Consultant Endocrine Surgeon, Sheffield
Janis Hickey, Patients' representative and President, British Thyroid Foundation, Harrogate
Pat Kendall-Taylor MD, DCH, FRCP, Emeritus Professor of Endocrinology, Newcastle-upon-Tyne
Anne Marie McNicol BSc, MD, MRCP(UK), FRCPGlas, FRCPath, Reader in Pathology, University of Glasgow,
Consultant Pathologist, Glasgow
Ujjal K. Mallick MB, BS MS, FRCR, Consultant Clinical Oncologist, Newcastle-upon-Tyne
Petros Perros (Chairman) MD, FRCP, Consultant Endocrinologist, Newcastle-upon-Tyne
Malcolm Prentice BSc, FRCP, Consultant Physician and Endocrinologist, Mayday University Hospital, Croydon
Rajesh V Thakker MD, FRCP, FRCPath, FMedSci, May Professor of Medicine, Oxford
John Watkinson MSC, MS, FRCS (Ed,Glas,London), DLO Consultant Otolaryngologist/Head & Neck
Surgeon, Birmingham
Anthony P Weetman MD, DSc, FRCP, FMedSci, Professor of Medicine and Dean of Medicine, Sheffield

Original (2002) thyroid cancer guidelines development group
Geoffrey J Beckett BSc, PhD, FRCPath, Reader in Clinical Biochemistry, Edinburgh
Penny M Clark PhD, FRCPath, Consultant Clinical Scientist, Birmingham
Susan EM Clarke MSc, FRCP, Consultant Physician/ Senior Lecturer, Guys and St Thomas' Hospital, London
Richard Collins FRCS(Eng), FRCS(Ed), Consultant Surgeon, Canterbury
Sharon Dobbins Chief Librarian, Sunderland Royal Hospital Trust
John Farndon, BSc, MD, FRCS, Professor of Surgery, University of Bristol
Jayne Franklyn MD, PhD, FRCP, FMedSci, Professor of Medicine, Birmingham
Caroline Owen Hafiz MSc, RGN, Head and Neck Support Counsellor/Nurse
Queen Elizabeth Hospital, Birmingham
Clive Harmer FRCP, FRCR, Head of Thyroid Unit, Royal Marsden NHS Trust, London
GAW Hornett MA, FRCGP, General Practitioner, Wonersh, Guildford
Julian Kabala FRCR, Consultant Radiologist, Bristol
Pat Kendall-Taylor (Chairman) MD, DCH, FRCP, Professor of Endocrinology, Newcastle-upon-Tyne
Julia Lawrence, Patient, Chipping Sodbury
Anne Marie McNicol BSc, MD, MRCP(UK), FRCPGlas, FRCPath, Reader in Pathology, University of Glasgow,
Consultant Pathologist, Glasgow
Ujjal K. Mallick , MB.BS, MS, FRCR, Consultant Clinical Oncologist, Newcastle-upon-Tyne
Petros Perros MD, FRCP, Consultant Physician and Endocrinologist, Newcastle-upon-Tyne
Malcolm Prentice BSc, FRCP, Consultant Physician and Endocrinologist, Mayday University Hospital, Croydon,
George Proud MD, FRCS, Consultant Endocrine Surgeon, Newcastle-upon-Tyne
Catharine Sturgeon BSc, PhD, Principal Clinical Scientist, Edinburgh
John Watkinson FRCS, Consultant Otolaryngologist/Head & Neck Surgeon, Birmingham
AP Weetman MD, DSc, FRCP, Professor of Medicine and Dean of Medicine, Sheffield
Jackie Williams, Patient, Ascot, Berkshire
Louiza Vini, Observer, Clinical Oncologist, Royal Marsden Hospital, London
Professional bodies represented
British Association of Endocrine and Thyroid Surgeons
British Association of Head and Neck Oncologists of Great Britain
British Association of Otolaryngologists/Head & Neck Surgeons (BAOL- HNS),
British Association of Surgical Oncologists (BASO)
British Nuclear Medicine Society
British Thyroid Association
British Thyroid Foundation
Royal College of Pathologists
Royal College of Physicians (Nuclear Medicine Committee)
Royal College of Physicians (Diabetes and Endocrinology Committee)
Royal College of Radiologists, Faculty of Clinical Oncology
Royal College of Surgeons (Eng)
Society for Endocrinology
UK Endocrine Pathologist Society
Invited Specialist Reviewers from whom comments were received on updated guidelines
Ms S Allen, Consultant Physicist, London (British Nuclear Medicine Society)
Professor N Bundred, Professor in Surgical Oncology, Manchester (British Association Of Surgical Oncology)
Professor JA Fagin, Chief, Endocrinology Service, Sloan-Kettering Cancer Center, New York, USA (British
Thyroid Association)
Mr A Gandhi Consultant Breast & Endocrine Surgeon, Manchester, (British Association of Thyroid and Endocrine
Dr TE Giles, Consultant Cytopathologist, Royal Liverpool University Hospital, (British Society of Clinical
Professor J Lazarus, Professor of Clinical Endocrinology, Cardiff (Royal College of Physicians, Endocrinology
and Diabetes representative)
Dr V Lewington, Consultant Nuclear Medicine Physician, London (Royal College of Physicians and British
Nuclear Medicine Society).
Dr N Reed, Consultant Clincal Oncologist, Glasgow (Faculty of Clinical Oncology, Royal College of Radiology)
Mr N Roland, Consultant ENT / Head and Neck Surgeon, Liverpool (British Association of Head and Neck
Dr S Vinjamuri, Consultant in Nuclear Medicine, Liverpool (British Nuclear Medicine Society)
Notes on the development and use of the guidelines

Development of the Guidelines
The Thyroid Cancer Guidelines were first published in 2002 after extensive review of the literature by
representatives of professional and patient-led organisations (Royal Colleges of Physicians, Radiologists,
Surgeons, Pathologists, General Practitioners, Nurses, the British Association of Endocrine Surgeons, the British
Association of Otolaryngologists and Head and Neck Surgeons (BAOL-HNS), the British Association of Head and
Neck Oncologists of Great Britain (BAHNO), the British Nuclear Medicine Society, the Society for
Endocrinology and the British Thyroid Foundation) and external refereeing.
The guidelines were updated in 2006 by a subgroup representing the majority of the same professional
organisations, in the light of recent advances in diagnosis and management of thyroid cancer. The updated
guidelines place emphasis on tailoring the aggressiveness of treatment and monitoring to the individual patient, and
the central role of the Multidisciplinary team meetings in making these decisions based on risk assessment. In
addition, the updated guidelines incorporate issues that have arisen as a result of the implementation of waiting
times of the Cancer Plan and the publication of "Improving Outcomes in Head and Neck cancer" by the National
Institute of Clinical Excellence in 2004.
The updated guidelines were reviewed by several members of the original guideline group and by other external
referees before publication.

The intention
is that the guidelines be adopted by the individual Regional Cancer Networks, after discussion by
local clinical and managerial staff, and with the addition of appropriate arrangements, for use in the specific
This document should be considered as a guideline only; it is not intended to serve as a standard of medical care. It
should not be construed as including all the acceptable methods of care. The management plan for an individual
patient must be made by the Multidisciplinary team in the light of the clinical data and the diagnostic and treatment
options available.
The focus of the document is the management of thyroid cancer, rather than investigation of thyroid nodules. The
guideline focuses mainly on thyroid cancer in adult patients although childhood thyroid cancer is included in the
section on medullary thyroid cancer. Guidelines on thyroid cancer in children can be found elsewhere.
It is hoped that the document will provide guidance for primary care physicians, general physicians,
endocrinologists, surgeons, oncologists, nuclear medicine physicians, radiologists, medical physicists, biochemists
and nurses, as well as those involved in managerial roles.
The guidelines are also intended to provide a basis for local and national audit and each section offers
recommendations that are suitable for the audit process.
Funding: The updated guidelines were generously supported by the British Thyroid Association.
Declaration of conflict of interests: Dr S Clarke, Dr G Gerrard, Dr Mallick and P Perros have received support
from Genzyme for attendance to educational meetings.
These guidelines may be photocopied or down-loaded from the BTA web site:

Types of evidence and the grading of recommendations

The definition of Types of Evidence and the Grading of Recommendations used in the guidelines follows that of
the Agency for Health Care Policy and Research (AHCPR), as set out below:

Type of evidence (based on AHCPR 1992

Type of evidence
Evidence obtained from meta-analysis of randomised controlled trials. Evidence obtained from at least one randomised controlled trial. Evidence obtained from at least one well-designed controlled study without randomisation. Evidence obtained from at least one other type of well-designed quasi-experimental study. Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case control studies. Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities.

Grading of recommendations (based on AHCPR 1994

Requires at least one randomised controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation.
Requires availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendation. Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly
Agency for Health Care Policy and Research (now Agency of Health Research and Quality) Administration of Radioactive Substances Advisory Committee (part of Health Protection British Association of Thyroid and Endocrine Surgeons BAOL- HNS: British Association of Otolaryngologists/Head & Neck Surgeons Differentiated Thyroid Cancer* Fluorescent Activated Cell Sorter 18 Fluoro-Deoxy-Glucose Familial Medullary Thyroid Cancer Fine Needle Aspiration Cytology Follicular Thyroid Cancer* Internal Jugular Vein Intensity Modulated Radiotherapy IRMA: Immunoradiometric Assay Metastases, Age at presentation, Completeness of surgical resection, Invasion (extrathyroidal), Size Mucosa Associated Lymphoid Tissue Minimum Level of Detection Multi Disciplinary Team Multiple Endocrine Neoplasia Modified Radical Neck Dissection Medullary Thyroid Carcinoma* Positron Emission Tomography Papillary Thyroid Cancer* pTNM: Pathologically staged according to Tumour size, Node metastases and distant Metastases rhTSH: Recombinant human TSH Radioimmunoassay Spinal Accessory Nerve Sternocleidomastoid muscle Triiodothyronine (liothyronine) Thyroxine (levothyroxine) TFT: Thyroid function tests Tg: Anti-thyroglobulin Antibodies Tumour Specific Group Thyroid Stimulating Hormone *Definitions of types of thyroid cancer used in the guidelines:
Thyroid Cancer:
Any primary thyroid malignancy (includes differentiated thyroid cancer, medullary thyroid cancer
anaplastic thyroid cancer, thyroid lymphoma and other very rare types).
Differentiated thyroid cancer: Papillary thyroid cancer and follicular thyroid cancer (includes Hürthle cell carcinoma)

Key recommendations and overview of management of
thyroid cancer (differentiated and medullary)

These guidelines refer to the investigation and management of differentiated (papillary and follicular) and
medullary thyroid cancer.

1 Access to a multidisciplinary thyroid cancer team

The management of differentiated thyroid cancer (a highly curable disease) and of medullary thyroid cancer should be the responsibility of a specialist multidisciplinary team (MDT), membership of which
will normally be appointed by the Regional Cancer Network (IV, C).
The timeframe for urgent referrals should comply with the Department of Health targets (section 2)
(IV, C).
The MDT will normally comprise surgeon, endocrinologist and oncologist (or nuclear medicine
physician) with support from pathologist, medical physicist, biochemist, radiologist, specialist nurse,
all with expertise and interest in the management of thyroid cancers (IV, C).
Patients will normally be seen by one or more members of the MDT; a combined clinic is
recommended. All members of the MDT should maintain continuing professional development (IV,

2 Patient focus

Patients should be offered full verbal and written information about their condition and their treatment
(Appendix 5) (IV, C).
Patients should have continuing access to a member of the MDT for guidance and support (IV, C).

3 Surgery (section 5)
The surgeon should have training and expertise in the management of thyroid cancer and be a member of
the MDT (IV, C).
4 Pathology (section 12)
Pathologists dealing with thyroid tumours should have expertise and interest in thyroid cytology and
histopathology (IV, C).
All patients should be staged by clinical and pathological TNM staging (III, B).
Patients should be assigned to the appropriate risk group (III, B). Low-risk patients are defined for the
purpose of these guidelines, as those in the TNM stage I, who have a probability of long-term survival
greater then 98%.

5 Radioiodine (131I) ablation / therapy and external beam radiotherapy
(section 6)
An oncologist (or nuclear medicine physician) with expertise and an interest in the management of
differentiated thyroid cancer should supervise this treatment and be a member of the MDT (IV, C).
Those administering therapeutic 131I must hold an appropriate ARSAC certificate or must administer 131I under the direction / supervision of an appropriate ARSAC certificate holder (IV, C).
131I ablation / therapy should only be carried out in centres with appropriate facilities (IV, C).
Aims of treatment
Removal of all tumour Elimination of clinical, radiological, or biochemical evidence of recurrence Minimisation of unwanted effects of treatment 7 Summary of management of differentiated thyroid cancer
All new patients should be seen by a member of the MDT, and the treatment plan should be discussed
and endorsed by the MDT (section 2.5) (IV, C).
Fine-needle aspiration cytology (FNAC ) should be used in the planning of surgery (section 3) (III, B).
Patients with papillary thyroid cancer (PTC) more than 1 cm in diameter or high risk follicular thyroid
cancer (FTC) should undergo near-total or total thyroidectomy. Patients with low risk (section 1.4)
FTC or PTC <1 cm may be treated with thyroid lobectomy alone (section 5.2) (III, B).
Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid
cancer, but not sooner than 6 weeks after surgery (section 8.4) (IV, C).
Patients will normally start on triiodothyronine 20 mcg tds (normal adult dosage) after the operation.
This should be stopped two weeks before 131I ablation or therapy (section 6.1) (IV, C).
The majority of patients with a tumour size of more than 1 cm in diameter, who have undergone a
near-total / total thyroidectomy, should have 131I ablation (section 5.2) (III, B).
Always exclude pregnancy and breast feeding before administering 131I (section 6.1) (IV, C).
Breast feeding should be stopped at least 4 weeks and preferably 8 weeks before 131I (section 6.1) and
should not resume breastfeeding (IV, C).
A post-ablation scan (3-10 days after 131I ablation) should be performed (section 6.2) (III, B).
Patients treated with 131I will require levothyroxine therapy in a dose sufficient to suppress the serum
TSH to < 0.1mIU/l (III, B). Levothyroxine can be commenced 3 days after 131I in a dose sufficient to
suppress TSH to <0.1mIU/L. In patients confirmed to be low-risk, a serum TSH <0.5mIU/L is
probably acceptable (section 8.3).
Reassessment with a whole body scan (WBS) after stopping levothyroxine for 4 weeks, and stimulated
serum Tg is indicated no earlier than 6 months after 131I ablation. If abnormal uptake of the tracer is
detectable, a 131I therapy dose should be given and a post-treatment scan (3-10 days after 131I therapy)
should be performed. Following this the patient should restart levothyroxine (section 8.4 & 8.5) (III,
In low risk (section 1.4) patients measurement of Tg after TSH stimulation alone (i.e. without a
diagnostic 131I whole body scan) may be adequate. In such cases ultrasonography of the neck 6-12
months after thyroidectomy is indicated (section 8.5) (III, B).
If there is suspicion of residual disease, further scans should be carried out, usually six months after 131I
therapy (IV, C).
External beam radiotherapy is only occasionally used, for patients with pT4 tumours (TNM staging) and presumed residual disease in the neck, which is not amenable to further surgery, particularly when the tumour does not take up 131I (section 7). External beam radiotherapy also has a role as a palliative measure in patients with advanced symptomatic local or distant disease (section 9). Follow-up of differentiated thyroid cancer

This should be life-long (IIb, B) because:
The disease has a long natural history Late recurrences are not rare, and can be treated successfully. Regular follow-up is necessary for monitoring of treatment (TSH suppression, the consequences of supraphysiological levothyroxine replacement, treatment of hypocalcaemia). Life-long suppression of serum TSH level below normal (<0.1mIU/L) is one of the main
components of treatment in high risk cases (III, B).
• Patients should be monitored for late side effects of 131I treatment (IV, C).
Surveillance for recurrence of disease is essential and is based on: Annual clinical examination (IV, C).
Annual measurement of serum Tg and TSH (IV, C).
Diagnostic imaging and FNAC when indicated (III, B).

Support and counselling are necessary, particularly in relation to pregnancy (IV, C).
9 Medullary thyroid cancer (section 14)
The initial evaluation of suspected medullary thyroid cancer (MTC) includes FNAC and measurement
of plasma calcitonin (III, B).
The MDT should include or have access to a Clinical Genetics Service and RET gene testing (IV, C).
All patients with MTC should be offered genetic counselling and RET mutation analysis, whether or not
there is an evident family history (IV, C).
RET mutation testing should include exons 10, 11, 13, 14, 15 and 16; screening of exons 10 and 11
alone is an incomplete test (III, B).
Familial MTC represents 25% of all cases of MTC and associated endocrinopathies should be sought
(MEN2A and 2B) (IV, C).
Phaeochromocytoma and primary hyperparathyroidism should be excluded in new patients with MTC,
by measuring 24 hour urine or plasma catecholamines and metanephrines and serum calcium (IV, C).
The minimum treatment is total thyroidectomy and level VI node dissection (III, B).
Prophylactic surgery should be considered in disease-free carriers of germ line RET mutations. Surgery
should be performed in MEN2A patients before the age of 5 years (III, B). MTC occurs early in
MEN2B and is particularly aggressive; thyroid surgery should be performed ideally by the age of 12
months. In children from FMTC kindred, surgery can be postponed until after 10 years of age.
Life-long follow-up is essential and includes monitoring of the tumour marker calcitonin (III, B).
1. Introduction

1.1 The need for guidelines

In spite of advances in diagnostic methods, surgical techniques, and clinical care, differences in survival of patients with thyroid cancer are evident in different countries and the outcome in the UK prior to 1989 appeared to be worse than other western European nations. The reasons for this are unclear and may be multifactorial. It is hoped that the establishment of national guidelines for thyroid cancer, and their implementation through local protocols, would lead to better care, and subsequent improvement in survival for patients with thyroid cancer in England and Wales. 1.2 Aim of the guidelines

The intention is to provide guidance for all those who are involved in the management of patients with differentiated thyroid cancer. This document is not intended as a guideline for the investigation of thyroid nodules. A summary of the key recommendations for the management of adult differentiated and medullary thyroid cancer is provided (previous section ). Randomised trials are often not available in this setting. Therefore, evidence is based on large retrospective studies and the level of evidence according to AHCPR 3,4 is largely II-IV. The three main aims of the guidelines are: • To improve the long-term overall and disease-free survival of patients with thyroid cancer • To enhance the health-related quality of life of patients with thyroid cancer • To improve the referral pattern and management of patients with thyroid cancer 1.3 Incidence

The incidence of thyroid cancer appears to be increasing slowly. In the period 1971-1995 the annual UK incidence was reported at 2.3 per 100,000 women and 0.9 per 100,000 men, with approximately 900 new cases and 250 deaths recorded in England and Wales due to thyroid cancer every year. In 2001 data from Cancer Research UK showed 1200 new cases in England and Wales, with a reported annual incidence for the UK of 3.5 per 100,000 women and 1.3 per 100,000 men.Thyroid cancer is the commonest malignant endocrine tumour, but represents only about 1% of all malignancies7.
1.4 Prognostic
The long-term outcome of patients treated effectively for differentiated thyroid cancer is usually favourable. The overall ten-year survival rate for middle aged adults with differentiated thyroid carcinoma is 80 - 90%. However, 5 - 20% of patients develop local or regional recurrences and 10 - 15% distant metastases. Nine percent of patients with a diagnosis of thyroid cancer die of their disease.9 It is important to assess risk in patients with DTC using a prognostic scoring system: this enables a more accurate prognosis to be given and the appropriate treatment decisions to be made. Any of the staging methodologies (TNM, AMES, MACIS, EORTC, AGES) can be used to assign patients to the high-risk or low-risk band, based on well-established prognostic factors (detailed below). TNM and MACIS probably yield the most useful prognostic information 10,11. Low-risk patients are defined for the purpose of these guidelines as those in the TNM (5th edition)10,12 stage I category, who have a probability of long-term survival greater then 98%. The principal factors contributing to high-risk are older age, male gender, poorly differentiated histological features, tumour size, extrathyroidal invasion and metastatic spread. Treatment also influences prognosis 13.
Age at the time of diagnosis is one of the most consistent prognostic factors in patients with papillary and
follicular thyroid cancer. The risk of recurrence and death increases with age, particularly after the age of
40 years 13-18. Young children, under the age of 10 years, are at higher risk of recurrence than older children
or adolescents 19,20.
The male gender has been reported as an independent risk factor in some but not all studies9,16,17,,21.
The prognosis of papillary thyroid cancer is better than follicular thyroid cancer, however if the
confounding effects of age and extent of tumour at diagnosis are removed, survival rates are
comparable13,16,22-24. Within the papillary thyroid cancer group poorer prognosis is associated with specific
histological types 25-28 and the degree of cellular differentiation and vascular invasion14,29. "Widely
invasive" and "vascular invasion" are features of follicular cancers associated with a poorer prognosis 28,30.
Poorly differentiated follicular cancers (insular carcinoma) and Hürthle cell carcinomas are also associated
with a poorer outcome 16,17,31.
Tumour extent
The risk of recurrence and mortality correlates with the size of the primary tumour 13,15-18,21,31.
Extrathyroidal invasion 13,15-18,29, 32,33, lymph node metastases13,16,17,31, and distant metastases 32,34-36 are all
important prognostic factors.
Prognostic scoring systems for differentiated thyroid cancer
The 5th edition of the TNM classification is recommended10,12,12a,12b (III, B). The MACIS scoring system is
also useful in assessing risk 29.

The TNM system
Primary tumour

pT1 Intrathyroidal
≤ 1cm in greatest dimension Intrathyroidal tumour, >1cm to 4cm in greatest dimension Intrathyroidal tumour, > 4cm in greatest dimension Tumour of any size, extending beyond thyroid capsule Primary tumour cannot be assessed Regional lymph nodes (cervical or upper mediastinal) N0 No nodes involved Regional nodes involved If possible, subdivide Ipsilateral cervical nodes Bilateral, midline or contralateral cervical nodes or mediastinal nodes Nodes cannot be assessed Distant metastases M0 No distant metastases Distant metastases cannot be assessed Papillary or follicular carcinoma Under 45 years 45 years and older Any T, any N, M0 Any T, any N, M1 Any pT, any N, M1
Undifferentiated or anaplastic: all are Stage IV


10 year cancer-specific mortality for differentiated (papillary or
follicular) thyroid cancer 10
MACIS scoring system
3.1 (if <38 years) or 0.08 x age (if >39 years) +0.3 x tumour size (in cm) +1 if incompletely resected +1 if locally invasive +3 if distant metastases present MACIS Score29
20 year disease-specific mortality

1.5 Public health and prevention

Nuclear fall-out is a well-recognised cause of an increase in the risk of thyroid cancer in children. Following the Chernobyl accident the incidence of thyroid cancer rose several hundred times in children in the region. Therapeutic and diagnostic X-rays in childhood are also possible causes of thyroid cancer in adults, and limiting exposure to these sources should be undertaken whenever possible. In cases of populations or individuals being contaminated with 131I, the thyroid can be protected by administering potassium iodide (http://www.arsac.org.uk/notes_for_guidence/index.htm) 37,38.
1.6 Screening

At present there is no screening programme to detect thyroid cancer for the general population. Screening is possible for familial medullary thyroid cancers associated with specific oncogene mutations. The genetic basis of papillary, follicular and anaplastic thyroid cancer has been investigated and, the roles and potential prognostic value of several genes e.g. RET, TRK, ras, BRAF and p53, identified. Testing for these genes is not routinely available in clinical practice.39 The following are considered to be risk factors for thyroid cancer 20,40-48. • History of neck irradiation in childhood • Endemic goitre • Hashimoto's thyroiditis (risk of lymphoma) • Family or personal history of thyroid adenoma • Cowden's syndrome (macrocephaly, mild learning difficulties, carpet-pile tongue, with benign or malignant breast disease) • Familial adenomatous polyposis
• Familial thyroid cancer
While screening generally is not possible, a family history for thyroid cancer should be taken in each case
and if there is a strong familial incidence of thyroid cancer, or association with other cancers, genetic
advice should be considered in appropriate cases from the Regional Genetics Service (IV, C).
2. Presentation, diagnosis and referral

Thyroid nodules are common in adults and may be detected by palpation in 10% of women and 2% of
men49. The prevalence may be as high as 50% or more if using sensitive imaging such as
ultrasonography. The vast majority of thyroid nodules are benign and do not require urgent referral.
Furthermore, thyroid cancer is uncommon in patients who are not euthyroid, and assessment of
biochemical thyroid status is useful in deciding on the referral pathway by the primary care physician (See
also section 16 – A Guide for the Primary Care Physician).
Cancer waiting times
Referrals for suspected cancer are required to be seen in secondary care within 2 weeks50. Specialists in
secondary care have a maximum of 31 days from ‘decision to treat' to first definitive treatment and a
maximum of two month (62 day) wait from urgent GP referral for suspected cancer to first definitive
treatment (Figure 1).
Deadline for first clinic attendance
Cancer waiting times.

In the case of thyroid nodules, the time of ‘decision to treat' is the time a decision to proceed to
thyroidectomy is made on the basis of a cytology result of Thy 3, Thy 4 or Thy 5 (section 3). The date of
first definitive treatment is the date of thyroidectomy (either lobectomy or total thyroidectomy).
The commonest presentation of thyroid cancer is a newly discovered palpable thyroid nodule or increase
in size of a pre-existing nodule. However the vast majority of patients (95%) presenting in this manner
have benign disease. Furthermore the prognosis in those who harbour a malignancy is generally excellent.
The Thyroid Cancer Guidelines Update Group recommends that thyroid nodules need not be referred
under the 2 week cancer rule unless there are suspicious clinical features (section 2.1) and that
optimum care can be delivered by adopting a target of 4 weeks from referral to first assessment in
secondary care, for the remaining cases (IV, C).

Hospitals providing secondary care for patients with suspected thyroid cancer, should develop well
defined and streamlined pathways of referral and care (IV, C). Appropriately resourced designated
diagnostic clinics for patients with thyroid lumps are desirable.
2.1 Symptoms or signs that warrant investigation

Thyroid nodules and goitre are common and often noted coincidentally when patients are being imaged for
other reasons. The vast majority (95%) of cases have benign disease. Primary care physicians must
exercise common sense in selecting which cases should be referred and with what degree of urgency.

Patients with thyroid nodules who may be managed in primary care (IV, C):

Patients with a history of a nodule or goitre which has not changed for years and in the absence of other worrying features (adult patient, no history of neck irradiation, no family history of thyroid cancer, no palpable cervical lymphadenopathy). Patients with a non-palpable asymptomatic nodule discovered coincidentally by imaging of the neck without other worrying features.
Patients that should be referred non-urgently (IV, C):
Patients with nodules who have abnormal thyroid function tests (thyroid cancer is very rare in this group), should be referred to an endocrinologist Patients with a history of sudden onset of pain in a thyroid lump (likely to have bled into a benign thyroid cyst). Thyroid lump -newly presenting or increasing in size over months.
Symptoms needing urgent referral50 (2 week rule) (IV, C):

Unexplained hoarseness or voice changes associated with a goitre. Thyroid nodule in a child Cervical lymphadenopathy associated with a thyroid lump (usually deep cervical or supraclavicular region). A rapidly enlarging painless thyroid mass over a period of weeks (a rare presentation of thyroid cancer and usually associated with anaplastic thyroid cancer or thyroid lymphoma).
Symptoms needing immediate (same day) referral (IV, C):
Stridor associated with a thyroid lump
2.2 Physical

The patient should have a full examination focussing on inspection and palpation of the neck, including
the region of the thyroid, the deep cervical nodes and all other node groups in the neck, particularly the
supraclavicular nodes. The pulse and blood pressure should be recorded (IV, C).

2.3 Appropriate
pending hospital appointment
Thyroid function tests should be requested by the GP (IV, C).
Euthyroid patients with a thyroid nodule may have thyroid cancer and should be referred to a
member of the Multi-Disciplinary Thyroid Cancer Team (section 2.4) (IV, C).
Patients with hyper- or hypothyroidism and a nodular goitre without suspicious features, should be
referred routinely to an endocrinologist (IV, C).
Initiation of other investigations by the GP, such as ultrasonography or isotope scanning, is likely
to result in unnecessary delay in making the diagnosis of cancer 52 and is not recommended (IIb,

2.4 Who to refer to?

Patients should be referred to a surgeon, endocrinologist, clinical oncologist or nuclear medicine
physician who has a specialist interest in thyroid cancer and is a member of the MDT (see
recommendation 1, Key Recommendations)1 (IV, C).
The local Cancer Centre or Cancer Unit5 should provide clear guidance on referral pathways to
General Practitioners (IV, C).
2.5 The role of the multidisciplinary team

All patients with differentiated thyroid cancer should be seen within a multidisciplinary team (MDT) framework as required by the NHS Cancer Services Standards 1,51. Patients will usually be seen initially by an individual member of the MDT, who will be working
according to Guidelines (IV, C).
The treatment plan and care of each newly diagnosed patient should be discussed and supervised by a
core team (physician and surgeon) in consultation with other members of the MDT. This discussion
should be recorded in the patient's records (IV, C).
Close communication between members of the MDT is key for delivering optimal care and a combined clinic is the preferred format. The management of MTC is best delivered by a dedicated group of clinicians within the MDT, with
special expertise in this complex disease (IV, C).

2.6 Hospital Investigations

Essential Assessments

i.Thyroid Function Tests 52 (IIb, B)
ii.FNAC with or without ultrasound scan guidance,53,54 (IIb,B)
iii.Note that the measurement of serum Tg before thyroidectomy has no diagnostic or prognostic value and should not be undertaken55 (III, B).

Other assessments

A number of other investigations may be undertaken, but these are not routinely indicated.
Thyroid autoantibodies may be measured if there is a suspicion of concurrent autoimmune thyroid disease (lymphoma of the thyroid occurs almost exclusively in the presence of Hashimoto's thyroiditis). MR or CT scanning are indicated when the limits of the goitre cannot be determined clinically or for
fixed tumours, or in patients with haemoptysis. It is important to avoid the use of iodinated contrast
media when undertaking CT scans as these may reduce the subsequent radioiodine uptake by thyroid
tissue. Gadolinium enhanced MRI may provide useful information without compromising subsequent
radioiodine uptake by any remaining thyroid tissue. Ultrasound scanning is rarely diagnostic, but may
be of value in aiding FNAC and in the evaluation of co-existing non-dominant nodules as well as any
cervical lymphadenopathy54.
Basal plasma calcitonin levels may be useful if MTC is suspected 56,57 but is not recommended routinely for all thyroid nodules at present (IV, C).
Flow-volume loop studies may be indicated if upper airways obstruction is suspected 58.
Radioisotope studies are usually non-diagnostic for thyroid cancer and therefore of limited value
particularly in iodine-replete countries 59,60.
Excisional biopsy is rarely indicated and when tissue diagnosis prior to intervention is difficult to obtain by FNAC, and would alter patient management (typically when lymphoma is suspected), core biopsy with or without ultrasound guidance is recommended (IV, C).
2.7 Communicating the diagnosis

Informing the primary care team
i. The GP should be informed (by telephone or fax) within 24 hours51 of the diagnosis of cancer being communicated to the patient for the first time, and should be made aware of the
information which has been given to the patient and of the planned treatment (IV, C).
ii. Subsequently any alterations in prognosis, management or drug treatment should be communicated
promptly (IV, C).
Informing the patient
The patient should be informed of the diagnosis of cancer by a member of the MDT; facilities should
be available for this to be done during a private, uninterrupted consultation (IV, C).
A trained nurse specialist should be available to provide additional counselling if required (IV, C).
Whenever possible a relative or friend should attend the consultation and accompany the patient home
(IV, C).
Written information concerning thyroid cancer and its treatment and possible complications should be
available to the patient (Appendix 5) (IV, C).
A prognosis should not be offered before adequate staging information is available (IV, C).
Patients may have difficulty assimilating all this information at a single consultation and an
opportunity for further explanation/discussion should be offered (IV, C).
3. Fine needle aspiration cytology
3.1 Aspiration cytology of thyroid
The clinical usefulness of FNAC depends on obtaining adequate material for diagnosis, which requires close
cooperation between biomedical scientists, pathologists and clinicians managing the patients so that appropriate
procedures are set up, carried out and monitored.
FNAC should be used in the planning of surgery 70-72 (III, B). The diagnosis of thyroid malignancy should
not be made by on FNAC alone. In many cases an operative procedure will be required to establish a
diagnosis of malignancy. Ideally, procedures should be in place to allow adequacy of the sample to be
assessed at the time of aspiration and for material to be retained for ancillary tests if necessary.
ii. Thyroid cytology should be reported by a cytopathologist with a special interest in thyroid disease and should be a member of the MDT. There should be correlation between the cytological diagnosis and any
subsequent histology (IV, C).
iii. Aspiration may be performed by a cytopathologist, endocrinologist, surgeon, nuclear medicine physician, oncologist or radiologist with expertise and interest in thyroid disease. However, he/she should be trained
in good practice and should perform sufficient aspirates to maintain expertise and his/her performance
should be monitored (IV, C). FNAC can readily be carried out without ultrasound guidance if the lesion is
palpable. In many centres there is a move towards the use of ultrasound guidance as this increases
confidence that the lesion has been appropriately sampled. Care must be taken to avoid contamination of
the samples with ultrasound gel when it is used.
iv. All requests should include full clinical details and details of the aspiration procedure, including the site of the abnormality and the site of sampling (IV, C).
v. Where cysts are aspirated the pathologist should be informed whether or not there was complete resolution of the mass after aspiration. All the material aspirated (not just a sample) should be sent to the laboratory
without fixation (and therefore without delay) as tumours may present as cysts (IV, C). Any residual mass
should be immediately reaspirated and the specimens identified separately (IV, C). Cysts can be reported
along the lines outlined below, but the stipulation regarding adequacy can be relaxed where a cyst aspirate
has resulted in resolution of the mass.
vi. The descriptive report will inform the clinical decisions on management, but many centres find it useful to add a numerical coding, such as that defined below (section 3.2). This helps both in guiding discussion on further management and in audit. vii. In some instances, particularly for the diagnosis of malignancy, ancillary tests are required to complete the cytological diagnosis. This requires appropriate material to be retained at the time of the FNA and is
facilitated by the attendance of laboratory staff at the procedure. Immediate assessment of the cytology
allows a decision whether immunocytochemistry, molecular analysis or flow cytometry is required.
Liquid-based cytology is used in some labs but does not allow for either immediate assessment or flow
cytometry and is not the preferred method for immunocytochemistry in all centres. Liquid-based cytology
may be a useful adjunct to direct smears. Where appropriate, the results of additional investigations should
be included in the text of the report. eg. immunopositivity for calcitonin in medullary carcinoma;
immunocytochemistry, FACS analysis or molecular analysis of light chain (κ or λ) restriction in
lymphoma (IV, C).
viii. FNAC can also be used in the diagnosis of suspicious lymph nodes (with the same requirements for assessing adequacy as for thyroid). ix. All cases with suspected or definitive diagnosis of neoplasia, or in whom there are discrepancies between clinical or radiological findings and cytology diagnosis should be discussed at the multidisciplinary
meeting (IV, C).

3.2 Diagnostic Categories

As noted in above (3.1 vi), these should only be used alongside the final cytology assessment after a text report. -Non-diagnostic (inadequate or where technical artefact precludes interpretation; adequate smears usually contain six or more groups of greater than 10 thyroid follicular cells, but the balance between cellularity and colloid is more important). -FNAC should be repeated. Ultrasound guidance may permit more targeted sampling where the initial FNAC has been undertaken by palpation. Cysts containing colloid or histiocytes only, in the absence of epithelial cells, should be classified as Thy1 but should be clearly described as cysts. If the cyst has been aspirated to dryness with no residual mass, clinical/ultrasound follow up alone may be sufficient. -Non-neoplastic (with the descriptive report documenting the features consistent with a colloid nodule or thyroiditis). Cysts may be classified as Thy2 if benign epithelial cells are present. -Two non-neoplastic results 3-6 months apart are generally advisable to exclude neoplasia 61,62, however there are frequent cases where a reliable multi-disciplinary benign diagnosis can be achieved with a single well targetted aspirate. In high clinical risk group cases, the decision to procede to lobectomy may be made even with a benign FNAC diagnosis. (i) Follicular lesion / suspected follicular neoplasm. While some of these will be tumours, many will be shown to be hyperplastic nodules on surgical excision. The descriptive text will indicate the level of suspicion of neoplasia. Most of these patients should be treated by surgical removal of the lobe containing the
nodule 61,62 (III, B). Completion thyroidectomy may be necessary if the histology proves
malignant. In some cases (based on clinical or radiological features) it will be more
appropriate to observe if this decision is supported by the MDT.

(ii) There may be a very small number of other cases where the cytological findings
warrant inclusion in this category rather than Thy2 or Thy4 (eg. worrying features but
cells too scanty to qualify for Thy4, repeat FNA advised). The text of the report should
indicate the worrying findings (IV, C).
These cases should be discussed in the MDT to decide on the appropriate course of action
(IV, C).
Suspicious of malignancy (suspicious, but not diagnostic, of papillary, medullary, anaplastic carcinoma or lymphoma). Surgical intervention indicated for suspected cancer 61,62 (IIb, B). Where Thy4 assessment
has been given because of the absence of material for immunocytochemistry (medullary
carcinoma) or flow cytometry (lymphoma), the aspirate should be repeated. These cases
should be discussed at MDMs before deciding on management. (IV, B).
Diagnostic of malignancy (unequivocal features of papillary, medullary, anaplastic carcinoma, lymphoma or metastatic tumour) The diagnosis should be discussed at the MDT meeting where further management should
be agreed (IV, C). Surgical intervention indicated for differentiated thyroid cancer and
MTC 61,62 (IIb, B), depending on tumour size, clinical stage and other risk factors such as
gender and extremes of age. Indication for appropriate further investigation, radiotherapy
and/or chemotherapy for anaplastic thyroid carcinoma, lymphoma, or metastatic tumour.
4. Primary treatment of differentiated thyroid

4.1 Timescale

Patients with suspected thyroid cancer should normally be seen within two weeks (section 2) (IV, C).
If there are progressive/severe respiratory problems associated with a thyroid mass, patients must be
referred and seen without delay (IV, C).
Patients with new onset of stridor and a thyroid mass must be assessed as emergency cases (IV, C).
Decisions should be made promptly with respect to diagnosis and treatment (maximum 31 days from
diagnosis to first treatment and 62 days from urgent referral to first treatment (section 2, Figure 1) (IV,
131I ablation should be offered within 3-8 weeks after surgery13 (IV, C).

4.2 Staging and risk assignment

Patients should be staged using the TNM classification (section 1.4), and assigned to the
appropriate risk group (section 1.4) (III, B).
Low-risk patients are defined in section 1.4.
4.3 Documentation
The following should be recorded in the notes (IV, C):
• Family history • Date of surgery • Surgeon, assistant, anaesthetist • Extent of surgery • Complications of surgery • The presence or absence of metastases including number and location of lymph nodes • FNAC, histology and pTNM staging • Curative or palliative intent • Date of 131I ablation / therapy • Dose of 131I ablation / therapy and side effects • Follow-up arrangements 5. Surgery for differentiated thyroid cancer

The relationship between volume of thyroid surgery by individual surgeons and outcome is
complex 63,64. However, there is a strong case for patients with thyroid cancer to be operated on
and treated by clinicians who have appropriate training and experience.
The MDT will decide in consultation with the national bodies such as BATES, BAOHL-NS and
specialist groups of the Royal Colleges, the TSG of the Cancer Network, who are to be the
surgical and non-surgical specialists involved in the management of thyroid cancer (IV, C).
A number of compliance measures recommended by the Manual of Cancer Services relate to
thyroid cancer surgery and include a named surgeon to perform lymph node resection and
complex surgical procedures to be preformed in the same hospital of the MDM
Regular audit of outcomes and complications of surgery undertaken by the MDT will help
clinicians to maintain their skill and professional development.
5.1 Preparation for surgery

A hospital providing therapeutic surgery for patients with thyroid cancer should have a nominated
surgeon who will be a member of the MDT with specific training in and experience of thyroid
oncology 1 (IV, C). Membership of the BATES, mandates annual returns and provides comparative
performance data on surgical numbers and outcome measures.
Informed consent should be obtained from all patients after full discussion; the operating surgeon
should normally obtain the consent (IV, C).
The specific complications of thyroid surgery should be discussed as well as those complications
which can occur in any surgical procedure; this should be recorded in the notes. Information sheets for
the patient are recommended (Appendix 5) (IV, C).
The use of prophylactic heparin preparations is not required for routine use in patients undergoing
thyroid surgery (IV,C). Thromboembolism prophylaxis should be used in all cases in the form of
graduated compression hose (TED stockings) and peri-operative calf compression devices 65 (Ia, A).
In patients with suspected or proven thyroid cancer assessment of vocal cord function is strongly
recommended prior to surgery66 (IV, C).
Pre-operative cross-sectional imaging with CT (without contrast) or MRI may be indicated if there is bulky disease or vocal cord paralysis66. Ultrasonography of the neck before thyroid surgery may be valuable in planning surgery, depending on individual surgeon's preference and availability of ultrasonographic expertise67. 5.2 Elective surgical treatment for thyroid cancer
5.2.1 Thyroid surgery

The mainstay of treatment for DTC is surgery 9, 13, 68-70 . Compliance with appropriate and clear definitions of surgical procedures is essential. A diagnostic thyroid FNAC (Thy 5) enables treatment to be planned and discussed with the patient prior to surgery 71-73. The following terms should be used (IV, C):
a. Lobectomy: the complete removal of one thyroid lobe including the isthmus. b. Near-total lobectomy: a total lobectomy leaving behind only the smallest amount of thyroid tissue (significantly less than 1g) to protect the recurrent laryngeal nerves. c. Near-total thyroidectomy: the complete removal of one thyroid lobe (lobectomy) with a near-total lobectomy on the contralateral side or, a bilateral near-total procedure. This should be clearly defined in the operation note. d. Total thyroidectomy: the removal of both thyroid lobes, isthmus and pyramidal lobe e. The terms "subtotal lobectomy" and "subtotal thyroidectomy" are imprecise and should be avoided. The classically described subtotal lobectomy or subtotal thyroidectomy procedures are
inappropriate for the treatment of thyroid cancer. If a total thyroidectomy is not carried out the
surgeon should document the exact extent of surgery to each lobe (IV, C).
ii. The recurrent laryngeal nerve/s should be identified and preserved in virtually all instances (IV, C).
Permanent damage to a recurrent laryngeal nerve should occur in significantly less than 5% of patients
who have undergone surgery for thyroid cancer. Bilateral injuries are extremely rare. Nerve injury rates
are higher after re-operative surgery71.
iii. Infiltration by tumour contributes to recurrent laryngeal nerve palsy rates in malignant disease. In benign disease and in small thyroid cancers (ie in the absence of recurrent laryngeal nerve infiltration)
total thyroidectomy is associated with no higher risk of nerve injury than in lesser procedures, provided
the nerves are identified74.
iv. Attempts should be made to preserve the external branch of the superior laryngeal nerves by ligation of the superior thyroid vessels at the capsule of the gland (IV, C). External laryngeal nerve injury has an
associated morbidity, particularly in voice quality changes. Injury rates may be higher than for
recurrent laryngeal nerve damage 75,76.
Parathyroid glands should whenever possible be identified and preserved (IV, C). If their vascular
supply is compromised then the gland/s should be excised and reimplanted into muscle 77(III, B).
vi. Lymph node dissection in the central compartment (level VI) is associated with an increased risk of postoperative hypoparathyroidism 78,79.
5.2.2 Lymph Node Surgery
The following terms for lymph node groups and surgery should be used (IV, C):
Lateral compartment of neck
Levels I -Submental and submandibular nodes II -Deep cervical chain nodes from the skull base to the level of the hyoid. Further divided by their relationship to the accessory nerve - 2a (medial) and 2b (lateral) III -Deep cervical chain nodes from the level of the hyoid to the level of the cricoid. IV -Deep cervical chain nodes from the level of the cricoid to the suprasternal notch V -Posterior triangle nodes. Can be divided by their relationship to the omohyoid muscle into Va (above) and Vb (below) Central compartment of neck
Level VI -Pre and paratracheal nodes from the hyoid bone superiorly to the level of the sternal notch inferiorly, laterally to the carotid arteries. Mediastinal nodes
Level VII -Superior mediastinal nodes as far as the superior aspect of the brachiocephalic vein Compartment 480

-Lymph nodes between the brachiocephalic vein and tracheal bifurcation within the anterior and posterior mediastinum Selective neck dissection
Any type of cervical lymphadenectomy which involves less than dissection of levels I-V where the spinal accessory nerve (SAN), the internal jugular vein (IJV) and sternocleidomastoid muscle (SCM) are preserved. The levels of node dissection should be clearly recorded. Radical neck dissection
Radical neck dissections are very rarely indicated in the treatment of thyroid cancer but are defined here to ensure accuracy of nomenclature: A classical radical neck dissection removes all of the lymphatic tissue in levels
I-V along with the SAN, SCM and IJV. Extended neck dissection is defined as removal of one or more additional
lymph node groups such as parapharyngeal, superior mediastinal, and paratracheal nodes and / or non-lymphatic structures (digastric muscle, skin). Modified radical neck dissection (MRND) involves removal of lymph nodes in levels 1 - V
with preservation of one or more non lymphatic structures as follows:-
-MRND Type I - Excision of all lymph nodes routinely removed by radical neck dissection with preservation of the SAN. -MRND Type II - Excision of all lymph nodes routinely removed by radical neck dissection with preservation of the SAN and IJV. -MRND Type III (Functional or comprehensive neck dissection) -Excision of all lymph nodes routinely removed by radical neck dissection with preservation of the SAN, IJV, and SCM. In most cases deciding on the type of surgery to be offered is straightforward and only requires
endorsement by the MDT. In other complex cases the MDT must offer guidance on the basis of
the individual patient's cytology and circumstances.
5.2.3 Surgery for papillary carcinoma

Patients with a node negative cancer of 1 cm diameter or less (pT1, section 13.4) can be adequately
treated by lobectomy followed by levothyroxine therapy (section 8.3) 9, 60,64, 69,70,73 (III, B).
For most patients, especially those with tumours greater than 1 cm, multifocal disease, extra-thyroidal
spread, familial disease and those with clinically involved nodes, total thyroidectomy is indicated 13,23
(III, B). Total thyroidectomy is also indicated where there is a history of previous neck irradiation in
childhood (IV, C).
iii. If the diagnosis of thyroid cancer has been made after thyroid lobectomy and completion (contralateral) thyroid lobectomy is required, the latter should be offered within 8 weeks of histological
diagnosis of cancer (IV, C).
iv. Lobectomy alone may be appropriate treatment for some patients with tumours larger then 1 cm if the MDT judges that the risk of recurrence is low (IV, C).
In patients with clinically uninvolved nodes but deemed high-risk (ie any of the following features:
male sex, age > 45 years, tumours greater than 4 cm in diameter, extracapsular or extrathyroidal
disease), total thyroidectomy and level VI node dissection should be performed67,71 (IV, C).
Palpable disease in level VI nodes discovered at surgery is treated by a level VI node dissection. When
suspicious / clinically involved nodes are apparent preoperatively or are encountered at surgery in the
lateral neck, and confirmed by needle biopsy or frozen section then a selective neck dissection (levels
IIa-Vb) is recommended, preserving the accessory nerve, sternocleidomastoid muscle and internal
jugular vein28 (IV, C).

5.2.4 Surgery for follicular carcinoma

i. FNAC cannot at present distinguish follicular adenoma or benign hyperplastic nodules from carcinoma 66,62,81 (IV, C). Thy3 cytology usually mandates lobectomy as the least surgical procedure, although in
some cases (identified by the descriptive report or by the specific clinical scenario) discussion at the
MDT before deciding on an appropriate course of action may be indicated (section 3.1).

ii. Frozen section examination is unhelpful when the FNAC diagnosis is that of a follicular lesion (Thy
3)81 (IV, C).
iii. If definitive histology reveals a follicular adenoma or a hyperplastic nodule, no further treatment is required (III, B).

iv. A follicular carcinoma under 1 cm with minimally invasive features should be treated by lobectomy
(section 8.3)69,70,73 (IV, C).
iv. Patients with follicular cancer showing evidence of vascular invasion should be treated with total thyroidectomy (IV, C).
v. Patients with follicular carcinoma more than 4 cm in diameter should be treated with near-total or total thyroidectomy (C).
vi. Low risk patients (females patients <45 years of age) tumours measuring <2cm in size may be managed by lobectomy alone and levothyroxine therapy following MDT discussion and informed consent 70,82,83
(III, B).
vii. Clear recommendations for otherwise low risk patients with tumours 2 - 4 cm cannot be made. Treatment should be at the discretion of the MDT. viii. Palpable / suspicious cervical lymph nodes are dealt with in a similar manner to papillary carcinoma (sections 5.2.3v, 5.2.3vi)9.13,70 (IV, C).
ix. If the diagnosis of thyroid cancer has been made after thyroid lobectomy and completion (contralateral) thyroid lobectomy is required, the latter should be offered within 8 weeks of histological
diagnosis of cancer (IV, C).

5.2.5 Surgery for oncocytic (Hürthle cell) carcinoma
Malignant Hürthle cell tumours (oncocytic or oxyphil) may behave more aggressively71,84, than other
histological types of differentiated thyroid cancer. Hürthle cell tumours are less likely to concentrate 131I and
total thyroidectomy should be considered.
5.2.6 Surgery for papillary or follicular microcarcinoma
Differentiated thyroid cancers which are less than 1 cm in diameter have an extremely low risk of death from
thyroid cancer (0.1%) 18,85,86 and can therefore be treated adequately by thyroid lobectomy (III, B) provided:
• They do not extend beyond the thyroid capsule • There is no evidence of metastases • There is no evidence of vascular invasion • There is no evidence of multifocality • There is no evidence of contralateral disease 5.3 Emergency surgery

It is rare for emergency surgery to be needed. Usually a careful work up of patients is achievable.
Acute presentation of a patient with thyroid cancer and severe airway compromise requires
urgent/immediate surgery (IV, C).
5.4 Surgery for locally advanced disease

When preoperative vocal cord examination has revealed no sign of recurrent laryngeal nerve
involvement every attempt should be made to dissect the tumour from the nerve/s (IV, C). In patients
with unilateral nerve involvement associated with extensive extrathyroidal disease, the nerve may have
to be sacrificed to achieve a curative procedure.
It may not be possible to remove the entire tumour without damaging both recurrent laryngeal nerves. A
small residue of tumour may be left behind to protect the nerve/s and be subsequently dealt with by 131I
ablation and TSH suppression with levothyroxine (section 8.3), with or without external beam
radiotherapy (section 7)74.
In individual patients with locally advanced disease involving the upper aero-digestive tract and/or one
or both recurrent laryngeal nerves, curative excisional surgery of the tracheal wall and/or oesophagus
should be considered (IV, C).
When radical curative surgery is not possible or agreed to by the patient, treatment with radical
radiotherapy and 131I should be considered (IV, C).

5.5 Early post-surgical management of differentiated thyroid cancer

After total / near-total thyroidectomy patients should be started on triiodothyronine (IV, C). Normal
adult dosage is triiodothyronine 20 mcg tds. This should be stopped for two weeks before either a
radioiodine scan or 131I ablation of thyroid remnant (IV, C).
Serum calcium should be checked within 24 hours of surgery. If hypocalcaemia is detected then it
should be treated as indicated in section 8.2 (III, B).
A baseline post-operative serum Tg should be checked, preferably no earlier than 6 weeks after surgery 55,87-91 (III, B).
5.6 Medullary thyroid cancer
The management of medullary thyroid cancer is discussed in section 14. 5.7 Surgical Management of other rare malignancies of the thyroid

Thyroid lymphoma
Primary thyroid lymphomas occur on a background of Hashimoto's thyroiditis in the vast majority of cases. A clinical diagnosis or high index of suspicion of lymphoma should lead to FNAC and core biopsy. Incision biopsy is not essential for the diagnosis of lymphoma 92 (III, B).
Thyroidectomy is not indicated 93(III, B).
The treatment of choice is chemotherapy followed by radiotherapy or radiotherapy alone. Most cases are high grade B cell lymphoma. Some are MALT (mucosa associated lymphoid tissue) tumours. Prognosis is generally excellent. Patients should be referred to an MDT specialising in lymphoma management (IV, C).

Anaplastic thyroid cancer

This has a very poor prognosis94. Where the diagnosis has not been possible on FNAC, core biopsy may assist the diagnosis.
Surgery is rarely indicated. In a very small subgroup of cases chemo/radiotherapy and surgery may achieve a slightly longer period of survival 94-96 (III, B).
131I ablation or therapy has no place (III, B).
External beam radiotherapy is the mainstay of treatment with or without chemotherapy 94,96 (III, B).
6. Radioiodine ablation and therapy for
differentiated thyroid cancer
Following a total or near-total thyroidectomy, some radioiodine uptake is usually demonstrable in the thyroid bed. 131I destruction of this residual thyroid tissue is known as "radioiodine remnant ablation". "Radioiodine therapy" refers to administration of 131I with the intention to treat recurrent or metastatic disease. The principles and procedures are similar for the administration of 131I for ablation or therapy purposes; the latter is discussed further in section 9.1.
6.1 Preparation for 131I ablation or therapy

The patient should be seen by an appropriate member of the MDT (ARSAC Certificate holder),
preferably in a combined clinic (key recommendation 1 iii), for assessment and full discussion about
radioiodine studies and treatment. Informed consent must be obtained from the patient before
treatment (IV, C).
Patients should adopt a low iodine diet for two weeks prior to 131I and other sources of excess iodine
should be eliminated (eg amiodarone therapy, or recent CT scan with contrast material), (Appendix 5,
patient information leaflet 3) 97-100(III, B).
131I ablation and therapy must only be given in centres suitably equipped and certified for the purpose
(www.ipem.org.uk/publications/IRR99.html) (IV, C).
If 131I can be administered within 3-4 weeks of thyroidectomy, no thyroid hormone replacement is
required in the interim period. This would usually allow TSH to rise to >30 mIU/L at the time of
ablation. For most centres however the interval between thyroidectomy and 131I ablation will be longer.
In these circumstances, patients should start triiodothyronine 20 mcg tds following surgery and this
should be stopped 2 weeks before planned ablation to allow the serum TSH to rise >30mIU/L (IV, C).
A pre-ablation scan is not indicated routinely. If there is doubt about completeness of surgery, a pre-
ablation scan can be performed to assess remnant size. In such cases 123I or 99m Tc-pertechnate may be
preferable to 131I, in order to reduce the risk of stunning 101,102. Demonstration of large thyroid remnants
should lead to consideration of further surgery before 131I ablation 103 (III, B).
Pregnancy must be excluded before 131I ablation or therapy (IV, C).
Breast feeding must be discontinued at least 4 weeks and preferably 8 weeks before 131I ablation or
therapy (IV, C). Breastfeeding should not resume.
Pre-treatment sperm banking should be considered in male patients likely to have more than two high
dose 131I therapy doses104,105 (IV, C). Adequate hydration at the time of treatment and for several days
afterwards helps to prevent a decrease in sperm count.
6.2 Post-operative 131I ablation

The 2002 edition of this guideline recommended that most patients with differentiated thyroid cancer
greater 1-1.5 cm in diameter, should receive 131I ablation. This was based on several retrospective
studies 13,32,36,106-108, including a large cohort study with long follow up13, which showed that patients
older than 45 years with tumours > 1.5 cm had reduced local and distant recurrence and cancer death
rates after remnant 131I ablation. This recommendation (III, IV, B, C) remains largely valid, however
recent evidence suggests that the benefit of 131I ablation for low risk (section 1.4) patients may be
questionable 109,110.
Furthermore, recent data indicate that the incidence of a second malignancy after radioiodine might be
higher than previously thought 111,112. In the light of these findings the MDT decision about 131I
ablation should be individualised and selective (IV, C).
Factors other than size of tumour (such as presence of metastases, completeness of excision, age,
degree of invasion, associated co-morbidities) should be taken into account (IV, C).
Patients should be counselled so that they understand the rationale for 131I ablation (IV, C).
The benefits of 131ablation include: • Eradication of all thyroid cells including potential destruction of residual post-operative microscopic disease and thus possible reduced risk of local and distant tumour recurrence. • Reassurance to patients imparted by the knowledge that serum Tg is undetectable and iodine scan negative, implying that all thyroid tissue is destroyed. • Possible prolonged survival 13,32. • Increased sensitivity of monitoring by serum thyroglobulin measurements and possibly earlier detection of recurrent or metastatic disease9,113. The acute and late side effects of radioiodine (also see section 6.4) should be discussed with the patient (IV, C),
particularly stressing:
• Moderate risk of a dry mouth and sialadenitis • Very small risk of second malignancies. Whenever possible the patient should make an informed decision based on the above risks and benefits (IV, C).
In the absence of randomised trials, recommendations on 131I ablation have to be based on retrospective studies 1,13,32,36,107,108, 114 and recent consensus statements70,83:
A. No indication for 131I ablation (low risk of recurrence or cancer-specific mortality) (IV, C).
Patients should satisfy all of the criteria below for 131I ablation to be omitted.

• Complete surgery. • Favourable histology. • Tumour unifocal, < 1cm in diameter, N0, M0, or minimally invasive follicular thyroid cancers, without vascular invasion smaller than 2cm in diameter 82,83. • No extension beyond the thyroid capsule.
B. Definite indications (IV, C).
Any of the following criteria constitute an indication for 131I ablation

• Distant metastases • Incomplete tumour resection • Complete tumour resection but high risk of recurrence or mortality (tumour extension beyond the thyroid capsule, or more than 10 involved lymph nodes and more than 3 lymph nodes with extracapsular spread 113.
C. Probable indications (IV, C).
The list of indications below applies to patients that do not fall under categories A and B above. Any
one of the following categories is a "probable" indication for 131I ablation.

• Less than total thyroidectomy (inferred from operation notes, or pathology report , or when an ultrasound scan or isotope scan show a significant post-operative thyroid remnant). • Status of lymph nodes not assessed at surgery (section 5.2) • Tumour size >1 cm and <4 cm • Tumours <1 cm in diameter with unfavourable histology (tall-cell, columnar-cell or diffuse sclerosing papillary cancers, widely invasive or poorly differentiated follicular cancers) • Multifocal tumours <1 cm: this is controversial 13,114. Activity of 131I for ablation The present recommendation for remnant ablation is 3.7 GBq pending the results of ongoing
trials 115,116 (III, B).
For patients with known metastases, higher 131I activities (5-7.4 MBq) 117 are often used. Procedure for remnant ablation with 131I Information leaflets (Appendix 5) and support from the specialist nurse should be provided (IV, C).
Serum TSH and Tg should be measured immediately prior to 131I administration (IV, C).
be performed where indicated, immediately prior to 131I administration and the result should be negative (IV, C).
The serum TSH should be greater than 30 mIU/L at the time of ablation (see 6.1.iv) (IV, C).
rhTSH has recently been licensed for use with remnant ablation after total or near-total thyroidectomy,
based on a randomised controlled trial in low risk (section 1.4) patients118. RhTSH may also be used for
ablation in cases where thyroxine withdrawal is contraindicated or ineffective in raising the serum
TSH. Discussion of such cases by the MDT is recommended (IV, C). The protocol consists of 0.9 mg
rhTSH administered intramuscularly on two consecutive days followed by 3.7GBq of 131I ablation 24
hours after the second rhTSH injection.
Aftercare following 131I ablation After admission for 131I ablation, ward procedures should be followed and the patient discharged only
after Medical Physics assessment. Written advice about restricting the extent of contact between the
paitent and otheres should be handed to the patient before discharge (IV, C). At the time of discharge
(usually 3 days after 131I), thyroid hormone treatment (normally levothyroxine) should be commenced
and a letter must go to the GP with the patient (IV, C).
A post-ablation scan should be performed 3-10 days after the 131I dose 119 (III, B).
Patients should be reviewed (preferably in a combined clinic) after 2-3 months for assessment,
adjustment of TSH suppressive dose of levothyroxine, and to make arrangements for follow-up Tg
measurement and scanning (IV, C).

6.3 Diagnostic scan (131I 74 to 150 MBq)98,120

131I diagnostic scan after 131I ablation Diagnostic scans (see 6.3.3) are carried out in order to assess the effectiveness of ablation and requirement
for further 131I therapy 121.
Recent data indicate that low risk (section 1.4) cases may be assessed adequately by measuring serum Tg
(in the absence of Tg assay interference) under conditions of TSH stimulation, without the need for a
radioiodine scan, which rarely provides additional helpful information in such cases 121-124. In low risk
cases therefore the diagnostic scan may be omitted, although TSH stimulated serum Tg should be assessed.
If a diagnostic scan is omitted, ultrasonography of the neck is a valuable alternative in assessing local
recurrence (section 8.5).
A diagnostic radioiodine scan (in conjunction with stimulated serum Tg measurement) should be
performed in all other cases 121 (III, B).
6.3.1 Indications for repeat diagnostic scans after radioiodine ablation
Patients with high-risk disease and with Tg antibodies interfering with serum Tg measurements, may need additional radioiodine, ultrasound or other cross-sectional (eg CT or MRI) scans (section 8.5). No further diagnostic radioiodine scans are required for other groups of patients, unless there are
indications of disease progression, such as a rising serum Tg, clinical or radiological evidence of
progression (section 8.5). In such cases scans should be performed after thyroid hormone withdrawal
rather than rhTSH unless there are clear contraindications to thyroid hormone withdrawal (further
discussed in section 8.5) (III, B).
6.3.2 Precautions i. Pregnancy: ARSAC recommends a minimum period of 6 months before conception for females, as the absorbed dose to the foetus should not exceed 1mGy125 (III, C). If pregnancy is deferred for at least 6
months after high dose 131I ablation or therapy to the mother, there is no risk to fertility or normal
pregnancy, though there is a slightly increased risk of miscarriage if pregnancy occurs within one year
of high dose 131I 126-129 (III, B).
ii. In males a 4 month period of avoidance of fathering a child is recommended 125 (IV, C).
6.3.3 Timing of radioiodine diagnostic scans Diagnostic radioiodine scans usually are scheduled not earlier than 6 months after 131I ablation. In selected
cases (patients with aggressive disease), this should be brought forward to 4 months119 (IV, C).
6.3.4 Procedure
i. Before a diagnostic radioiodine scan, patients should switch from levothyroxine to triiodothyronine replacement (triiodothyronine 20 mcg tid). Levothyroxine is routinely stopped four weeks, and
triiodothyronine two weeks before the diagnostic scan (IV, C).
ii. The serum TSH and Tg should be measured on the day of the diagnostic scan and before the tracer dose of radioiodine is administered. A serum TSH >30 mIU/L is essential for optimal imaging (IV, C).
iii. If abnormal uptake of the tracer is detectable, further 131I therapy (usually 3.7 - 5.5 GBq) should be given (IV, C). A post-treatment scan should be performed 3-10 days later, as it is a significantly more
sensitive procedure than a diagnostic radioiodine scan employing a small (74-150 MBq) activity of 131I
119 (section 9), (III, B).
iv. Patients should restart levothyroxine when the scan has been reported and the report discussed with the patient. The dose of levothyroxine is the same as prior to the diagnostic scan. Levothyroxine should
not be restarted earlier than 3 days after the diagnostic radioiodine scan. Caution should be exercised
when recommencing levothyroxine in patients with vascular disease (IV, C).
v. A low iodine diet should be advised before diagnostic radioiodine scans (and 131I ablation or therapy) (section 6.1,iii and Appendix 5 patient information leaflet 3 (III, B).
vi. Patients should have access to the clinic, the ward where iodine treatment was given, specialist nurse or the clinician's secretary (IV, C).
6.4 Short-term and long-term side effects of 131I ablation and therapy

The main side-effect is transient hypothyroidism, unless rhTSH is used 118, 123,130 (section 6.2).
Possible early effects
• Abnormality of taste and sialadenitis minimised by good hydration. • Nausea (minimised by antiemetics). • Neck discomfort and swelling within a few days of radioiodine can occur rarely. It is more common when a large thyroid remnant is present. Simple analgesics should be tried initially. A short course of steroids may be necessary in severe cases. • Radiation cystitis, radiation gastritis, bleeding into secondary deposits and oedema in cerebral secondary deposits are all extremely rare after administered activities of 3 GBq or less 100,104,113. Possible late effects
• Dry mouth and abnormal taste. • Sialadenitis and lachrymal gland dysfunction. • Lifetime incidence of leukaemia and second cancers is low, of the order of 0.5%100, 131-133. Of
3 cohort studies only 1 showed an increased but non-significant risk of leukaemia (relative risk about 2). The risk of leukaemia increases with a high cumulative dose (greater than 18.5 GBq) and with use of additional external beam radiotherapy. Patients who have high cumulative dose of 131I may also be more likely to develop second malignancies (for example bladder, and possibly colorectal, breast and salivary glands) 111, 112,131. The total cumulative activity should therefore be kept as low as possible 106,107,131-136. • Radiation fibrosis can occur in patients who have had diffuse pulmonary metastatic disease and have received repeated doses of 131I 136-138. • Increased risk of miscarriage may persist for up to 1 year after 131I ablation / therapy 126-129. • Infertility in men 104,105 7. External beam radiotherapy
Post operative adjuvant external beam radiotherapy is infrequently indicated for differentiated thyroid cancer. It probably reduces local recurrence in patients at high risk due to residual disease, where further surgery is not appropriate 96,139,140. Radiotherapy should be planned carefully, preferably using 3D conformal planning techniques, with appropriate precautions taken for prevention of radiation myelopathy, 15,107,141,142, 143,144,145 (III, B).
Intensity modulated radiotherapy (IMRT) may have advantages over conventionally planned radiotherapy
when treating the thyroid bed and regional nodes. However an important consideration in the adjuvant
setting, is that the use of intensity modulated radiotherapy with multiple fields can theoretically increase
the risk of second malignancies in long term survivors146.

7.1 Adjuvant external beam radiotherapy
The main indications for adjuvant radiotherapy are:
Gross evidence of local tumour invasion at surgery, presumed to have significant macro- or microscopic residual disease, particularly if the residual tumour fails to concentrate sufficient amounts of radioiodine. Extensive pT4 disease in patients older than 60 years of age with extensive extra nodal spread after optimal surgery, even in the absence of evident residual disease 96,108,141,144-146.
7.2 High dose external beam radiotherapy as part of primary treatment
Indicated for (IV, C):

Unresectable tumours that do not concentrate radioactive iodine. Unresectable bulky tumours in addition to radioactive iodine treatment. For palliative radiotherapy, see section 9.2. 8. Post-treatment follow-up

Routine follow-up includes clinical assessment of thyroid status and examination of the neck or other relavant
systems. Abnormal masses in the neck or elsewhere should trigger further investigations including FNAC (IV, C).

8.1 Voice dysfunction
This may result if there is external laryngeal nerve and/or recurrent nerve injury.
Voice dysfunction must be investigated if symptoms persist beyond two weeks after surgery (IV, C).
The patient should be referred to a specialist practitioner who is capable of carrying out direct and/or indirect laryngoscopy (IV, C).
8.2 Management of hypocalcaemia
i. Serum calcium should be checked on the day after surgery, and daily until stable 147,148 (III, B). A decline
in serum calcium concentration in the first 24 hours after surgery is predictive of the need for calcium supplementation 149. ii. If hypocalcaemia develops, commence calcium supplementation at an initial dose of 500mg elemental calcium 3 times daily (III, B). The dose is adjusted as indicated by the response. Occasionally intravenous
calcium gluconate may be required. Mild asymptomatic hypocalcaemia usually does not require treatment,
although monitoring is indicated.
iii. If hypocalcaemia does not improve, or worsens, introduce alfacalcidol (or calcitriol) (III, B).
iv. Close monitoring of serum calcium is needed to prevent hypercalcaemia (IV, C).
v. Monitoring of serum calcium should be supervised in the specialist clinic, with the assistance of the GP if appropriate (IV, C).
vi. After total thyroidectomy, 30% of patients will need calcium supplementation with or without alfacalcidol. By three months less than 10% of patients will still require calcium supplementation150. vii. Hypoparathyroidsm is often transient and a predictor of this is an elevated (or upper normal range) serum PTH concentration at the time of the occurrence of hypocalcaemia150. Thus, the majority of patients on
calcitriol / alfacalcidol l /calcium supplements can have this treatment withdrawn. Supplements should be
slowly and gradually reduced and serum calcium monitored every few months until withdrawn and the
eucalcaemia is restored. The combined effects of hypocalcaemia and hypothyroidism are poorly tolerated
and calcitriol / alfacalcidol / calcium supplement withdrawal should take place during euthyroidism (IV,

viii. If hypoparathyroidism is permanent, the lowest dose of supplements should be adjusted so as to maintain the serum calcium at the lower end of the normal range, while avoiding hypercalciuria. In stable cases
annual measurement of serum calcium is recommended (IV, C).

8.3. Long-term suppression of serum thyrotrophin (TSH)

Levothyroxine should be used in preference to triiodothyronine for long-term suppression 151 (III, B).
The dose of levothyroxine should be sufficient to suppress the TSH to <0.1mIU/L 151-155 (III, B).
The dose of levothyroxine should be adjusted by 25 mcg (about every 6 weeks), until the serum TSH is <0.1
mIU/L) (IV, C). To achieve this, most patients will require 175 or 200 mcg daily.
In patients with low risk (section 1.4) differentiated thyroid cancer, there is some evidence that it may
be adequate to keep the serum TSH to below the reference range in the absence of full TSH
suppression (typically 0.1-0.5 mIU/L) (III, B)151-155, but robust long-term data are not available.

iv. Suppressive levothyroxine therapy is best supervised by a member of the MDT (IV, C), although
alternative arrangements may be appropriate in low risk cases (see section 10 v). The GP should be advised of the reason for this suppression and of the target serum TSH
concentration (IV, C).

8.4 Measurement of serum thyroglobulin (Tg) in long-term follow-up (Appendix 1)
Tg is secreted by both normal and cancerous thyroid cells. In patients who have not had a total thyroidectomy and
131I ablation, the interpretation of serum Tg measurements is limited by the inability to differentiate between
tumour and thyroid remnant 156,157. Detectable serum Tg is highly suggestive of thyroid remnant, residual or
recurrent tumour.
The cut-off serum Tg concentration beyond which recurrent / persistent disease is implied depends on several
variables including the assay employed by each laboratory. Individual laboratories should advise clinicians on the
significance of detectable serum Tg at low concentrations (Appendix 1) (IV, C).
A serum Tg which is rising with time while on suppressive thyroxine therapy is highly suggestive of tumour
recurrence or progression.
Endogenous antibodies to Tg (TgAb) and other unidentified factors may interfere with the measurement of serum
Tg. Measurement of TgAb is valuable in interpreting the serum Tg result, although the absence of TgAb does not
absolutely exclude the possibility of interference with the Tg assay. There is evidence that TgAb measurement may
be of some value in monitoring patients with thyroid cancer 157.
To ensure continuity in monitoring, clinicians should use the same laboratory and Tg assay on a long-
term basis. Laboratories should not change methods without prior consultation with clinical users of
the service (IV, C).
TgAb should be measured by a quantitative method simultaneously with measurement of serum Tg. If
TgAb are detectable, measurement should be repeated at regular ( 6 monthly) intervals. If negative
they should be measured at follow-up when Tg is measured 55 (IV, C).
Samples should not be collected sooner than 6 weeks post-thyroidectomy, or 131I ablation / therapy 55,156-161 (III, C).
There is normally no need to measure serum Tg more frequently than 3 monthly during routine
follow-up; for patients in remission an annual check of serum Tg should be measured while on
suppressive levothyroxine treatment. (IV, C).
Since Tg release is TSH-dependent, serum TSH concentration should be determined concurrently to
aid interpretation. The requesting clinician should indicate on the form whether the patient is on
thyroid hormone therapy and the TSH result should be available to the laboratory performing the Tg
assay (IV, C).

There is no need for TSH stimulation if the basal serum Tg is already detectable. vii. Patients in whom the basal Tg remains persistently detectable (ie while on suppressive levothyroxine therapy), or rises with subsequent assessments, require further evaluation 157 (III,

viii. At routine follow-up most patients should have serum Tg measured while on TSH suppression
TSH stimulated serum Tg measurement
The diagnostic sensitivity of serum Tg measurements is enhanced by an elevated serum TSH concentration
(optimally by serum TSH > 30 mIU/L) 156,157. Tumour recurrence or progression can be detected earlier by
detecting a raised serum Tg after TSH stimulation compared with measurement of Tg on suppressive thyroxine
therapy. Tg should be measured when the serum TSH is more than 30 mIU/L (usually in conjunction with
diagnostic radioiodine scans) (IV, C).
In low risk (section 1.4) patients who have undetectable serum Tg while on suppressive thyroxine therapy,
stimulated serum Tg measurement alone (ie without a concomitant WBS), represents adequate initial follow-up,
provided there is no Tg assay interference 70,122,124. A concomitant WBS in such cases rarely adds valuable
information, although ultrasonography of the neck may be indicated (section 8.5). If serum Tg is undetectable
under TSH stimulation, then in low risk patients subsequent long-term follow-up by measurement of serum Tg
under TSH suppression alone is sufficient 70,122,124 (III, B).
TSH stimulation can be achieved either by thyroid hormone withdrawal (aiming for a serum TSH >30mIU/L,
section 6.3.4 for procedure), or by injections of rhTSH while the patient remains on suppressive thyroxine
therapy. The latter is indicated in selected cases (see below).
TSH-stimulated serum Tg measurements (with or without a radioiodine scan) may be performed 6-8
months after 131I ablation or therapy (IV, C). A single undetectable TSH-stimulated serum Tg in the
absence of assay interference, is highly predictive of no future recurrence provided the Tg can be
measured reliably (ie absence of assay interference) in low risk (section 1.4) patients who have
undergone total or near-total thyroidectomy and 131I ablation 162. The role of neck ultrasonography in
such cases is discussed in section 8.5.
The TSH-stimulated serum Tg may remain detectable at low concentrations after 131I ablation. This
could be indicative of residual / recurrent cancer, but in the majority of cases signifies the presence of
thyroid remnant. An expectant policy in low risk (section 1.4) cases is recommended with repeat TSH-
stimulated Tg assessments at 6-12 month intervals (IV, C). In many cases, repeat assessments will
reveal a gradual decline in stimulated serum Tg to the point of no detection, when routine follow-up
should be resumed.
Patients in whom the stimulated serum Tg remains persistently detectable or rises with subsequent
assessments, require further evaluation (section 9.1) (III, B)

Recommendations for the use of rhTSH-stimulated Tg in routine follow-up
TSH-stimulation for measurement of serum Tg (or for WBS) can be achieved by thyroid hormone withdrawal or by
administration of recombinant human TSH (rhTSH). The suitability of patients for rhTSH should be assessed by the MDT (IV, C).
ii. For the following group of patients rhTSH is the only possible or safe option for diagnostic purposes 163 and for ablation or therapy:
• hypopituitarism • functional metastases causing suppression of serum TSH • severe ischaemic heart disease • previous history of psychiatric disturbance precipitated by hypothyroidism • advanced disease / frailty. iii. Patients should be informed about the advantages and disadvantages of this diagnostic method compared with conventional thyroid hormone withdrawal (IV, C).
iv. In patients known to have anti-Tg antibodies interfering with the Tg assay it is preferable to perform diagnostic radioiodine scans after thyroid hormone withdrawal, rather than with rhTSH as the Tg data may be impossible to
interpret, and WBSs after thyroid hormone withdrawal are more sensitive than after rhTSH administration 123
(III, B).
v. rhTSH is known to cause a transient but significant rise in serum thyroid hormone concentrations if functioning thyroid tissue is present. Therefore, caution should be exercised in patients with large thyroid remnants (IV, C).
iv. rhTSH (two 0.9 mg doses) should be administered by deep IM injection on days 1 and 2 and serum Tg measured on day 5 123 (Ib, A). Due consideration must be given to the practicalities of collecting, handling and analysis of
radioactive samples and advice must be obtained from the relevant radiation, transport and health and safety
authorities (IV, C).
v. rhTSH should not be used if basal (unstimulated) serum Tg is elevated or the patient is expected to have 131I therapy (IV, C).

8.5 Role of imaging by ultrasonography and whole body 131I scanning in routine

After total thyroidectomy and post-operative 131I ablation, diagnostic WBSs have relatively low sensitivity in
detecting residual or recurrent disease, when compared with measurement of serum Tg 122, 123, 124,164. Evidence
supporting a specific adjunctive role for ultrasonography (in addition to routine measurement of serum Tg), or its
utility compared with other modes of follow-up, is presently scanty 67.

Ultrasonography is a sensitive method for detection of residual disease in the thyroid bed and metastatic disease in
lymph nodes; its sensitivity is higher than neck palpation. This technique is used routinely during follow-up in
some centres, especially outside the UK. Ultrasonography may uncommonly suggest the presence of disease in
the absence of a rise in serum Tg and may indicate the site of disease in those with a raised serum Tg.
Ultrasonography may have a particular role when serum Tg measurements are unreliable because of the presence
of assay interference.
A single diagnostic WBS performed 6-8 months (but not sooner than 6 months) after 131I ablation is
generally indicated except in those with low risk (section 1.4) disease (see iii below). If this is
negative, further WBS is not usually required, depending on results of monitoring by measurement of
serum Tg 121 (III, B).

ii. If rhTSH is used for WBS (see 8.4 for indications) the recommended protocol is as follows (Ib, A) 123:
• rhTSH (0.9 mg) should be administered by deep IM injection on days 1 and 2 • a tracing dose of 131I (approximately 150 MBq) should be given on day 3 • the scan should be performed on day 5. A minimum of 30 minutes scanning time or a minimum of 140,000 counts per minute should be obtained • serum Tg is also measured on day 5. iii. Low risk patients (section 1.4), who have been shown to have undetectable stimulated serum Tg in the absence of assay interference, do not require routine diagnostic WBS during follow-up if the serum Tg
on suppressive levothyroxine therapy remains undetectable. In such cases ultrasonography of the neck
6-12 months after thyroidectomy is indicated 122, 123, 124,164 (III, B).
iv Patients who are likely to require 131I therapy should have a WBS under conventional thyroid hormone withdrawal. This includes patients with detectable serum Tg, known thyroid remnant or known
metastatic disease (IV, C).
9. Recurrent / persistent differentiated thyroid
Early detection of recurrent disease can lead to cure or certainly long-term survival, particularly if it is
operable or takes up radioactive iodine 9,13, 69,70,87,106, 113, 142, 143,165. Distant metastases develop in 5-23% of
patients with differentiated thyroid carcinoma, mainly in the lungs and bones.
Detection of abnormal masses in the neck or elsewhere should lead to FNAC and other appropriate
investigations (IV, C).

9.1 Recurrence in the thyroid bed or cervical lymph nodes
Surgical re-exploration is the preferred method of management, usually followed by 131I therapy 68,107 (III,
). Recurrent neck disease uncontrolled by surgery and 131I therapy is best treated by high dose palliative
external beam radiotherapy (section 9.7). As patients are likely to survive for a significant period, radical
external beam radiotherapy (doses 50 – 66Gy) is often necessary with a daily fractionation and meticulous
radiotherapy planning techniques 96,139.
While the strategy outlined above is applicable in high risk cases, the efficacy of an aggressive approach in
low risk cases where sensitive diagnostic techniques (high definition ultrasonography, stimulated serum
thyroglobulin measurements) indicate very low volume disease in the neck, is less well established.

9.2 Metastatic disease involving lung and other soft tissue areas
These sites of metastases are usually not amenable to surgery and should be treated with 131I 13, 100,136,166,167
(III, B). If the tumour takes up radioiodine, long-term survival is possible. The preferred treatment is
repeated doses of 131I; activities ranging from 3.7-10.1 GBq at 3-9 month intervals have been employed,
with the usual being 5.5 GBq given every 4-6 months 142,98,136, 166,167. Late side effects of 131I therapy are
minimised if intervals between treatments are no less than 6-12 months. While empirical doses are
generally used, dosimetric assessment has been also helpful in certain studies 96,167-169.
• Pulmonary fibrosis following treatment with 131I for diffuse pulmonary metastases has been reported rarely. It can be avoided or minimised by using a lung activity, which is less than 2.96GBq (80 mCi) 48 hours after administration 168. There is no maximum limit to the cumulative 131I dose that can be given to patients with persistent disease 136. A normal blood count must be confirmed prior to each 131I therapy administration and impairment of
renal function would demand a lower dose 142 (IV, C).
A WBS 3-10 days after 131I administration provides better scintigraphic assessment of disease than a diagnostic scan and response to treatment although this has been questioned 119. 9.3 Bone metastases
Extensive bony metastases are generally not curable by 131I therapy alone. For solitary or limited number of bony metastases that are not cured by 131I therapy, external beam radiotherapy with / without resection and / or embolisation should be considered in selected cases. External beam radiotherapy also has a very important role in the management of spinal cord compression for vertebral metastases in addition to surgery 9.4 Cerebral metastases
External beam radiotherapy has an important palliative role in the management of cerebral metastases along with surgery if appropriate 96.
9.5 Other Metastatic sites
In selected cases when there are a limited number of metastases, metastasectomy or radiofrequency ablation may also be helpful.
9.6 Unknown metastatic sites
For patients with rising serum Tg (section 8.4) and a negative diagnostic radioiodine scan
the following is recommended 170 (III, B):

Ensure that the diagnostic 131I scan is truly negative rather than falsely positive Tg (eg suboptimal serum TSH elevation). Ensure that the thyroglobulin measurement is reliable and that there is no interference particularly by heterophil antibodies 171. Check for possible iodine contamination (eg amiodarone therapy, or recent CT scan with contrast material). The management of patients with a rising serum Tg and negative diagnostic radioiodine scan needs to be tailored to the individual after discussion in the MDT. There are three potential approaches: a) No action until the patient becomes symptomatic. b) Additional investigations aiming to localise the disease recurrence and offer specific c) Empirical use of 131I therapy 9,170,172,173. If option (b) is judged to be appropriate the following investigations are recommended: Neck ultrasound (with or without FNAC), or cervico-mediastinal MRI scan should be performed, as
the commonest sites of recurrence are the thyroid bed and cervical and mediastinal lymph nodes 124,164
(III, B).
If (i) is negative, a CT scan of the lungs should be done to exclude micronodular lung metastases (IV,

If (ii) is negative, then bony secondary deposits should be excluded, either by 99mTc bisphosphonate
scan or, if indicated, other imaging agents like 99mTc MIBI (IV, C).
If the above are all negative, consider scanning with 18FDG-PET, 201Thallium or 99mTc Tetrofosmin,
to exclude potentially operable disease. 18FDG-PET scanning has a higher sensitivity for detecting
dedifferentiating recurrent disease but at present is only available in selected centres in the UK 174-178
Thyroxine withdrawal 175 and rhTSH administration179 have been shown to increase the sensitivity of
18FDG-PET scan. Patients with positive 18FDG-PET scan have been shown to have a markedly reduced 3 year survival compared with 18FDG-PET scan negative patients 174. 18FDG-PET scan may reveal recurrent disease, which is operable. If the recurrent disease is not operable then consideration should be given to high dose palliative external beam radiotherapy. 111In Octreotide imaging may be positive in some Tg positive iodine scan negative patients 180. Data for the use of therapy with radiolabelled somatostatin analogues in patients with Hürthle cell carcinoma and dedifferentiated papillary carcinoma are limited 181. If all the above are still negative, therapeutic 131I may be considered if the Tg continues to rise. Other factors that should be considered in making this decision include the risk category of the patient and the rate of rise of the serum Tg concentration 182. In such cases a post-treatment scan (3-10 days after 131I therapy) should be included, as previously undetected metastases may then be visible. A recent
metaanalysis of published studies confirms that 50% of post-therapy scans performed with ‘blind'
therapy will be positive and a fall in Tg levels will subsequently be observed in 60% of patients with
positive post-therapy scans172. The usual dose of 131I is 3-5.5 GBq. The decision to treat should be
taken by the MDT with the full informed consent of patient and consideration of the potential risks
and benefits of the treatment in the absence of prospective randomised studies 83,183 (IV, C).
The combination of a positive diagnostic radioiodine scan and an undetectable serum Tg is very rare.
In such cases the possibility of false positivity should be adequately explored before administering
further 131I therapy184 (III, B).

9.7 Palliative care

Palliative care is not necessary in the vast majority of patients with differentiated thyroid cancer because
they are cured. However, in a very small proportion of patients with recurrent end-stage disease (and in
patients with anaplastic thyroid cancer) specialist palliative care help would be necessary. A consultant
in palliative medicine should liaise with the MDT and patients requiring palliative care patients should be
referred early to the local palliative care team185 (IV, C).
High dose palliative external beam radiotherapy may be appropriate in good performance status patients with
anticipated survival of greater than six months. External beam radiotherapy also has a role in palliation of
symptoms from fungating lymph nodes, bleeding tumour, stridor, superior vena caval obstruction along and

Stridor and fear of choking are very distressing and can also be alleviated by pharmacological means,
palliative surgery and counselling.
Palliative chemotherapy
Palliative chemotherapy may have a role in end-stage disease uncontrolled by surgery, 131I therapy or
external beam radiotherapy. The agents used are doxorubicin and cisplatinum, but durable responses are
uncommon 186,187. Chemotherapy should be used only in patients with progressive and symptomatic
disease (IV, C). Concurrent chemo/radiotherapy has been tried, particularly in anaplastic carcinoma,
with some very short-term benefits 68,134,188,189. New treatments are coming on line based upon an
emerging understanding of the pathobiology of the disease. Agents that target different pathways are
being developed and evaluated in clinical trials, and it may be appropriate to offer a patient with
advanced disease the opportunity of participating in such a trial.
10. Long-term follow-up of differentiated thyroid
Regular follow-up is necessary particularly for detection of early recurrence, initiation of appropriate
treatment, TSH suppression and management of hypocalcaemia. This can be undertaken by a member
of the MDT, working in a multidisciplinary setting and according to the established local guidelines
(IV, C).
Once the thyroid remnant has been ablated the frequency of attendance will be decided in each case
individually: usually 3-6 monthly for the first 2 years, decreasing to 6-8 monthly for 3 years, and
annually thereafter (IV, C).
Support and counselling may be necessary, particularly for younger patients, and in relation to pregnancy. Follow up should be life-long (IV, C) because:-
• The disease has a long natural history.
• Late recurrences can occur, which can be successfully treated with a view to cure or long term • The consequences of supraphysiological levothyroxine replacement (such as atrial fibrillation and osteoporosis) need monitoring especially as the patient ages. • Late side effects of 131I treatment may develop, such as leukaemia or second tumours. Low-risk cases who have completed their treatment, shown to be free of disease at 5 years and are no longer judged to require TSH suppression, may be followed up in settings other than the multi-disciplinary thyroid cancer clinic. This may include a nurse-led clinic or in primary care following agreement of well defined protocols and re-referral pathways. At each visit the following tasks should be completed (IV, C):
Clinical examination Assessment of adequacy of TSH suppression and of possible effects of thyrotoxicosis Measurement of Tg as a marker of tumour recurrence. Tg antibodies should be measured simultaneously with measurement of Tg55. Measurement of serum calcium and PTH if indicated. 11. Pregnancy and thyroid cancer
11.1 Diagnosis

thyroid cancer in pregnancy
The management of thyroid cancer diagnosed during pregnancy requires careful consideration of risks to
mother and foetus. However thyroid cancer discovered during pregnancy does not behave more
aggressively than that diagnosed in a similar aged group of non-pregnant women. Women of
childbearing age with thyroid cancer generally have a good prognosis, similar to that in non-pregnant
women190. Discussion of the case by the MDT, as well as counselling of the couple, are imperative (IV,

Surgery is indicated, but evidence regarding the optimum timing is unclear. Thyroidectomy in the first
trimester of pregnancy carries a high risk of abortion, but may be performed safely in the 2nd trimester.
Alternatively surgery can be deferred until after delivery, provided that the tumour is monitored regularly
(eg by ultrasound) and found to be reasonably stable. In cases of advanced or aggressive disease delays in
treatment would be undesirable, and termination of pregnancy may (rarely) need to be considered.
131I ablation or therapy must be avoided in pregnancy. Suppressive thyroxine therapy is safe during
A thyroid nodule presenting during pregnancy should be investigated by FNAC (IV, C).
Radioiodine scans are contraindicated in pregnancy and breast-feeding (IV, C).
If thyroid cancer is diagnosed or suspected, the following options should be considered (IV, C):
• Defer thyroidectomy, 131I studies and treatment until the post-partum period
• Perform a thyroidectomy during the 2nd trimester of pregnancy, to be followed by suppressive
doses of levothyroxine, but defer the 131I studies until the post-partum period • Termination of pregnancy followed by thyroidectomy and 131I studies and treatment (this option is very rarely necessary). Pregnancy in the treated patient
i. In accordance with ARSAC, it is recommended that women should defer conception for a minimum of 6 months and men for a period of 4 months following 131I ablation or therapy 125 (IV, C). A small risk
of spontaneous abortion may persist for up to 1 year after high dose 131I ablation or therapy
126,127,128,131,190,191 . There is no risk of previous 131I ablation or therapy to the foetus, provided the recommendations are followed 128,191 ii. Suppressive levothyroxine therapy should continue during pregnancy and to achieve this, the dose should be increased as soon as pregnancy is confirmed by approximately 25% 192 and further adjusted
if necessary according to monitoring of thyroid function tests (III, B).
iii. The thyroid status should be checked by measurements of serum TSH and free thyroxine during each trimester to ensure that TSH remains suppressed, as levothyroxine requirements may
increase during pregnancy 55,192 (IIa, B).
iv. For men there should be a minimum period of 4 months from 131I ablation or therapy before unprotected intercourse takes place 125 (IV, C).
12. Thyroid cancer in childhood
Differentiated thyroid cancer is rare in children. Children at particular risk are those previously exposed to radiotherapy to the head or neck. Thyroid nodules are more likely to be malignant in children than in adults so surgical excision may be appropriate even if findings from FNAC suggest benign disease. Thyroid cancer in children aged 10 years or less is more aggressive than in adults and risk of recurrence is higher 193,197. The general principles of management are similar to those in adults, however the managing team must
include a paediatric endocrinologist, paediatric oncologist (or nuclear medicine physician) and nurse
specialist or counsellor (IV, C).
Total thyroidectomy followed by TSH suppression is recommended for most patients 2 (IV, C).
Selective neck dissection is recommended for children with clinically positive neck nodes 195. 131I ablation 2,195-197 is recommended for all children particularly those aged under 10 years, but the
decision about 131I ablation should be individually determined (IV, C).
Follow-up with serial serum Tg measurements should be life-long198 (III, B).
Guidelines for the management of differentiated and medullary thyroid cancer (MTC) in children can be found in reference 2. MTC in children is discussed in section 14. 13. Pathology reporting, grading and staging of
thyroid cancer

13.1 General principles

Pathologists dealing with thyroid tumours should have a special interest in thyroid pathology or participate in
a network with the opportunity of pathology review (IV, C).
Cases should be handled and reported according to the minimum datasets of the Royal College of
)(IV, C).
Many of the features affect staging and prognosis and may therefore influence clinical management decisions. Many of the features affect staging and prognosis and may therefore influence clinical management decisions. A general approach to specimen handling is outlined below. Points specifically relating to medullary carcinoma are discussed in Section 14. Most lesions should have had FNAC before surgery 49, 69 (III, B) (section 3), so at least a differential
diagnosis should be available.
Frozen section may be used to confirm the diagnosis of papillary carcinoma, but should not be used to
differentiate follicular carcinoma from adenoma 199,200 (Ib, A).
In all cases, the blocks taken should be appropriate to make the diagnosis, and to assess the extent of
invasion and the completeness of excision (IV, C).
Follicular lesions that are not grossly invasive should be widely sampled at the interface between the
tumour, the capsule and the normal gland to detect capsular or vascular invasion. Small lesions (≤
30mm in maximum dimension) should be processed in their entirety and 10 blocks should be taken
from larger lesions 30,201 (III, B, IV, C).
Lymph nodes should be carefully dissected, the numbers counted and locations noted if possible (IV,
Ipsilateral, midline and contralateral nodes should be documented separately (IV, C). Formal neck
dissections should be dealt with according to RCPath protocols for head and neck cancers
(http://www.rcpath.org/resources/pdf/HeadNeckDatasetJun05.pdf) (IV, C).
13.2 Gross description (C)
The following features should be included:
• Nature of specimen - lobectomy - right or left; total/near-total or subtotal; +/- isthmus - thyroidectomy - total or near-total - weight and dimensions • Description of lesion(s) - single or multifocal - solid or cystic - dimensions (of largest if multifocal) - encapsulated or not - confined to gland or invading adjacent structures • Lymph nodes - site - number - macroscopic involvement • Presence or absence of parathyroid glands 13.3 Microscopic report (C)
Core data sets for all tumour types
• Type of carcinoma.
• Whether the tumour is a single lesion or is multifocal.
• Maximum dimension of carcinoma.
• Completeness of excision.
• Extension into extrathyroidal tissues (this defines the lesion as pT4).
• The presence and extent of any lymphatic/vascular invasion.
• The site and number of lymph nodes involved.

Additional points for histological subtypes

Typical or variant (specify) Follicular
Angioinvasive or capsule only Minimally invasive or widely invasive Oncocytic (Hürthle cell) follicular carcinoma (At least 75% Hürthle cells)
Report in same manner as follicular.
13.4 Pathological staging

There are a number of classifications in current use for the staging of thyroid cancer202. It is
recommended that at present, pathological staging should be performed on the basis of TNM
classification 202-204 (III, B). This is easy to apply and has been shown in a number of studies to
correlate with outcome 10,196 (section 1.4).
The recommended stratification for age at diagnosis as under 45 years or 45 years and over should be
applied to papillary and follicular tumours (IV, C).
In multifocal lesions, the largest is used for staging purposes (IV, C).

13.5 Staging protocol

See section 1.4.
13.6 Grading of tumours

Papillary carcinomas should have their specific subtype documented (eg. classical, tall cell variant, etc)
(IV, C).
Histological grading of thyroid tumours is not commonly performed and is not included in RCPath
dataset. However, grading may provide useful additional prognostic information 27,205. It is therefore
recommended that, where possible, a grade be assigned to the primary tumour as follows (IV, C):
G1 Well differentiated G2 Moderately well differentiated G3 Poorly differentiated G4 Undifferentiated GX Grade cannot be assessed For papillary tumours, a simple grading system based on a combination of marked nuclear atypia, tumour necrosis and vascular invasion has recently been proposed205. Grade 1 tumours have none of these features, Grade 2 one or more. For follicular tumours, the presence of an insular, solid or other less well-differentiated component in a predominantly follicular lesion would warrant Grade 2. Predominance of the dedifferentiated component would place the tumour in Grade 3. 14. Management of medullary thyroid cancer

MTC is a rare disease (it accounts for 5-10% of all thyroid cancers) that requires a dedicated,
multidisciplinary regional service. All patients with MTC should be referred for surgical treatment to the
Cancer Centre5 (IV, C).
Developments in the molecular genetics of MTC have facilitated a rational framework for management.
The use and interpretation of molecular diagnostics is difficult and requires careful application in
individual patients and their families 206,207.
The biology of MTC has unique implications for the development and structure of clinical services and management of this unusual disease. 25% of MTC is familial, (MEN2A/MEN2B/FMTC) necessitating a comprehensive and integrated approach to both the patient and their family. The familial forms are inherited in an autosomal dominant manner. When MTC arises as part of a familial syndrome, assessment and management of the other endocrine
tumours is required.
Patients may survive for many years even with a significant tumour burden. This makes the risk/benefit decisions for additional intervention for persistent or recurrent disease difficult. Clinical services for MTC should dovetail with those for MEN1 and MEN2, which require similar
services and address common issues (IV, C).

14.1 History

MTC may present with a lump in the neck or metastasis, or dysphagia, or with the systemic effects that result from coincident secretion of calcitonin and other peptides (frequent loose stools and vasomotor flushing). Less commonly, adrenocorticotrophin (ACTH) is secreted. The diagnosis may be made following fine needle aspiration (FNAC) of a thyroid nodule or lymph node, in the absence of previous clinical suspicion. Unsuspected MTC can be found at surgery. In all cases, a comprehensive family history must be taken to include 1st and 2nd degree relatives to
search for features of MTC or other endocrinopathies that may occur in individuals with MEN2. This
includes a history of unexpected sudden death, which should raise the suspicion of occult
phaeochromocytoma 208,209 (IV, C).

14.2 Hospital

Pre-operative investigations should include: A baseline value for calcitonin 55,210,211 (Appendix 1.ii) (III, B).
At least one 24 hour urine sample assayed for catecholamines and metanephrines to exclude
phaeochromocytoma and a serum calcium to exclude hyperparathyroidism 211,212. These tests should
be performed in all MTC patients prior to neck surgery even in the absence of a positive family
history or symptoms (III, B).
RET mutation analysis to establish the possible genetic basis for the disease within an individual or
kindred (III, B).
A stimulation test with calcium/pentagastrin may be indicated to confirm a diagnosis of MTC pre-
operatively in relatives of patients with familial MTC, to exclude the rare causes of false positive
basal calcitonin elevation or when calcitonin levels are only mildly elevated (Appendix 1) 55,213.
Routine preoperative staging of MTC with US / CT / MRI (chest, thorax, abdomen) is not essential prior to first time intervention, as it does not alter the need for neck surgery. These investigations however may provide the surgeon with information to guide the extent of surgery in the central compartment of the neck and superior mediastinum. 14.3 Treatment
Prior to thyroid surgery all patients should be managed as described in Section 5.1.
206-208, 214-217
The aims of first time surgical treatment of MTC are loco-regional control (the neck and superior mediastinum), and in some patients to obtain a biochemical as well as clinical cure. All patients with established MTC should undergo total thyroidectomy and central compartment node dissection with the inferior limit of the dissection being the brachiocephalic vein (levels VI and VII) 218 (III, B).
Patients with pT2 – 4 tumours, or palpable lymph nodes in the central or lateral compartment should in
addition undergo bilateral selective neck dissection of levels IIa – Vb 218 (III, B).
In the absence of direct invasion, the sternomastoid muscle / the internal jugular vein / the accessory
nerve should be conserved. Routine dissection of levels I, IIb and Va is not required unless there are
palpable / suspicious nodes at these sites. The management of recurrent laryngeal nerve
involvement by tumour is described in section 5. When there is strong suspicion or evidence of
mediastinal node involvement below the brachiocephalic vein, the patient should be considered for
further surgery (IV, C). This will require a sternotomy 218.
Patients with distant metastases at presentation often have prolonged survival. Even in the presence of
disseminated disease, surgery (total thyroidectomy and central compartment node dissection) should
be considered to prevent subsequent compromise of the trachea, oesophagus and recurrent laryngeal
nerves. These structures should be preserved whenever possible (IV, C).
Prophylactic surgery should be offered to disease-free carriers of germ line RET mutations, identified
by genetic screening programmes 216,219-221 (III, B). The possibility of future surgery should be
discussed with parents before testing children (IV, C).
In ideal circumstances these patients would be expected to have C-cell hyperplasia (CCH) rather than MTC, but in many cases, by the time of presentation the transition from CCH to MTC will have occurred. It is important to distinguish the need for therapeutic surgery from prophylactic surgery. This will depend upon the genotype, the age of the patient and the basal calcitonin 219,222,223. Children with MEN2B should undergo prophylactic thyroidectomy within the first year of life.
Children with MEN2A should undergo prophylactic thyroidectomy before the age of 5 206,221 (III, B).
In children with MEN2A under the age of 10, it is probably unnecessary to perform lymph node dissection. In older children and those with MEN2B, central compartment lymphadenectomy should probably be performed at the time of thyroidectomy. Gene carriers from FMTC kindred should undergo prophylactic thyroid surgery after the age of 10;
lymph node dissection is not indicated before the age of 20 years 222 (III, B).
Following surgery, voice dysfunction and hypocalcaemia should be managed as described in sections 8.1 and 8.2. Investigation of persistent or increasing hypercalcitoninaemia Post-operative samples should be measured no earlier than 10 days after thyroidectomy55,224 (III, B). Plasma
calcitonin levels are most informative 6 months after surgery 55.
There is good evidence that meticulous initial surgery will reduce the risk of postoperative calcitonin elevation but
high calcitonin levels after surgery are a common finding. This will depend upon the pre-operative basal
calcitonin, the stage of the tumour at presentation and the adequacy of initial surgery 225,226.
True local recurrence is unusual after adequate initial surgery. When initial surgery was incomplete, re-operation
on the neck (lymphadenectomy of the central and/or lateral compartments) with curative intent should be
considered (IV, C).
Mediastinal lymphadenectomy may be necessary when there is a strong suspicion of, or proven nodal disease at
this site.
It is important to distinguish loco-regional, persistent / recurrent disease from distant micro- or macro metastases
as the cause of an elevated calcitonin. Non-invasive imaging (chest and abdominal CT or MRI and cervical and/or
abdominal ultrasound, bone scan should be performed (IV, C) but may not be helpful because of the
morphological pattern of metastatic MTC in lung and liver (i.e. miliary disease). Laparoscopy 227, selective
arteriography228 will in some cases, identify occult hepatic metastases. Other less invasive options to detect
metastatic MTC in patients with rising calcitonin and negative whole body CT or MRI, include Pentavalent 99m Tc-
DMSA, 131 I-MIBG, 111In-Octreotide and 18FDG-PET scans. In general functional isotope studies are most likely to
detect bulk disease.
Re-operative surgery in the neck and mediastinum should be considered even when there are known distant
metastases to prevent the complications of large volume disease affecting the airway, oesophagus or laryngeal
nerves (IV, C).

Radiotherapy and chemotherapy

Routine adjuvant external beam radiotherapy has not been shown to improve survival 229,230 but may improve the relapse free rate if there is gross microscopic residual disease or extensive nodal disease Radiotherapy may control local symptoms in cases of inoperable or secondary disease. Chemotherapy is generally ineffective, but may be tried for progressive and symptomatic disseminated disease 96,186,187,230,231. Radiolabelled somatostatin analogue and / or 131I-MIBG therapy may be useful in a small number of cases 233-235, but have not been evaluated in clinical trials. Alpha-interferon and other new drugs (tyrosine kinase inhibitors) may also have a role, however the evidence base is scanty at present. Genetic immunotherapy may be useful in the treatment of inoperable metastatic disease. The use of suicide gene therapy and tyrosine kinase inhibitors is under investigation 236,237. Treatment with any of these modalities should preferably be within a clinical trial.
Palliative Care
Medical therapy should concentrate on symptom control (IV, C).
Gastrointestinal symptoms often respond well to symptomatic treatment (such as Lomotil and / or codeine phosphate). Somatostatin analogues are a possible alternative which may decrease tumour peptide release.
14.4 Follow-up

Lifelong follow-up is recommended (IV, C):
Response to primary surgery can be assessed clinically, and by the measurement of serum calcitonin
and tumour markers, usually 6 months after surgery 55 (IV, C).
The presence of an elevated but stable calcitonin level post-operatively may be managed
conservatively, provided treatable disease has been excluded radiologically. Progressively rising
levels should trigger imaging for further staging. In the absence of recurrent symptoms, appropriate
follow-up intervals are 6 – 12 months (IV, C).

14.5 Pathology

The general principles for specimen handling and gross description outlined in sections 13.1 and 13.2 should apply
also to cases of medullary carcinoma. However, in cases of intrathyroidal tumour, the whole specimen should be
blocked. Where possible the upper third of the lobe(s) should be sampled and immunostained for calcitonin to
identify C cell hyperplasia (IV, C).
Microscopic report
The general principles of section 13.3 apply. It is recommended that the diagnosis is confirmed by calcitonin
immunoreactivity (IV, C).
The following features should also be noted (IV, C):
Presence of amyloid C cell hyperplasia
Tumour staging

The staging protocols used in section 1.4 should be applied (IV, C). Age is not a prognostic factor in medullary
thyroid cancer.
Medullary carcinoma
Stage I
Any pT, any N, M1
14.6 Molecular
208,221, 238-247
It is important to recognise the heritable form of MTC because of the risk of other tumours in the individual and in the family. Early recognition and prophylactic surgery in MEN2 are effective in reducing both mortality and morbidity. Approximately 25% of MTCs are hereditary, as part of the MEN2 / FMTC syndrome. Lack of family history does not exclude heritable disease. The disease may not be apparent in relatives because of ‘skipped' generations; or an isolated case may be the start of a new family. Inherited MTC without other endocrinopathies also occurs. It is inherited in similar ways but tends to be more indolent than other forms of MTC248. Because of the rarity of MTC and the complexity of genetic investigation and management, cases
should be managed by a specialist clinical service in close liaison with a Regional Genetics Centre
(IV, C).

Genetic investigation of a patient with MTC.

1 Clinical
history suggestive of MEN2 syndrome:
Symptoms/history phaeochromocytoma, parathyroid disease. Features of MEN2B: facies (see Appendix 2), constipation/diarrhoea, presence of mucosal neuromas, medullated corneal nerve fibres, marfanoid habitus, colonic ganglioneuromatosis. (occasionally associated with MEN2). A systematic family history should be taken, to include all first and second degree relatives, with attention
to features suggestive of MEN2 (thyroid, adrenal, parathyroid disease) (IV, C).

The history must be recorded in the case notes (IV, C).

2 Genetic

Before testing: If expertise is not available within the primary clinical team, the patient should be referred to the
Clinical Genetics Service (IV, C).
Because of the possibility of heritable disease, every case of MTC should be offered genetic testing
unless there are good reasons for not undertaking this. (IV, C).
Testing should always begin with the affected individual, if he/she is available (IV, C).
If the affected individual is not available, the decision and strategy for testing should be discussed with
the Clinical Genetics Service (IV, C).
Before blood is taken, a clear explanation must be given of the nature of the test, the possible
outcomes, and of the implications of a positive or negative result for the individual and the family.
This explanation should be recorded in the case notes for each individual (IV, C).
Testing: From the affected individual: ideally 10ml EDTA anticoagulated blood. Tests can be performed on smaller (e.g. 1 to 2ml) amounts of blood, but discuss this with the appropriate NHS genetics laboratory. Send with clinical details and family history to appropriate NHS genetics laboratory. Patients with no special clinical features should be tested first for RET mutations in exons 10 and 11; if
these are negative, for exons 13-16 243-247 (III, B). Failure to screen exons 13-16 is an incomplete test.
Patients with clinical features of MEN2B should be tested first for mutations in codons 918 and 922
(exon 16), 883 (exon 15) and 804 and 806 (exon 14) (IV, C).
Patients with clinical features of Hirschsprung's should be tested first for mutations in codons 609,
611, 618, 620 (exon 10) (IV, C).

Action on results:
If a mutation is found
The result should be communicated, in the clinic, to the patient (IV, C).
Permission must be obtained from the patient to disclose this result to anyone else, including GP and
family (IV, C).
A plan should be made for the management of the individual and for the further investigation of the
family (IV, C).
The individual Mutation implies MEN2 and thus (depending on the site of the mutation) a future risk of other MEN2 components such as further thyroid tumours, adrenal and parathyroid disease. The family Family members at risk should be offered testing for the specific RET mutation (IV, C).
Contacting and investigating the family requires expertise and coordination and should normally be
undertaken by a specialist clinical genetics department, in liaison with the relevant clinical teams (IV,

If no mutation is found

Check with the genetics laboratory that a complete mutation screen has been carried out, to include
exons 10, 11 and 13-16 of the RET gene. If not, ask for this to be completed (IV, C).
If there is strong presumptive evidence from individual or family history of inherited disease: a) discuss further with clinical genetics department and consider research-based search for novel mutations (IV, C).
b) consider biochemical screening of family members at risk using stimulated (I.V. calcium / pentagastrin, Appendix 1) calcitonin testing from age 5 years.
If there is no clinical evidence to suggest inherited disease, the need for stimulated calcitonin screening of family members at risk is unclear. There are a few MEN2 families (mostly with familial MTC only) in which RET mutations have not so far been identified. Thus, a failure to find a RET mutation in an isolated case of MTC cannot completely exclude the possibility of heritable disease. The extent of the remaining risk is very small – around 1% or less, depending on the clinical features of the patient. Young age at onset of the MTC (<35 years) and the presence of C-cell hyperplasia in the thyroid are in favour of inherited disease, but not conclusive; nor does absence of these features exclude it. The correct action in this situation is a matter for clinical judgement and may differ from family to family.
Mutation testing of tumour

If no blood sample is available from the affected individual, DNA may be obtainable from either frozen or paraffin embedded tumour. Interpretation of RET mutations identified from tumour tissue requires care. The mutations may be
either germline or somatic in origin. Specialist genetic advice should be sought (IV, C).
A somatic MEN2B-type (codon 918) mutation is commonly present in sporadic tumours, but may also be present in tumours from MEN2A cases. This finding cannot therefore be used to exclude heritable disease.
14.7 MEN2B

Photographs to aid diagnosis will be found in Appendix 2. MTC occurs early in MEN2B and is particularly
aggressive 211,249.
Any new patient with MTC, especially a child or young adult, should be carefully assessed for clinical
features suggestive of MEN2B 198,209,250,251 (III, B).
The clinical features of MEN2B may be hard to recognise, and is sometimes diagnosed in error. >98% of MEN2B patients reported to date have mutations in either RET codon 918 (95%) or 883
(3%). Unless the clinical evidence is strong, preferably with radiological and/or biopsy support, the
absence of these mutations excludes MEN2B with high probability. Where there is doubt the patient
should be referred for a specialist opinion 251,252 (IV, C).
Child of an MEN2B patient

Because MEN2B can present with clinically significant MTC in the neonatal period, management of
the newborn child of a known MEN2B carrier should be planned in advance with specialist advice
(IV, C).
Because MTC occurs early in MEN2B and is particularly aggressive, thyroid surgery in an affected
child should be done as early as possible, and preferably before the age of 12 months 221 (III, B).
Prenatal testing is possible. Couples who ask about prenatal testing for MEN2 should be referred to a
genetics clinic (IV, C).
15. Registration, core dataset and audit
It is mandatory for all patients with thyroid cancer in England and Wales to be registered within
the Regional Cancer Network.
Further information on core dataset can be found on:
Prospective data collection and regular audit of outcomes and processes should be carried out (IV, C).
The primary purpose is to ensure that all patients are adequately followed up.
The development of a national dataset will allow audit of national outcomes and will provide the potential for
prospective assessment of different treatment modalities. This comprises a thyroid cancer specific dataset
which has been in use at one hospital for the past decade and has undergone serial modifications during that
time. This could be implemented for general use immediately to record treatment and relapse, and to
facilitate audit. Subsequent analysis would then permit improvements in treatment and also setting up of
prospective clinical trials. The NHS Information Authority is developing a generic data set for all cancers;
this is available on the internet and will soon become established.
The proformas should be completed by a member of the MDT (IV, C).
16. Thyroid cancer: a guide for the primary care

16.1 Raising awareness

Thyroid nodules, particularly when solitary and clinically obvious should be investigated, as they carry a small but significant malignant potential (about 10% or less). Cancer of the thyroid is rare representing only about 1% of all cancers. The overall 10-year survival rate for differentiated thyroid carcinoma is 80 - 90%. 5 - 20% of patients develop local or regional recurrences and 10 - 15% develop distant metastases.
16.2 Prevention

Previous head or neck irradiation in childhood is a possible cause of thyroid cancer in adults. Exposure to radiation should be limited whenever possible. Nuclear fall-out is a well recognised cause of increased risk of thyroid cancer. In cases of populations or individuals being contaminated with radioactive iodine, the thyroid can be protected by administering potassium iodide 254,255.
16.3 Screening

General screening – no screening is indicated for the general population.
Risk-directed screening should be considered (by referral to the specialist secondary team) when the primary care
physician identifies patients with:
• Familial thyroid cancer, including medullary thyroid cancer (MTC) • History of neck irradiation in childhood • Family history of multiple endocrine neoplasia type 2 (MEN2) The following carry a statistically increased risk of thyroid malignancy but no screening is recommended: • Endemic goitre • Hashimoto's thyroiditis (risk of lymphoma) • Family or personal history of thyroid adenoma • Cowden's syndrome (macrocephaly, mild learning difficulties, carpet-pile tongue, with benign or malignant breast disease) • Familial adenomatous polyposis
16.4 Diagnosis and referral

The usual presentation is that of a palpable lump in the neck, which moves on swallowing. There may be no other symptoms or signs. Immediate (same day) referrals
Patients with stridor associated with a thyroid swelling should be referred immediately to secondary care
(depending on locally provided facilities this may be the Accident and Emergency Department, Head and
Neck or General Surgical emergency services).
Urgent referrals under the 2 week rule for suspected cancer
The presence of the following symptoms or signs in association with a thyroid swelling may indicate more
aggressive or advanced disease and should be referred urgently under the 2 week rule:
• Unexplained hoarseness or voice change
• Thyroid nodule / goitre in a child • Cervical lymphadenopathy associated with a thyroid lump (usually deep cervical or supraclavicular • A rapidly enlarging painless thyroid mass over a period of weeks (a rare presentation of thyroid cancer and usually associated with anaplastic thyroid cancer or thyroid lymphoma). Patients in whom exclusion of thyroid cancer is required, should be referred to a thyroid nodule clinic, or a surgeon, endocrinologist or nuclear medicine physician who has a specialist interest in thyroid cancer and is a member of the Regional Thyroid Cancer MDT. Non-urgent referrals
• Patients with nodules who have abnormal thyroid function tests (thyroid cancer is very rare in this group), who should be referred to an endocrinologist • Patients with a history of sudden onset of pain in a thyroid lump (likely to have bled into a benign • Thyroid lump -newly presenting or increasing in size over months.
Physical Examination

Examination focusing on inspection and palpation of the thyroid and neck, movement of the nodule with swallowing, and palpation of the deep cervical nodes and all other node groups in the neck especially supraclavicular nodes. ii. Pulse and blood pressure Appropriate investigations pending hospital appointment

Thyroid function tests should be requested by the GP and appended to the referral letter. Hyper– or hypo – thyroidism associated with a nodular goitre is unlikely to be thyroid cancer; these patients should be referred routinely to an endocrinologist. Initiation of other investigations (such as ultrasound scanning or autoantibodies) by the primary care physician are unnecessary and may cause delay in making the diagnosis of cancer. 16.5 Algorithm for diagnosis & management of a thyroid nodule or suspected thyroid cancer in
general practice
Patient presents to GP Examination of neck Thyroid nodule causing and confirmation of No other symptoms or signs Thyroid function Immediate (same day) Unexplained hoarseness or voice change, or patient is a child, or there Routine referral to is cervical lymphadenopathy, or rapidly enlarging painless thyroid mass over a period of weeks Routine referral to specialist Urgent (2 week rule) referral to specialist clinic
** There is no need to arrange ultrasound of thyroid

Communicating the diagnosis

Informing the primary care team

The GP should be informed within 24 hours (by telephone or fax) of the diagnosis being communicated to the patient for the first time and should be made aware of the information which has been given to the patient and of the planned treatment. Subsequent alterations in prognosis, management or drug treatment should be communicated promptly.
Informing the patient

The patient should be informed of the diagnosis by a member of the specialist team. A trained nurse specialist should be available in the specialist clinic to provide additional counselling if required. Whenever possible a relative or friend should attend the hospital consultation and accompany the patient home. Written information concerning thyroid cancer and its treatment should be available to the patient in the specialist clinic. A prognosis will not be offered before adequate staging information is available.
vi. Patients may have difficulty understanding all this information at a single consultation and an
opportunity for further explanation/discussion will be offered.
Summary of treatment of thyroid cancer

Treatment decisions will be made by the Thyroid Cancer MDT, who will continue to supervise the patient's care. Patients will commonly undergo thyroidectomy, followed in some cases by an ablative dose of radioiodine (131I). Thereafter patients will generally require thyroxine to suppress TSH to <0.1 mu/l, and some will need treatment to correct hypocalcaemia. Scans and/or measurement of serum thyroglobulin (Tg) will be performed at regular intervals to detect possible recurrence. Patients will be provided with written and verbal information about the disease and its management. v. Pregnancy: radioiodine is not given to pregnant patients. Pregnancy must be avoided for 6
months after 131I ablation or therapy in women men and 4 months in men. Breastfeeding needs to be stopped at least 4 weeks and preferably 8 weeks before radioiodine ablation or therapy and not be resumed.
16.6 Follow up

Follow-up of patients with thyroid cancer is life-long and usually supervised by specialists in
secondary or tertiary care, who are members of the MDT. Low-risk cases who have completed their

treatment, shown to be free of disease at 5 years and no longer judged to require TSH suppression,
may be followed up in settings other than the multi-disciplinary thyroid cancer clinic. This may be a
nurse led clinic or in primary care following agreement of well defined protocols and re-referral

i Thyroxine treatment: The dose of levothyroxine will be higher than a normal replacement dose, as it
is intended to suppress the level of serum TSH to undetectable. For example if the TSH is in the
normal range the dose of levothyroxine will usually be increased. Suppressive levothyroxine therapy
is best supervised by a member of the thyroid cancer MDT. The GP will be advised of the target
levels of TSH.

ii. Treatment of hypocalcaemia: Patients taking calcitriol / alfacalcidol and /or calcium supplements
must be monitored closely (for example every 3 months if generally stable, more frequently if not) to ensure that hypercalcaemia does not occur. The dose is kept to the minimum required to maintain serum calcium in the (low) normal range. Changes to the dose will usually be by 250 ng (0.25 µg).
iii. The GP should ensure that the patient knows about and is offered:
MDT follow up – necessary for detection of early recurrence and complications and for
their appropriate treatment.
Access to a member of the core team for support.
Appendix 1. Assay methodology
Many differentiated papillary and follicular carcinomas of the thyroid synthesise and
secrete Tg. Detailed UK guidelines for measurements of relevant anlytes have been published 55, and will be
summarised here. Problems with Tg assays have been widely reviewed 55,124,156,157,256,257.
There should be clear guidance from each laboratory to its users on specimen requirements and
sample stability (IV, C)
The use of the Community Bureau of Reference standard for Tg (CRM 457) is recommended.
(IV, C).
The use of a reference range derived from normal subjects is not recommended. The laboratory
should ensure that users are aware that patients on levothyroxine suppressive therapy should
ideally have an undetectable serum Tg 55 (IV, C).
Laboratories and manufacturers should determine and quote the minimum detection limit (MDL)
of their assay based on functional sensitivity derived from patient samples. The MDL should
ideally be ≤ 0.2µg/L (IV, C).
Although a post-rhTSH serum Tg of >2 µg/L has been suggested as a positive response justifying
further investigations and treatment, this threshold may not be applicable for many of the
currently available assays because of known differences in sensitivity, accuracy and precision (IV,

Laboratories and manufacturers should identify the analytical range of their Tg assay and adopt
procedures to identify samples suffering from ‘hook' effects (IV, C).
Laboratories and manufacturers should inform clinicians of the possibility of interference due to
endogenous TgAb and indicate the most likely nature of the interference (false elevation/false
reduction in measured Tg) (IV, C).
Identification of possible assay interference is best achieved using either TgAb measurements or
discordance between Tg results obtained using immunometric assay and radioimmunoassay257.
Recovery experiments alone are not recommended to identify assay interference256 (IV, C).
Tg autoantibodies should be measured in the same sample as serum Tg. The presence of Tg
autoantibodies usually invalidates the serum Tg result but interference may also occur in the
absence of Tg antibodies. If Tg autoantibodies are to be measured a sensitive immunoassay rather
than a haemagluttination method should be used55 (IV, C).
For a particular Tg method it is highly desirable that the results of a clinical assessment of the
assay performance should be available. The clinical sensitivity and specificity (i.e. positive and
negative predictive values) of the assays should be quoted (IV, C).
Laboratories should run internal quality control samples, which encompass the range of results
reported by the laboratory. A sample with a Tg concentration close to the minimum detection
limit (MDL) should also be run with each assay to ensure that the quoted MDL is being achieved
(IV, C).
Laboratories should participate in an accredited External Quality Assessment scheme (IV, C).
Requesting clinicians should contact the laboratory before the collection of blood for Tg/TSH
from patients post radioiodine administration (IV, C). The handling and transport of such
radioactive samples is covered by legislation and such samples may not be accepted by the


The following recommendations apply to the measurement of calcitonin (IV, C):
Timing of specimen collection

Ideally a fasting morning specimen should be obtained to enable optimal comparison with reference values. If this is not possible, specimens can be collected at any time of day. Post-operative samples should be collected at least ten days after thyroidectomy and should also
be fasting samples if possible 55,224 (III, B).
For provocative testing samples are usually collected 5 minutes prior to administration of calcium /pentagastrin and then at intervals of 2, 5 and 7-10 minutes after 213. Indications for provocative testing are listed in 14.2 iv.
Type of specimen

Serum or plasma requirements should be confirmed with laboratories and/or manufacturers' kit
inserts. The effect of gel tubes should be known (IV, C).
Calcitonin results may be affected by visible haemolysis or lipaemia and assay of such specimens should be avoided if possible
Specimen stability
Calcitonin in serum or plasma is unstable and blood specimens should be kept on ice. Red cells should then
be separated within 30 minutes of collection and serum or plasma frozen immediately (IV, C).
Effects of other conditions, treatment and medication

Previous treatment with monoclonal antibodies should be noted because of the potential for
interference with human anti-mouse antibodies in immunometric assays (IV, C).
Chronic renal failure may increase basal calcitonin levels. Mildly increased calcitonin may be observed in pregnancy, pernicious anemia, autoimmune thyroid disease, hypergastrinaemia and during the neonatal period.

Assays should be standardised using WHO International Standard IS 89/620 (IV, C).
Laboratories must decide whether to use a method that recognises primarily monomeric calcitonin
(immunometric) or a method with broader specificity (RIA) (IV, C).

Assay sensitivity
Laboratories and/or manufacturers should determine and quote the minimum detection limit of their assay
based on precision profiles derived from patient samples (IV, C).
Assay interferences
Laboratories should have established protocols for identifying specimens that may have ‘hooked' and
specimens that may contain interfering antibodies (IV, C).
Clinical assessment
For a particular calcitonin method the results of a clinical assessment of the assay performance should be
available. The clinical sensitivity and specificity (i.e. positive and negative predictive values) of the assays
should be quoted.
Quality assurance

Laboratories should run internal quality control at concentrations appropriate for the range of
results obtained. A pool with a calcitonin concentration close to the minimum detectable limit
should also be run to ensure good baseline security (IV, C).
Laboratories should participate in a recognised and accredited external quality assessment scheme
(IV, C).

Appendix 2, Recognition of MEN2B
MEN2B Clinical Features
(Reproduced with the consent of the patients)

Please insert here the *.pdf file: 'MEN2B&W'

Appendix 3. Search methodology

Literature searches were carries out on a number of databases and world-wide web resources. Since
there are few systematic reviews and randomised controlled trials in this area, a search strategy was
designed to retrieve reviews and papers reporting on all primary studies including cohort studies, case
control studies and other clinical trials. No limit was placed on language or age of subjects, and there
were no limits placed on date of publication.
It was also necessary to limit searches to differentiated thyroid cancer, and exclude undifferentiated
anaplastic thyroid cancer. The search therefore included the following items:
Differentiated thyroid cancer Thyroid neoplasm Thyroid nodule Carcinoma- papillary, follicular Hürthle cell Medullary thyroid cancer Multiple endocrine neoplasia type 2 A medline search covered 1966-2006. This was supplemented by searches on the Cochrane Library and a number of world-wide web resources, including: Cancerlit CancerNet National Guideline Clearinghouse National Research Register SIGN Appendix 4. References

1. Guidance on Cancer Services - Improving Outcomes in Head and Neck Cancers – The Manual, 2004.

2. Paediatric Endocrine Tumours. A Multi-Disciplinary Consensus Statement of Best Practice from a Working
Group Convened Under the Auspices of the BSPED and UKCCSG, ed H Spoudeas 2005.
3. US Dept of Health and Human Services. Agency for Health Care Policy and Research. Acute Pain
Management: operative or medical procedures and trauma. Rockville (MD): The Agency: 1992. Clinical Practice
Guideline No. 1 AHCPR Publication No. 92-0023 p.107.
4. Agency for Health Care Policy and Research (AHCPR). Management of cancer pain: adults. Quick reference
guide for clinicians. Rockville (MD): U.S. Department of Health and Human Services, Public Health Service,
AHCPR; 1994 Mar. 29 p. (Clinical practice guideline; no. 9).
5. NHS Manual of Cancer Services Standards, 2000.

6. Teppo L, Hakulinen E and Eurocare Working Group. Variation in survival of adult patients with thyroid cancer
in Europe. Eur J Cancer 1998;34:2238-52.
7. Coleman PM, Babb P, Damiecki P, et al. Cancer survival trends in England and Wales 1971-1995: Deprivation
and NHS region London: Stationery Office, 1999 (Series SMPS No. 61), pp471-8.
8. CancerStats Monograph 2004. Cancer incidence, survival and mortality in the UK and EU, ed Toms JR.
London: Cancer Research UK 2004.
9. Mazzaferri EL. An Overview of the Management of Papillary and Follicular Thyroid Carcinoma. Thyroid
10. , gical tumor-node-metastasis (pTNM) staging for
papillary and follicular thyroid carcinomas: a retrospective analys
11. , et al. Prognostic scoring systems in patients with follicular thyroid cancer: a
comparison of different staging systems in predicting the patient outcome. Thyroid 2004;14:453-8.
12. TNM Klasifikation maligner Tumoren, ed Wittekind Ch, Wagner G. 5th edition, Springer, UICC 1997.
12a. Brierley JD, Panzarella T. A comparison of different staging systems predictability of patient outcome.
Thyroid carcinoma as an example. Cancer 1997;79:2414-23.
12b. Passler C, Prager G, Scheuba C, Kaserer K, Zettinig G, Niederle B. Application of staging systems for
differentiated thyroid carcinoma in an endemic goiter region with iodine substitution. Ann Surg 2003;237:227-34.
12c. Lo CY, Chan WF, Lam KY, Wan KY. Follicular thyroid carcinoma: the role of histology and staging systems
in predicting survival. Ann Surg 2005;242:708-15.
13. Mazzaferri E L, Jhiang S M. Long-term impact of initial surgical and medical therapy on papillary and
follicular thyroid cancer Am J Med 1994;97:418-28.
14. Carcangiu ML, Zampi G, Pupi A, Castagnoli A, Rosai J. Papillary carcinoma of the thyroid. A
clinicopathologic study of 241 cases treated at the University of Florence, Italy. Cancer 1985;55:805-28.
15. Simpson W J, McKinney S E, Carruthers J S, Gospodarowicz M K, Sutcliffe S B, Panzarella T. Papillary and
follicular thyroid cancer: prognostic factors in 1578 patients. Am J Med 1987;83:479–88.
16. Tubiana M, Schlumberger M, Rougier P, et al. Long-term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer 1985;55:794-804. 17. Akslen LA, Haldorsen T, Thoresen SO, Glattre E. Survival and causes of death in thyroid cancer: a population-based study of 2479 cases from Norway. Cancer Res 1991;51:1234-41. 18. Hay I D. Papillary thyroid carcinoma. Endocrinol Metab Clin Nor Am 1990;19:545-76. 19. Furmanchuk AW, Averkin JI, Egloff B, et al. Pathomorphological findings in thyroid cancers of children from the Republic of Belarus: a study of 86 cases occurring between 1986 ('post-Chernobyl') and 1991.Histopathology. 1992;21:401-8. 20. Schlumberger M, De Vathaire F, Travagli JP, et al. Differentiated thyroid carcinoma in childhood: long term follow-up of 72 patients. J Clin Endocrinol Metab 1987;65:1088-94. 21. Cady B, Rossi R. An expanded view of risk group definition in differentiated thyroid carcinoma. Surgery 1988;104:947- 53. 22. Brennan M, Bergstralh E H, Heerden J A, McConahey W M. Follicular thyroid cancer treated at the Mayo Clinic 1946–1970. Initial manifestation, pathologic findings, therapy and outcome. Mayo Clinic Proc 1991;66:11-22. 23. Emerick GT, Duh QY, Siperstein AE et al. Diagnosis, treatment and outcome of follicular thyroid carcinoma. Cancer 1993;72:3287-95. 24. Donohue JH, Goldfien SD, Miller TR, Abele JS, Clark OH. Do the prognoses of papillary and follicular thyroid carcinomas differ? Am J Surg 1984;148:168-73. 25.24.Evans HL. Columnar-cell carcinoma of the thyroid. A report of two cases of an aggressive variant of thyroid carcinoma. Am J Clin Pathol 1986;85:77-80. 26. Herrera MF, Hay ID, Wu PS, et al.Hurthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biologic behavior. World J Surg 1992;16:669-74. 27. Akslen LA, LiVolsi VA. Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma. Cancer 2000;88:1902. 28. Rosai J, Zampi G, Carcangiu ML.Papillary carcinoma of the thyroid. A discussion of its several morphologic expressions, with particular emphasis on the follicular variant. Am J Surg Pathol 1983;7:809-17. 29. Hay ID, Bergstralh, E J, Goellner J R, Bersold J R, Grant CS. Predicting outcome in papillary thyroid carcinoma: Development of reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940–1989. Surgery 1993;114:1050-8. 30. Lang W, Choritz H, Hundeshagen H. Risk factors in follicular thyroid carcinomas. A retrospective follow-up study covering a 14-year period with emphasis on morphological findings. Am J Surg Pathol 198610:246-55. 31. DeGroot LJ, Kaplan EL, Shukla MS, Salti G, Straus FH. Morbidity and mortality in follicular thyroid cancer. J Clin Endocrinol Metab 1995;80:2946-53. 32. Yamashita H, Noguchi S, Murakami N, Kawamoto H, Watanabe S. Extracapsular invasion of lymph node metastasis is an indicator of distant metastasis and poor prognosis in patients with thyroid papillary carcinoma. Cancer 1997;80:2268-72. 33. DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment and course of papillary thyroid cancer. J Clin Endocrinol Metab 1990;71:414-24. 34. Dinneen SF, Valimaki MJ, Bergstralh EJ, Goellner JR, Gorman CA, Hay ID. Distant metastases in papillary thyroid carcinoma: 100 cases observed at one institution during 5 decades. J Clin Endocrinol Metab 1995;80:2041- 5. 35. Hoie J, Stenwig AE, Kullmann G, Lindegaard M. Distant metastases in papillary thyroid cancer. A review of 91 patients. Cancer 1988;61:1-6. 36. Pacini F, Cetani F, Miccoli P et al. Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine. World J Surg 1994;18:600-604. 37. International Atomic Energy Agency (IAEA). Intervention criteria in a nuclear or nuclear radiation emergency. Safety Series 109, IAEA, Vienna, 1991. 38. International Commission on Radiological Protection (ICRP). Principles for intervention for protection of the public in radiological emergency (ICRC Publication 63). Oxford: Pergamon Press, 1991. 39. Giordano TJ, Kuick R, Thomas DG, et al. Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene 2005;24:6646-56. 40. Hancock SL, Cox RS, McDougallI R. Thyroid disease after treatment of Hodgkin's disease. N Engl J Med 1991;325:599-605. 41. Ron E, Lubin J H, Shore R E et al. Thyroid cancer after exposure of external radiation: A pooled analysis of seven studies. Radiat Research 1995;141:259-77. 42. Thompson DE, Mabuchi K, Ron E, et al. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987. Radiat Res 1994;137(2 Suppl):S17-67. 43. Winship T, Rosvoll R V. Thyroid carcinoma in childhood: final report on a 20 year study. Clinical Proc Child Hosp Wash DC 1970;26:327-48. 44. Franceschi S, Boyle P, Maisonneuve P, et al. The epidemiology of thyroid carcinoma. Crit Rev Oncogen 1993;4:25-52. 45. Levi F, Franceschi S, la Vecchia C, et al. Prior thyroid disease and risk of thyroid cancer in Switzerland. Eur J Cancer 1991;27:85-8. 46. Preston-Martin S, Berenstein L, Pike MC, Maldonado AA, Henderson BE. Thyroid cancer among young women related to prior thyroid disease and pregnancy history. Br J Cancer 1987;55:191-5. 47. Mack WJ, Preston-Martin S. Epidemiology of thyroid cancer. In "Thyroid Cancer", ed Fagin JA, Kluwer Academic Publishers, Boston, 1998 pp1-25. 48. Holm LE, Blomgren H, Lowhagen T. Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med 1985;312:601-4. 49. Hegedus L. Clinical practice. The thyroid nodule. N Engl J Med 2004;351:1764-71. 50. Cancer Waiting Times http://www.dh.gov.uk 51. Manual of Cancer Services Standards, 2000. http://www.doh.gov.uk/cancer/mcss.htm). 52. Kumar H, Daykin J, Holder R, et al. Gender, clinical findings and serum thyrotropin measurements in the prediction of thyroid neoplasia in 1005 patients presenting with thyroid enlargement and investigated by fine needle aspiration cytology (FNAC). Thyroid 1999;9:1105-9. 53. Cap J, Ryska A, Rehorkova P, Hovorkova E, Kerekes Z, Pohnetalova D. Sensitivity and specificity of the fine needle aspiration biopsy of the thyroid: clinical point of view. Clin Endocrinol 1999;51:509-15. 54. Danese D, Sciacchitano S, Farsetti A et al. Diagnostic accuracy of conventional versus sonography-guided fine- needle aspiration biopsy of thyroid nodules. Thyroid 1998;8:15-21. 55.UK guidelines for the use of thyroid function tests. The Association of Clinical Biochemsists, 2006. http://www.acb.org.uk/docs/TFTguidelinefinal.pdf#search=%22propylthiouracil%20manufacturer%20uk%22 56. Elisei R, Bottici V, Luchetti F, et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J Clin Endocrinol Metab 2004;89:163-8. 57. Rieu M, Lame MC, Richard A et al. Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules. Clin Endocrinol 1995;42: 453-60. 58. Gittoes NJ, Miller MR, Daykin J, Sheppard MC, Franklyn JA. Upper airways obstruction in 153 consecutive p atients presenting with thyroid enlargement. BMJ. 1996;312:484. 59. Rojeski MT, Gharib H. Nodular thyroid disease: evaluation and management. N Engl J Med 1985;313:428-36. 60. Giuffrida D, Gharib H. Controversies in the management of cold, hot and occult thyroid nodules. Am J Med 1995;99:642-50. 61. Tabaqchali MA, Hanson JM, Johnson SJ, Wadehra V, Lennard TW, Proud G. Thyroid aspiration cytology in Newcastle: a six year cytology/histology correlation study. Ann R Coll Surg Engl. 2000;82:149-55. 62. Sclabas GM, Staerkel GA, Shapiro SE, et al. Fine-needle aspiration of the thyroid and correlation with histopathology in a contemporary series of 240 patients. Am J Surg. 2003;186:702-9. 63. Caron NR, Cord S and Clark OH. The specialist endocrine surgeon. In: "Practical management of thyroid cancer: a multidisciplinary approach", ed Ernest L. Mazzaferri, Clive Harmer, Ujjal K. Mallick, Pat Kendall-Taylor, Springer 2006 pp121-134 64. Mallick UK. Thyroid cancer multidisciplinary team and the organisational paradigm. In: "Practical management of thyroid cancer: a multidisciplinary approach", ed Ernest L. Mazzaferri, Clive Harmer, Ujjal K. Mallick, Pat Kendall-Taylor, Springer 2006 pp39-53. 65. Wells PS, Lensing AW, Hirsh J. Graduated compression stockings in the prevention of postoperative venous thromboembolism. A meta-analysis. Arch Intern Med. 1994;154:67-72. 66. Randolph GW. The importance of preoperastive laryngoscopy in patients undergoing thyroidectomy: voice, vocal cord function, and the preoperative detection of invasive thyroid malignancy. Surgery 2006;139:363-4. 67. Watkinson JC, Franklyn JA, Olliff JF. Detection and surgical treatment of cervical lymph nodes in differentiated thyroid cancer. Thyroid 2006;16:187-94. 68. Schlumberger M J. Papillary and follicular thyroid carcinoma. N Engl J Med 1998;338:297-306. 69. Cooper DS, Doherty GM, Haugen BR, et al. The American Thyroid Association Guidelines Taskforce. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006;16:109 42. 70. Pacini F, Schlumberger M, Dralle H, et al. European Thyroid Cancer Taskforce. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol. 2006;154:787-803. 71. Bi J, Lu B. Advances in diagnosis and management of thyroid neoplasms. Curr Opin Oncol 2000;12:54-9. 72. Hundahl SA, Cady B, Cunningham MP, et al. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the United States during 1996. US and German Thyroid Cancer Study Group. An American College of Surgeons Cancer Patient Care Evaluation Study. Cancer 2000;89:202-17. 73. Van De Velde CJH, Hamming JF, et al. Report of the consensus development conference on the management of differentiated thyroid cancer in the Netherlands. Eur J Cancer Clin Oncol 1988;24:287-92. 74. Falk SA, McCaffrey TV. Management of recurrent laryngeal nerve in suspected and proven thyroid cancer. Otolaryngol Head Neck Surg 1995;113:42-8. 75. Cernea CR., Ferraz AR, Monteiro S etal., Identification of the external branch of the superior laryngeal nerve during thyroidectomy. Am J Surg 1992;164:634-9. 76. Lennquist S, Cahlin C, Smeds S. The superior laryngeal nerve in thyroid surgery. Surgery 1987;102:999-1008. 77. Olson JA Jr, DeBenedetti MK, Baumann DS, Wells SA Jr. Parathyroid autotransplantation during thyroidectomy. Results of long-term follow-up. Ann Surg 1996; 223: 472−80. 78. Cheah WK, Arici C, Ituarte PH, Siperstein AE, Duh QY, Clark OH. Complications of neck dissection for thyroid cancer. World J Surg 2002;26:1013-6. 79. van Santen HM, Aronson DC, Vulsma T, et al. Frequent adverse events after treatment for childhood-onset differentiated thyroid carcinoma: a single institute experience. Eur J Cancer 2004;40:1743-51. 80. Dralle H Dralle H, Damm I, et al. Compartment orientated microdissection of regional nodes in medullary thyroid carcinoma. Surgery Today 1994;24:112-21. 81. Mulcahy MM, Cohen JI, Anderson PE, et al. Relative accuracy of fine-needle aspiration and frozen section in the diagnosis pf ell-differentiated thyroid cancer. Laryngoscope 1998;104:494-6. 82. van Heerden JA, Hay ID, Goellner RJ et al. Follicular thyroid carcinoma with capsular invasion alone: a non threatening malignancy. Surgery 1992;112:1130-6. 83. Pacini F, Schlumberger M, Harmer C, et al. Post-surgical use of radioiodine (131I) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation: a consensus report. Eur J Endocrinol 2005;153:651-9. 84. Sobrinho-Simoes M, Maximo V, Castro IV, et al. Hurthle (oncocytic) cell tumors of thyroid: etiopathogenesis, diagnosis and clinical significance. Int J Surg Pathol. 2005;13:29-35. 85. Pearce EN, Braverman LE. Papillary thyroid microcarcinoma outcomes and implications for treatment. J Clin Endocrinol Metab 2004;89:3710-2. 86. Drucker WD, Robbins RJ. Papillary microcarcinoma. In: Practical management of thyroid cancer: A multidisciplinary approach. EL Mazzaferri, C Harmer, UK Mallick, P Kendall-Taylor (eds). Springer-Verlag, London, 2006, pp371-389. 87. Mazzaferri EL. An overview of the management of thyroid cancer. In: "Practical management of thyroid cancer: a multidisciplinary approach", ed Ernest L. Mazzaferri, Clive Harmer, Ujjal K. Mallick, Pat Kendall- Taylor, Springer 2006 pp1-28. 88. Feldt-Rasmussen U, Petersen PH, Date J, Madsen CM. Serum thyroglobulin in patients undergoing subtotal thyroidectomy for toxic and nontoxic goiter. J Endocrinol Invest 1982;5:161-4. 89. Izumi M, Kubo I, Taura M, et al. Kinetic study of immunoreactive human thyroglobulin. J Clin Endocrinol Metab. 1986;62:410-2. 90. Ozata M, Suzuki S, Miyamoto T, Liu RT, Fierro-Renoy F, DeGroot LJ 1994 Serum thyroglobulin in the follow-up of patients with treated differentiated thyroid cancer. J Clin Endocrinol Metab 79:98–105 91. Hocevar M, Auersperg M, Stanovnik L. The dynamics of serum thyroglobulin elimination from the body after thyroid surgery. Eur J Surg Oncol. 1997;23:208-10. 92. Cha C, Chen H, Westra WH, Udelsman R. Primary thyroid lymphoma: can the diagnosis be made solely by fine-needle aspiration? Ann Surg Oncol. 2002;9:298-302. 93. Harrington KJ, Michalaki VJ, Vini L, et al. Management of non-Hodgkin's lymphoma of the thyroid: the Royal Marsden Hospital experience. Br J Radiol. 2005;78:405-10. 94. Giuffrida D, Gharib H. Anaplastic thyroid carcinoma: current diagnosis and treatment Ann Oncol 2000;11:1083-9. 95. Haigh PI, Ituarte PH, Wu HS, et al. Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival. Cancer 2001;91:2335-42. 96. Haq M, Harmer C. Non-surgical management of thyroid cancer. In: "Practical management of thyroid cancer: a multidisciplinary approach", ed Ernest L. Mazzaferri, Clive Harmer, Ujjal K. Mallick, Pat Kendall-Taylor, Springer 2006 pp171-191. 97. Pluijmen MJ, Eustatia-Rutten C, Goslings BM, et al. Effects of low-iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma. Clin Endocrinol 2003;58:428-35. 98. Lakshmanan M, Schaffer A, Robbins J, Reynolds J, Norton J. A simplified low iodine diet in I131 scanning and therapy of thyroid cancer. Clin Nucl Med 1988;13:866-8. 99. Maxon H R. Quantitative radioiodine therapy in the treatment of differentiated thyroid cancer. Q J Nucl Med 1999;43:313-23. 100. Maxon HR, Smith HS. Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. Endo Metab Clin Nor Am 1990:19:685–718. 101. Leger F A, Izembart M, Dagousset F, et al. Decreased uptake of therapeutic doses of iodine 131 after 185 MBq iodine 131 diagnostic imaging for thyroid remnants in differentiated thyroid carcinoma. Euro J Nuc Med 1998;25;242–6. 102. Park HM, Park YA, Jhow XH. Detection of thyroid remnant/metastases with stunning – an ongoing dilemma. Thyroid 1997;7:277–80. 103. Bal CS, Kumar A, Pant GS. Radioiodine dose for remnant ablation in differentiated thyroid carcinoma: a randomized clinical trial in 509 patients. J Clin Endocrinol Metab 2004;89:1666-73. 104. Vini L, Harmer C. Radioiodine treatment for differentiated thyroid cancer. J Clin Oncol 2000;12:365-72. 105. Hyer S, Vini L, O'Connell M, Pratt B, Harmer C. Testicular dose and fertility in men following I(131) therapy for thyroid cancer. Clin Endocrinol (Oxf). 2002;56:755-8. 106. Clinical Practice Guidelines for the Management of Thyroid Carcinoma. American Association of Clinical Endocrinologists, 2001. 107. Tsang RW, Brierley JD, Simpson WJ, Panzarella T, Gospodarowiczz MK, Sutcliffe SB. The effects of surgery, radioiodine and external radiation therapy n the clinical outcome of patients with differentiated thyroid carcinoma. Cancer 1998;82:375-88. 108. Brierley J, Tsang R, Panzarella T, Bana N. Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years. Clin Endocrinol 2005;63:418-27. 109. Sawka AM, Thephamongkhol K, Brouwers M, Thabane L, Browman G, Gerstein HC. Clinical review 170: A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well differentiated thyroid cancer. J Clin Endocrinol Metab 2004;89:3668-76. 110. Hay ID, McConahey WM, Goellner JR. Managing patients with papillary thyroid carcinoma: insights gained from the Mayo Clinic's experience of treating 2,512 consecutive patients during 1940 through 2000. Trans Am Clin Climatol Assoc 2002;113:241-60. 111. Rubino C, de Vathaire F, Dottorini ME, et al. Second primary malignancies in thyroid cancer patients. Br J Cancer 2003;89:1638-44. 112. Sandeep TC, Strachan MW, Reynolds RM, et al. Second primary cancers in thyroid cancer patients: a multinational record linkage study. J Clin Endocrinol Metab 2006;91:1819-25. 113. Reiners C, Farahati J. I131 therapy of thyroid cancer patient. Q J Nuc. Med 1999;43:324-35. 114. Ringel MD, Ladenson PW. Controversies in the follow-up and management of well-differentiated thyroid cancer. Endocr Relat Cancer 2004;11:97-116. 115. Bal C, Padhy AK, Jana S, Pant GS, Basu AK. Prospective randomized clinical trial to evaluate the optimal dose of 131 I for remnant ablation in patients with differentiated thyroid carcinoma. Cancer 1996;77:2574-80. 116. Sirisalipoch S, Buachum V, Pasawang P, Tepmongkol S. Prospective randomized trial for the evaluation of the efficacy of low vs high dose 131I for post-operative remnant ablation in differentiated thyroid cancer. World J Nuc Med 2004;3(Suppl 1):S36. 117. Haq MS, McCready RV, Harmer CL. Treatment of advanced differentiated thyroid carcinoma with high activity radioiodine therapy. Nucl Med Commun. 2004;25:799-805. 118. Pacini F, Ladenson PW, Schlumberger M, et al. Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. J Clin Endocrinol Metab 2006;91:926-32. 119. Fatourechi V, Hay ID, Mullan BP, et al. Are posttherapy radioiodine scans informative and do they influence subsequent therapy of patients with differentiated thyroid cancer? Thyroid 2000;10:573-7. 120. Roos DE. Ransomised trials on radiactive iodine ablation of thyroid remnants for thyroid carcinoma – a critique. Int J. Radiation Oncology Biol. Phys 1999;44:493–5. 121. Cailleux AF, Baudin E, Travagli J P, Ricard M, Schlumberger M. Is Diagnostic I131 scanning useful after total thyroid ablation for differentiated thyroid cancer. J Clin Endocrinol Metab 2000;85:175-8. 122. Schlumberger M, Berg G, Cohen O, et al. Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J Endocrinol 2004;150:105-12. 123. Haugen B R, Pacini F, Reiners C et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 1999;84:3877-55. 124. Mazzaferri EL, Robbins RJ, Spencer CA, et al. A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 2003;88:1433 41. 125. Notes for guidance on clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Administration of Radioactive Substances Advisory Committee, 2006. http://www.arsac.org.uk/notes_for_guidence/docs/arsac_nfg.pdf 126. Schlumberger M, De Vathaire F, Ceccarelli C, et al. Exposure to radioiodine (I131) for scintigraphy or therapy does not preclude pregnancy in thyroid cancer patients. J Nucl Med 1996;37:606-12. 127. Ayala C, Navarro E, Rodriguez J R, Silva H, Venegas E, Astorga R. Conception after I131 therapy for differentiated thyroid cancer. Thyroid 1998;8:1009-11. 128. Dottorini ME, Lomuscio G, Mazzucchelli L, Vignati A, Colombo L. Assessment of female fertility and carcinogenesis after iodine I131 therapy for differentiated thyroid carcinoma. J Nuc Med 1995;36:21–7. 129. Bal C, Kumar A, Tripathi M, et al. High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring. Int J Radiat Oncol Biol Phys. 2005;63:449-55. 130. Schroeder PR, Haugen BR, Pacini F, et al. A Comparison of Short-term Changes in Health-related Quality of Life in Thyroid Carcinoma Patients Undergoing Diagnostic Evaluation with rhTSH Compared to Thyroid Hormone Withdrawal. J Clin Endocrinol Metab 2006;91:878-84. 131. Schlumberger M, Pacini F. Hazards of medical use of iodine 131, in 'Thyroid Tumours' Nucleon, Paris. 1997;223-235. 132. Simpson WJ, Panzarella T, Carruthers JS, et al. Papillary and Follicular Thyroid Cancer. Impact of treatment in 1578 patients. Int J Radiat Oncol Biol Phys 1988;14:1063-75. 133. de Vathaire F, Schlumberger M, Delisle MJ, et al. Leukaemia and cancers following iodine 131 administration for thyroid cancer. Br J Cancer 1997;75:734-9. 134. Dulgeroff J A, Hershman J M. Medical therapy for differentiated thyroid carcinoma. Endocr Rev 1994;15:500–5. 135. Edmonds C J, Smith T. The long term hazards of treatment of thyroid cancer with radioiodine. Brit J Radiol 1986;59:45–51. 136. Brown AP, Greening WP, McCready VR, et al. Radioiodine treatment of metastatic thyroid cancer. Royal Marsden Experience. 1984;5:324–27. 137. Maheshwari YK, Hill CS jnr, Haynie GP, et al. I131 therapy in differentiated thyroid carcinoma: MD Anderson Hospital Experience. Cancer 1981;47:664-71. 138. Rall JE, Alpers JB, Lewallen CG, Sonenberg M, Berman M, Rawson RW. Radiation pneumonitis and fibrosis: a complication of radioiodine treatment of pulmonary metastases from cancer of the thyroid. J Clin Endocinol Metab 1957;17:1263-76. 139. Meadows KM, Amdur RJ, Morris CG, Villaret DB, Mazzaferri EL, Mendenhall WM. External beam radiotherapy for differentiated thyroid cancer. Am J Otolaryngol 2006;27:24-8. 140. Biermann M, Pixberg M, Schuck A, Willich N, Heinecke A, Schober O. (2005) External beam radiotherapy. In: Biersack H-J, Grünwald F (eds.). Thyroid cancer. Heidelberg: Springer, 139-161. 141. Tubiana M, Hadad E, Schlumberger M, et al, External Radiotherapy in Thyroid Cancers. Cancer 1985;55 (suppl):206 – 271. 142. Harmer CL, McCready VR. Thyroid cancer: differentiated carcinoma. Cancer Treat Rev 1996;22:161-77. 143. Taylor T, Specker B, Robbins J, et al. Outcome after treatment of high risk papillary and non-Hurthle-cell follicular thyroid carcinoma. Ann Intern Med 1998;129:622-7. 144. Harmer C, Bidmead M, Shepherd S, et al. Radiotherapy planning techniques for thyroid cancer. Br J Radiol 1998;71;1069-75 145. Samaan NA, Schultz PN, Hickey RC, et al. The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients. J Clin Endocrinol Metab 1992;75:714-20. 146. Hall EJ.latrogenic cancer: the impact of intensity-modulated radiotherapy. Clin Oncol 2006;18:277-82. 147. Szubin L, Kacker A, Kakani R, Komisar A, Blaugrund S. The management of post-thyroidectomy hypocalcemia. Ear Nose Throat J. 1996 Sep;75(9):612-4, 616. 148. Bentrem DJ, Rademaker A, Angelos P. Evaluation of serum calcium levels in predicting hypoparathyroidism after total/near-total thyroidectomy or parathyroidectomy. Am Surg. 2001 Mar;67(3):249-51. 149. Chia SH, Weisman RA, Tieu D, Kelly C, Dillmann WH, Orloff LA. Prospective study of perioperative factors predicting hypocalcemia after thyroid and parathyroid surgery. Arch Otolaryngol Head Neck Surg 2006;132:41-45. 150. 128.Thakker RV (2003). Hypocalcemia: Pathogenesis, Differential Diagnosis, and Management. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolisim. 5th Edition. Ed: M J Favus. Pubs: American Society of Bone and Mineral Research, Washington, DC, USA. pp271-274. 151. Biondi B, Filetti S, M Schlumberger. Thyroid-hormone therapy and thyroid cancer: a reassessment. Nature Clin Prac Endocrinol Metab 2005;1:P32-40. 152. Wang PW, Wang ST, Liu RT, et al. Levothyroxine suppression of thyroglobulin in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 1999;84:4549-553. 153. Kamel N, Gullu S, Dagci IS, et al. Degree of thyrotropin suppression in differentiated thyroid cancer without recurrence or metastases. Thyroid 1999;9:1245-8. 154. Pujol P, Daures JP, Nsakala N, et al. Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer. J Clin Endocrinol Metab 1996;81:4318-23. 155. Cooper DS, Specker B, Ho M, et al. Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry. Thyroid 1998;8:737-44. 156. Demers LM, Spencer CA (Eds) Laboratory support for the diagnosis and monitoring of thyroid disease (National Academy of Clinical Biochemistry). http://www.aacc.org/NR/rdonlyres/F343F1C7-8DFB-4718-A912- 030550E087A3/0/3e_thyroid.pdf 157. Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS. Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab 2005;90:5566-75. 158. Feldt-Rasmussen U, Petersen PH, Date J, Madsen CM. Serum thyroglobulin in patients undergoing subtotal thyroidectomy for toxic and nontoxic goiter. J Endocrinol Invest. 1982;5:161-4. 159. Izumi M, Kubo I, Taura M, et al. Kinetic study of immunoreactive human thyroglobulin. J Clin Endocrinol Metab 1986;62:410-2. 160. Hocevar M, Auersperg M, Stanovnik L. The dynamics of serum thyroglobulin elimination from the body after thyroid surgery. Eur J Surg Oncol. 1997;23:208-10. 161. Ozata M, Suzuki S, Miyamoto T, Liu RT, Fierro-Renoy F, DeGroot LJ. Serum thyroglobulin in the follow-up of patients with treated differentiated thyroid cancer. J Clin Endocrinol Metab 1994;79:98-105. 162. Kloos RT, Mazzaferri EL. A single recombinant human thyrotropin-stimulated serum thyroglobulin measurement predicts differentiated thyroid carcinoma metastases three to five years later. J Clin Endocrinol Metab 2005;90:5047-57. 163. Luster M, Lippi F, Jarzab B, Perros P, Lassmann M, Reiners C, Pacini F. rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review. Endocr Relat Cancer 2005;12:49-64. 164. Pacini F, Molinaro E, Castagna MG, et al. Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab 2003;88:3668-73. 165. Kebebew E, Clark OH. Differentiated thyroid cancer ‘complete' rational approach. World J Surg 2000;24:942–51. 166. Wilson PC, Millar BM, Brierley JD. The management of advanced thyroid cancer. Clin Oncol 2004;16:561-8. 167. Van Nostrand D, Atkins F, Yeganeh F, Acio E, Bursaw R, Wartofsky L. Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. Thyroid 2002;12:121-34. 168. Sisson JC. Practical dosimetry of I131 in patients with thyroid carcinoma. Cancer Biother Radiopharm 2002;17:101-5. 169. McDougall, I. Ross. Management of thyroid cancer and related nodular disease. Chapter 6. Springer, 2006. 170. McDougall IR. Management of thyroglobulin positive/whole-body scan negative: is Tg positive/131I therapy useful? J Endocrinol Invest. 2001;24:194-8. 171. Ward G, Hickman PE. Phantoms in the assay tube. J Clin Endocrinol Metab 2004;89:433. 172. Ma C, Xie J, Kuang A. Is empiric 1313I therapy justified for patients with positive Tg and negative 131I whole body scanning results? J Nuclear Med 2005;46:1164-70. 173. van Tol KM, Jager PL, de Vries EG, et al. Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin. Eur J Endocrinol. 2003;148:589- 96. 174. Wang W, Larson SM, Fazzari M, et al. Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinl Metab 2000;85:1107-13. 175. van Tol KM, Jager PL, Piers DA et al. Better yield of 18-flurodexoxyglucose positron emission tomography in patients with metastatic differentiated thyroid cancer during thyrotropin stimulation. Thyroid 2002;12:381-7. 176. Wong, CO, Dworkin AJ. Role of FDG PET in Metastatic Thyroid Cancer. J Nucl Medi 1999;40: 993-4. 177. Chung J K, So Y, Lee J S et al. Value of FDG PET in papillary thyroid carcinoma with negative I131 whole body scan. J Nuc Med 1999;40:986-92. 178. Schluter B, Bohuslaviski KH, Beyer W et al. Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan. J Nucl Medi 2001;42:71–78. 179. Petrich T, Borner AR, Otto D et al. Influence of rhTSH on 18- flurodexoyglucose uptake by differentiated thyroid cancer, J Nucl Med Mol Imaging 2002;29:641-7. 180. Stokkel MP, Reigman HI, Verkooijen RB, Smit JW. Indium-111-Octreotide scintigraphy in differentiated thyroid carcinoma metastases that do not respond to treatment with high-dose I-131. J Cancer Res Clin Oncol 2003;129:287-94. 181. Teunissen JJ, Kwekkeboom DJ, Kooij PP et al, Peptide receptor radionuclide therapy for non radioiodine avid differentiated thyroid cancer, J Nuclear Med 2005;46:107-14. 182. Mazzaferri EL Management of differentiated thyroid carcinoma in patients with negative whole-body radioiodine scans and elevated serum thyroglobulin levels. In: "Practical management of thyroid cancer: a multidisciplinary approach", ed Ernest L. Mazzaferri, Clive Harmer, Ujjal K. Mallick, Pat Kendall-Taylor, Springer 2006 pp237-254. 183. Schlumberger MJ, Mancusi F, Baudin E, Pacini F. I131 therapy for elevated thyroglobulin levels. Thyroid 1997;7:273–5. 184. Carlisle MR, Lu C, McDougall IR. The interpretation of 131I scans in the evaluation of thyroid cancer, with an emphasis on false positive findings. Nucl Med Commun. 2003;24:715-35. 185. Comisky M. Specialist palliative care for anaplastic trhyroid carcinoma. In: "Practical management of thyroid cancer: a multidisciplinary approach", ed Ernest L. Mazzaferri, Clive Harmer, Ujjal K. Mallick, Pat Kendall- Taylor, Springer 2006 pp411-419. 186. Shimaoka K, Schoenfeld DA, Dewys WD, Creech RH, De Conti R. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid cancer. Cancer 1985;56:2155-60. 187. Williams SD, Birch R, Einhorn LH. Phase II evaluation of Doxorubicin plus Cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group Tiral. Cancer Treat Rep 1986;70:405-7. 188. Hoskin P J, Harmer C L, Chemotherapy for thyroid cancer. Radiother Oncol 1987;10:187-94. 189. Saller B. Treatement with Cytotoxic Drugs. Chapter 10. Thyroid Cancer. Biersack AJ and Grunwald F Editors. Second Edition. 2001, Springer. 190. Moosa M & Mazzaferri EL. Outcome of differentiated thyroid cancer diagnosed in pregnant women. J Clin Endocrinol Metab 1997;82:2862-6. 191. Casara D, Rubello D, Saladini G, Piotto G et al. Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations. Eur J Nucl Med 1993;20:192-4. 192. Mandel SJ, Larsen PR, Seely EW, Brent GA. Increased need for thyroxine during pregnancy in women with primary hypothyroidism. N Engl J Med 1990;323:91-6. 193. Schlumberger M, De Vathaire F, Travagli JP, et al. Differentiated thyroid carcinoma in childhood: long term follow-up of 72 patients. Clin Endocrinol Metab 1987:65:1088-94. 194. Zimmerman D, Hay ID, Gough IR, et al. Papillary thyroid carcinoma in children and adults: long-term follow-up of 1039 patients conservatively treated at one institution during three decades. Surgery 1988;104:1157-66. 195. Thompson GB, Hay ID. Current strategies for surgical management and adjuvant treatment of childhood papillary thyroid carcinoma. World J Surg 2004;28:1187-98. 196. La Quaglia MP, Black T, Holcomb GW, et al. Differentiated thyroid cancer: clinical characteristics, treatment, and outcome in patients under 21 years of age who present with distant metastases. A report from the Surgical Discipline Committee of the Children's Cancer Group. J Pediatr Surg 2000;35:955-9. 197. Jarzab B, Handkiewicz Junak D, et al. Multivariate analysis of prognostic factors for differentiated thyroid carcinoma in children. Eur J Nucl Med 2000;27:833-41. 198. Laundau D, Vini L, Hern R A, Harmer C. Thyroid cancer in children: The Royal Marsden Hospital experience. Eur Journal of Cancer 2000;36;214-20. 199. Chen H, Nicol TL, Udelsman R. Follicular lesions of the thyroid. Does frozen section evaluation alter operative management? Ann Surg 1995;222:101-6. 200. Udelsman R, Westra WH, Donovan PI, Sohn TA, Cameron JL. Randomized prospective evaluation of frozen-section analysis for follicular neoplasms of the thyroid. Ann Surg. 2001;233:716-22. 201. Franssila KO, Ackerman LV, Brown CL, Hedinger CE. Follicular carcinoma. Semin Diagn Pathol 1985;2:101-22. 202. Hermanek P, Sobin LH, editors. TNM classification of malignant tumors. 5th ed. New York: Wiley-Liss; 1992. 203. Sherman SI. Toward a standard clinicopathologic staging approach for differentiated thyroid carcinoma. Semin Surg Oncol 1999;16:12-5. 204. Cancer AJCo. AJCC cancer staging manual. 5th ed. Philadelphia: Lippincott-Raven; 1997. 205. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987;102:1088-95. 206. Ogilvie JB, Kebebew E. Indication and timing of thyroid surgery for patients with hereditary medullary thyroid cancer syndromes. J Natl Compr Canc Netw. 2006;4:139-47. 207. Traugott A, Moley JF. Medullary thyroid cancer: medical management and follow-up. Curr Treat Options Oncol. 2005;6:339-46. 208. Gagel RF, Cote GJ, Martins Bughalo MJG, et al. Clinical use of molecular information in the management of multiple endocrine neoplasia type A. J Intern Med 1995;238:333-41. 209. Carlson KM, Bracamontes J, Jackson CE, et al. Parent of origin effects in multiple endocrine neoplasia type 2B. Am J Hum Genet 1994;55:1076-8. 210. Marsh DJ, McDowall D, Hyland VJ, et al. The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families. Clin Endocrinol 1996;44:213-20. 211. Wells SA, Dilley WG, Farndon JR, et al. Early diagnosis and treatment of medullary thyroid carcinoma. Arch Intern Med 1985;145:1248-52. 212. Raue E, Kraimps JL, Dralle H, et al. Primary hyperparathyroidism in multiple endocrine neoplasia type 2A. J Intern Med 1995;238:369-73. 213. Demers, L, Spencer CA. National Academy of Clinical Biochemists: Laboratory support for the diagnosis and monitoring of thyroid disease, 2003. 214. Frilling A, Dralle H, Eng C, et al. Presymptomatic DNA screening in families with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. Surgery 1995;118:1099-104. 215.O'Riordain DS, O'Brien T, Hay ID, et al. Medullary thyroid carcinoma in multiple endocrine neoplasia type 2A and 2B. Surgery 1994;116:1017-23. 216. Pacini F, Romei C, Miccoli P, et al. Early treatment of hereditary medullary thyroid carcinoma after attribution of multiple endocrine neoplasia type 2 gene carrier status by screening for ret gene mutations. Surgery 1995;118:1031-5. 217. Wells SA, Chi DD, Toshima K, et al. Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2. Ann Surg 1994;220:237-50. 218. Ukkat J, Gimm O, Brauckhoff M, Bilkenroth U, Dralle H. Single center experience in primary surgery for medullary thyroid carcinoma. World J Surg 2004;28:1271-4. 219. Machens A, Holzhausen HJ, Thanh PN, Dralle H. Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutations. Surgery 2003;134:425-31. 220. van Heurn LW, Schaap C, Sie G, et al. Predictive DNA testing for multiple endocrine neoplasia 2: a therapeutic challenge of prophylactic thyroidectomy in very young children. J Pediatr Surg. 1999;34:568-71. 221. de Groot JW, Links TP, Plukker JT, Lips CJ, Hofstra RM. RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors. Endocr Rev. 2006;27:535-60. 222. Machens A, Ukkat J, Brauckhoff M, Gimm O, Dralle H. Advances in the management of hereditary medullary thyroid cancer. J Intern Med 2005;257:50-9. 223. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;86:5658-71. 224. Fugazzola L, Pinchera A, Luchetti F, et al. Disappearance rate of serum calcitonin after total thyroidectomy for medullary thyroid carcinoma. Int J Biol Markers 1994;9:21-4. 225. Dralle H. Lymph node dissection and medullary thyroid carcinoma. Br J Surg. 2002;89:1073-5. 226. Modigliani E, Franc B, Niccoli-Sire P. Diagnosis and treatment of medullary thyroid cancer. Baillieres Best Pract Res Clin Endocrinol Metab 2000;14:631-49. 227. Tung WS, Vesely TM, Moley JF. Laparoscopic detection of hepatic metastases in patients with residual or recurrent medullary thyroid cancer. Surgery 1995;118:1024-9. 228. Szavcsur P, Godeny M, Bajzik G, et al. Angiography-proven liver metastases explain low efficacy of lymph node dissections in medullary thyroid cancer patients. Eur J Surg Oncol 2005;31:183-90. 229. Fife KM, Bower M, Harmer C. Medullary thyroid cancer: the role of radiotherapy in local control. Eur J Surg Oncol 1996;22:588-91. 230. Hyer SL, Vini L, A'Hern R, Harmer C. Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival. Eur J Surg Oncol 2000;26:686-90. 230. Pinchera A, Elisei R. Medullary thyroid caner: diagnosis and management. In: "Practical management of thyroid cancer: a multidisciplinary approach", ed Ernest L. Mazzaferri, Clive Harmer, Ujjal K. Mallick, Pat Kendall-Taylor, Springer 2006 pp255-280. 231. Orlandi F, Caraci P, Berruti A, et al. Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol 1994;5:763-5. 232. Schlumberger M, Abdelmoumene N, Delisle MJ, Couette JE. Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. The Groupe d'Etude des Tumeurs a Calcitonine (GETC). Br J Cancer 1995;71:363-5. 233. Clarke SE, Lazarus CR, Edwards S, et al. Scintigraphy and treatment of medullary carcinoma of the thyroid with iodine-131 metaiodobenzylguanidine. J Nucl Med 1987 ;28:1820-5. 234. Clarke SE. [131I]metaiodobenzylguanidine therapy in medullary thyroid cancer: Guy's Hospital experience. J Nucl Biol Med 1991;35:323-6. 235. Kaltsas G, Rockall A, Papadogias D, Reznek R, Grossman AB. Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumours. Eur J Endocrinol 2004;151:15-27. 236. Schott M, Seissler J Lettmann M et al. Immunotherapy for meduallry thyroid carcinoma by dendritic cell vaccination. J Clin Endo Metabolism 2001;86:4965-69. 237. Sala E, Mologni L, Cazzaniga S, Papinutto E, Gambacorti-Passerini C. A rapid method for the purification of wild-type and V804M mutant ret catalytic domain: A tool to study thyroid cancer. Int J Biol Macromol 2006;39:60- 5. 238. Bolino A, Schuffenecker I, Luo Y, et al. RET mutations in exons 13 and 14 of FMTC patients. Oncogene 1995;10:2415-9. 239. Borrello MG, Smith DP, Pasini B, et al. RET activation by germline MEN-2A and MEN-2B mutations. Oncogene 1995;11:2419-27. 240. Eng C, Clayton D, Schuffenecker I et al. The relationship between specific ret protooncogene mutations and disease phenotype in multiple endocrine neoplasia type 2: International RET Mutation Consortium. JAMA 1996;276:1575. 241. Eng C, Mulligan LM, Smith DP, et al. Mutation of the RET protooncogene in sporadic medullary thyroid carcinoma. Genes Chromosomes Cancer 1995;12:209-12. 242. Lips CJM, Landsvater RM, Hoppener JWM, et al. Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 1994;331:828. 243. Mulligan LM, Eng C, Attie T, et al. Diverse phenotypes associated with exon 10 mutations of the RET protooncogene. Hum Mol Genet 1994;3:2163-7. 244. Mulligan LM, Eng C, Healey CS, et al. Specific mutations of the RET protooncogene are related to disease phenotype in MEN 2A and FMTC. Nature Genet 1994;6:70. 245. Mulligan LM, Gardner E, Smith BA, et al. Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2. Genes Chromosomes Cancer 1993;6:166-77. 246. Mulligan LM, Kwok JBJ, Healey CS, et al. Germline mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993;363:458-60. 247. Mulligan LM, Marsh DJ, Robinson BG, et al. Genotype-phenotype correlation in MEN 2; report of the international RET mutations consortium. J Intern Med 1995;238:343-6. 248. Farndon JR, Leight GS, Dilley WG, et al. Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity. Br J Surg 1986;73:278-81. 249. Russell CF, Van Heerden JA, Sizemore GW, et al. The surgical management of medullary thyroid carcinoma. Ann Surg 1983;197:42-48. 250. O'Riordain DS, O'Brien T, Crotty TB, et al. Multiple endocrine neoplasia type 2B: more than an endocrine disorder. Surgery 1995;118:936-42. 251. Samaan NA, Draznin MB, Halpin RE, et al. Multiple endocrine syndrome type IIB in early childhood. Cancer 1991;68:1832-4. 252. Carlson KM, Dou S, Chi D, et al. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci USA 1994;91:1579-83. 253. Toogood AA, Eng C, Smith DP, et al. No mutation at codon 918 of the RET gene in a family with multiple endocrine neoplasia type 2B. Clin Endocrinol 1995;43:759-62. 254. International Atomic Energy Agency (IAEA). International criteria in a nuclear or nuclear radiation emergency. Safety Series 109, Vienna: IAEA, 1991. 255. International Commision on Radiological Protection (ICRP). Princliples for intervention for protection of the public in a radiological emergency. ICRC Publication 63. Oxford: Pergamon Press, 1991. 256. Spencer CA. Challenges of serum thyroglobulin (Tg) measurement in the presence of Tg autoantibodies. J Clin Endocrinol Metab 2004;89:3702-4. 257. Stockigt JR. Ambiguous thyroglobulin assay results in the follow-up of differentiated thyroid carcinoma. J Clin Endocrinol Metab 2005;90:5904-5. 257. Weightman DR, Mallick UK, Fenwick JD, Perros P. Discordant serum thyroglobulin results generated by two classes of assay in patients with thyroid carcinoma: correlation with clinical outcome after 3 years of follow-up. Cancer 2003;98:41-7.
Appendix 5. Patient information
Patient representatives have been fully involved in each stage of development of the guidelines and the patient
information literature.


Patient support groups
British Thyroid Foundation
Rivington Street Butterfly North East
Association for Multiple Endocrine Neoplasia Disorde
31 Pennington Place Tel: 01207 545469 email: [email protected] Web sites with useful information for patients

British Thyroid Foundation

(information re MEN syndromes)

http://www.cancerbacup.org.uk/ cancerBacup

Butterfly Northeast

Thyroid Foundation of America


Endocrine Society information for patients

Medline (search the medical literature)

Medline (information for patients)

Thyroid Cancer Survivors' Association

Patient Information Leaflet 1
The Thyroid Gland And Thyroid Cancer

Your Tests and Treatment
The thyroid gland
What is the thyroid gland?

The thyroid gland is an endocrine gland; this means that it makes hormones which are released into the
bloodstream. Hormones act as messengers to affect cells and tissues in other parts of the body.
Where is the thyroid gland?

The thyroid gland is made up of two lobes (each about the size of half a plum) which are joined together
by a ridge of thyroid tissue called the isthmus. The two lobes lie on either side of your windpipe, with the
gland as a whole lying just below your Adam's Apple.

What does the thyroid gland do?

• The thyroid gland produces three hormones which it secretes into the bloodstream. The first is called
‘Thyroxine' which contains four atoms of iodine and is often called T4. If little or no thyroxine is produced it can easily be replaced with medication. • The second is called ‘Triiodothyronine' which contains three atoms of iodine and is often called T3. In the cells and tissues of the body the T4 is converted into T3, and it is the T3 (derived from T4, or secreted as T3 from the thyroid gland) that is active and influences the activity of all the cells and tissues of the body. If little or no T3 is produced it can easily be replaced with medication. • The third is called ‘Calcitonin' which is produced in response to increased levels of calcium in the blood. Calcitonin helps to lower calcium and phosphate levels in the blood by promoting their excretion. This hormone is produced in excess when medullary thyroid cancer is present. If little or no calcitonin is produced the body can function perfectly well without it having to be replaced.

What do the thyroid hormones do?

Thyroid hormones affect the metabolism of your body cells; that is, they regulate the speed at which your
body cells work. If too much of the thyroid hormones are secreted, the body cells work faster than
normal, and you have ‘hyperthyroidism'. However if too little of the thyroid hormones are secreted then
the body cells work slower than normal, and you have ‘hypothyroidism'.

How is the thyroid gland controlled?

Most glands work in conjunction with other glands, and the thyroid gland works with the pituitary gland.
The thyroid is controlled by the pituitary, which lies underneath your brain in your skull and senses the
levels of thyroid hormones in your bloodstream. If the levels drop below normal, the pituitary reacts by
secreting a hormone called the ‘thyroid stimulating hormone' which is often called TSH. TSH stimulates
the thyroid gland to secrete more T3 and T4. Should the thyroid hormone levels rise above normal levels
the pituitary senses this and stops secreting TSH and so the thyroid gland slows down its secretion of T3
and T4. If you need thyroxine medication this does not cause any problems to TSH.

How is thyroid activity measured?

Your doctor will be able to get a good assessment of your thyroid gland activity by taking a history of your
symptoms and by a physical examination. However, to gain an exact level of the thyroid hormones, it is
necessary to take a small sample of blood, which when analysed in the laboratory will show how much T4 and
T3 is being secreted, and how active your pituitary is, by measuring the level of TSH. These tests are sometimes
called thyroid function tests or TFTs.
What are the parathyroid glands and how do they affect calcium levels?

Another set of glands, that lie next to the thyroid gland, are the parathyroid glands. There are normally
four parathyroids, although this can sometimes vary. The parathyroids produce Parathyroid Hormone
(PTH) and this regulates the concentration of calcium in the blood. Normal calcium levels in the blood
are essential for healthy bones, blood clotting, cardiac rhythm and function of the cells, as well as for
general well-being.
Thyroid cancer
Most cancers of the thyroid gland are very slow growing and it may be many years before the symptoms present
Are all thyroid cancer the same?

No, there are different types:-
Papillary cell carcinoma - This is the most common thyroid cancer. It is more common in younger
people, particularly women. • Follicular cell carcinoma - This is less common, and tends to occur in slightly older people than those
with papillary cancer. • Medullary cell carcinoma -This is a rare cancer, which is sometimes hereditary. Ask your specialist
about genetic counselling and he/she will arrange it.
Most thyroid cancers are very treatable and curable, but there is the possibility of recurrence, specially in the
very young and very old. This can occur at any stage, but recurrences can be treated successfully, so lifelong
follow-up is most important.

What is the Cause of Thyroid Cancer?

The cause of thyroid cancer is unknown, however, a recognised risk factor is radiation exposure and it has been
found in people who have had external radiotherapy to the neck 10 or 20 years previously as well as in
"Chernobyl children". Research into the causes of thyroid cancer is ongoing. Very occasionally papillary
cancer is hereditary, and medullary cancer is quite often hereditary.
What are the Symptoms of Thyroid Cancer?

• A painless lump in the neck which gradually increases in size. • Difficulty in swallowing (dysphagia) – because of pressure of the thyroid gland on the oesophagus • Difficulty in breathing (dyspnoea) - because of pressure of the thyroid gland and the trachea (windpipe). • Hoarseness of the voice. • Often there are no symptoms and it is found "by chance". • Symptoms of hyperthyroidism (overactive thyroid) and hypothyroidism (under active thyroid) are rare, as cancer cells do not generally affect hormone production from the thyroid.

What tests will I need?

Your GP will do a blood test to see if the thyroid hormone levels are within normal limits. While this does not in
itself diagnose a cancer it does help your GP decide which specialist you will need to see next. Following your
visit to your GP with one of the above symptoms, you will need to have some special investigations to confirm
the diagnosis. These will be done in a specialist hospital clinic.

Fine needle aspiration - This is done in the out-patient hospital clinic. A sample of cells is extracted by means of
a very small needle passed into any swelling you may have in your neck. These cells are then analysed under a microscope. This will be one of the main tests that will help confirm your diagnosis. Blood test- Some additional blood tests may be done to recheck the function of your thyroid and levels of thyroid antibodies. Ultrasound scan - In this test a picture of the thyroid gland is obtained by use of sound waves to show any solid
lumps or cysts. Again this in itself cannot confirm cancer but it can help with the overall diagnosis and in
planning treatment.

Radioisotope scanThis type of scan is occasionally helpful in assessing thyroid lumps. A tuny dose of
radioactive iodine is given as a capsule (or alternatively another radioactive substance called "technetium" is given as an injection), then after a short time a gamma camera is placed over the neck. The camera measures the amount of radioactive substance taken up by the thyroid gland. Cancer cells do not absorb radioactive substances as well as normal thyroid cells, so a small cancer may show on the scan as a 'cold' nodule. However it is not a very good diagnostic test, and many so-called 'cold' nodules are benign.
What Treatment will I be offered?
You may be offered Surgery (thyroidectomy)

Surgery is usually the first line of treatment for thyroid cancer. Usually the whole thyroid gland (total thyroidectomy) will need to be removed, though sometimes it will be adequate to remove only one lobe; it depends on various factors such as your age, size of the lump and results of the tests mentioned above. The parathyroid glands may or may not be removed. After a thyroidectomy, thyroxine tablets will need to be taken as prescribed for the rest of your life; regular blood tests will be needed to check that the thyroid hormone levels are within normal limits, and that the TSH level is suppressed. Eventually you should only need a blood test once or twice a year. Following surgery you will need to have your hormone levels monitored Following your thyroid surgery you will be monitored by your General Practitioner (GP) regarding your thyroid medication and check up blood tests will be done. When you go home please contact your GP or treatment centre if you feel extremely tired, or have feelings of pins and needles in hands/feet/face, or if you have palpitations, feel shaky or become very over-active, or generally feel very unwell. This may mean you need to have your thyroxine or calcium levels checked and your medication dose increased, or decreased as the case may be. Once your body has settled you will be able to lead a normal life but you will need to continue to take the thyroxine tablets for the rest of your life and to have your thyroid tests checked regularly. It will be especially important to have your thyroid tests (TSH) checked if you become pregnant, as you may need to increase your dose of thyroxine (levothyroxine). You will probably also need to have radioactive iodine treatment Most people need to have radioactive iodine treatment following surgery. Your doctor will tell you if this is the case. Radioactive iodine treatment is painless, taken either as one or two capsule-type tablets, or as a liquid, in a single dose. You should not feel sick or lose any hair or have any other side effects with the usual dose required. It is a safe dose of radiation but for the safety of others for the first two to four days a person needs to reduce their social contact and to come into hospital. If you need this treatment you will be informed by your specialist consultant and given an information booklet before you start treatment.
Most thyroid cancers are very treatable and curable

Please contact your Specialist Treatment Centre Staff or your General Practitioner if you have any
questions or concerns after reading this information book. Together we can help you through your
investigations, information, treatment and recovery.

Useful Contacts

The British Thyroid Foundation
PO Box 97 Clifford, Wetherby, West Yorkshire LS23 6XD Tel no: 01423 709707/01423 709448 Butterfly Northeast
PO Box 205, Rowlands Gill , Tyne & Wear NE39 2WX Tel: 01207 545469

Association for Multiple Endocrine Neoplasia Disorders AMEND (MEN2/FMTC)
31 Pennington Place, Southborough, Kent TN4 0AQ

Cancer BACUP
3 Bath Place, Rivington Street, bLondon, EC2A 3JR Tel no: 0800 800 1234

Macmillan Cancer Support
89 Albert Embankment, London SE1 7UQ Freephone 0808 808 2020

Freephone Information Helpline 0800 132905 http://www.personal.u-net.com/ njh/cancer.html CancerHelp UK

Thyroid Cancer Survivors' Association

Other useful sites can be found in the BTA links page

Patient Information Leaflet 2

Thyroid surgery

Your thyroidectomy

What is a thyroidectomy?
A thyroidectomy is the removal of all (total thyroidectomy) or part of the thyroid gland (called
"hemithyroidectomy" or "lobectomy"). You may need to have this done because you have a swelling or
enlarged gland or for thyroid cancer treatment. Your specialist will explain to you whether a part or all of
your thyroid needs to be removed, in order for you to give fully informed consent. If you do not
understand any of the information please ask, as it is very important for you to make the right decision.
Is it a safe operation and what are the side-effects?

• The total removal of the thyroid gland means that you will need to take replacement hormone tablets
called thyroxine every day for the rest of your life, otherwise you will experience symptoms of hypothyroidism (under active thyroid). Thyroxine tablets are the size of a sugar sweetener and safe to take. With monitoring by your specialist centre and or your general practitioner (GP) you should be able to lead an active and normal life. • Thyroxine tablets are also given to suppress the level of TSH, and this is an important part of the treatment for thyroid cancer. So most patients will be given thyroxine even if they have only had part of the thyroid removed. You will be advised on this before you go home from hospital. • You will need regular blood tests to measure the levels of hormones in your blood, and your medication will be adjusted accordingly. You will be given appointments for this. • Thyroidectomy does not affect your ability to have children, but do ask your specialist for advice and information first if you are thinking of starting a family.
Will it affect my voice?

The thyroid gland lies close to the voice box (larynx) and the nerves to the voice box. Following your
surgery you may find that your voice may sound hoarse and weak and your singing voice may be slightly
altered, but this generally recovers quite quickly. In a very small number of cases this can be permanent.
Will my calcium levels be affected following thyroid surgery?

The parathyroids control the levels of calcium in the blood and are found close to the thyroid.
Sometimes these glands are affected during surgery and if that is the case you may experience tingling
sensations in your hands, fingers, in your lips or around your nose. Sometimes people may feel quite
unwell. Please report this to the staff looking after you or, if at home, to your GP. Blood tests will be
taken to monitor the levels of calcium in your blood following surgery. If the level of calcium is falling
this can easily be treated by giving you calcium supplements, which may be given via an intravenous
drip and/or by tablets. You may only need to take these tablets temporarily, as the parathyroids usually
resume normal function following removal of the thyroid. You will be advised by the medical and
nursing staff.
Will I have neck stiffness, restricted shoulder movement or pain?

You will feel some discomfort and stiffness around your neck but you will be given some medication to
help ease any pain and discomfort. Pain relief may be given in different ways, such as injections, liquid
medicine or tablets. Most patients say the discomfort is not as bad as they expected and after the first
day are up and walking around. After the first day following your surgery you will be given some gentle
neck exercises to do; this may be given in an information sheet but please do ask staff if you are unsure.
After a few weeks you should be back to a good standard of neck movement and shoulder function.

Will I have a scar?

Following your surgery, whether all or part of your thyroid is removed, you will have a scar, but once
this is healed it is usually not very noticeable. The scar runs in the same direction as the natural lines of
the skin on your neck
When will the operation be done?

You will probably have attended the out-patient clinic and may have been given a date for your operation
at that time. Otherwise you may receive a date through the post or by phone from your Consultant's
What happens in a pre-admission assessment clinic?

• Some hospitals (not all) run a pre-admission assessment clinic, and you may be invited to attend one
or two weeks before your operation. This enables both the doctors and the nurses to assess your health needs and carry out routine tests which may be required prior to surgery i.e. blood tests, a heart tracing (ECG) and a chest X-ray. • The pre-admission assessment gives you the opportunity to meet the ward staff and to see where you will be admitted on the day of your operation. It is also a time when you can ask questions and discuss any concerns you may have about your operation and coming into hospital. • Time is allocated for each individual and you should expect to be here no longer than 2 hours. However in exceptional circumstances a delay may be unavoidable. • Some patients may have their investigations carried out the day before surgery and in that case would not be asked to attend the pre-admission assessment. What about smoking? All hospitals operate a No Smoking policy and smoking is not allowed on the ward. If you do smoke it is in your own health interests to stop smoking at least 24 hours prior to your anaesthetic. Please contact your GP's surgery for advice on stopping smoking.
What shall I bring into hospital?

• Please bring nightwear, day wear, dressing gown, towels, toiletries, slippers, books/magazines and a
pen. It will be helpful to arrange for a relative or friend to wash your nightwear etc and bring in fresh supplies. Hospital nightwear is available if required.
You must bring with you any medication you are currently taking, including inhalers.
• Please do not bring any valuables with you, such as jewellery, large sums of money or bank cards.
The hospital cannot take responsibility for your valuables. On your admission you will be asked to sign a disclaimer form which gives you the responsibility for any valuables you bring with you. • Valuables may be taken for temporary safe keeping by the ward staff, while you have your operation and you will be issued with a receipt.
Will there be a bed?

• Because the Hospital runs an emergency service, it is not always possible to predict how many beds
will be available. Also operations are carried out every day and clients are discharged home every day. It is therefore difficult to predict early in the morning how many beds will be available. • You may be asked to take a seat in the waiting room until your bed is ready. You may be waiting for another person who has already had an operation to be discharged. The operation lists are planned and it is necessary to operate in a certain order due to many circumstances. It is for this reason that beds are allocated in order of operating lists and not in order of arrival. Please feel free to ask any member of staff for help and advice at any time. We will do our best to accommodate you and to keep you waiting for the least time possible. What instructions or help will I have to get ready for surgery? • Before your operation: when you have been taken to your bed the nurse will welcome you and check your details. It is necessary for you to wear a special theatre gown for your operation. This will be given to you by the nurse and she will show you how to wear it and give assistance if required. • Please only wear cotton pants / underpants under your gown. All other underwear must be removed to ensure your safety during the use of the equipment in the operating theatre. • You will also be given a pair of white elastic stockings to wear during and after the operation which will prevent blood clots forming in your legs. They feel quite tight and you may need help in putting them on.
What preparation will I need for the operation?

• Your operation will be carried out under a general anaesthetic which means that you are fully
unconscious for the whole operation. Removing all or part of the thyroid involves delicate surgery which means that the operation can take about two hours. • To prevent vomiting and other complications during your operation it is necessary that you should starve for at least 6 hours prior to your operation. You will be advised of what time you should starve from when you attend the pre-admission assessment or by letter from the Consultant's secretary. • You should expect to be in hospital for about 4 days, or longer if any complications arise. • If you would like to meet another patient who has had a thyroidectomy this can sometimes be
What will happen when I go to theatre?

• Just before going to theatre a checklist is completed by the nurse. You will then be taken on your bed
to the operating theatre, usually by a theatre technician and a nurse. The nurse will stay with you in the anaesthetic room. • Dentures, glasses and hearing aids can be taken out in the anaesthetic room and taken back to the ward by the nurse or you may like to put them in your locker before your operation. • The anaesthetist will insert a small needle into the back of your hand through which you will be given the anaesthetic. The nurse will stay with you until you are fully under the anaesthetic and fully asleep. You will not wake up until the operation is over. You will be taken, on your bed, to the recovery area where a nurse will look after you until you are awake. You will then be taken back to the ward, on your bed, by a theatre technician and a nurse.

What will happen when I get back on the ward following surgery?

• Back on the ward you will be made comfortable. You will be sitting fairly upright in your bed
supported by several pillows as this will help to reduce any neck swelling. Your nurse call bell will be situated close to you so that you can call a nurse at any time. • You will have your blood pressure, pulse and oxygen levels checked frequently. A machine will do this automatically -- a blood pressure cuff is wrapped around your upper arm and a probe is clipped to one of your fingers. • There will be a fluid drip going into a vein, probably in the back of your hand; this will be removed as soon as you are drinking normally (usually within 24 hours). You will be able to sip drinks quite soon after your operation as long as you are not feeling sick, and you can eat as soon as you feel you are able.
What will I look like after thyroid surgery and what will I be able to do?

• You will have a scar on the front part of your neck which will feel a little tight and swollen initially
after the operation. It may feel a bit sensitive but should not cause any distress. • You may have one or two wound drains from your wound to collect wound fluid which naturally occurs following your surgery. The drains are small plastic tubes which are inserted into the neck at the end of your operation. The long length of tubing outside the neck is attached to a plastic collection bottle into which the fluid drains. Wound drains help to speed up wound healing and reduce infection. The drains are not painful and you can carry them around with you. The drains will be removed by a nurse and they are usually removed when the drainage is very minimal. The time span may vary but is usually a day or two after your operation. • You will feel some discomfort and stiffness around your neck but you will be given some medication to help ease any pain and discomfort. Pain relief may be given in different ways such as injections, liquid medicine or tablets. Other patients say it is not as bad as they expected and after the first day are up and walking around. • For your own safety it is important that you do not get out of bed on your own immediately following your operation as you may be drowsy and weak. At first when you need to use the toilet a member of staff will need to assist you with a commode or bedpan. You will soon be able to walk to the bathroom yourself. • You will have a nurse call bell within easy reach so that you can seek help from the ward staff as
• Following your operation you may not feel very sociable so it is wise to restrict visitors.

Will it affect my eating and drinking?

For a short period after your operation you may find it painful to swallow and you may need a softer diet
for a short time. You may find that nutritious drinks are helpful in maintaining a balanced diet which is
important to assist healing.

Will I have a sore neck?

You will probably find that your neck is quite sore and you will be given medication to take home to
relieve the discomfort. Please take your medication as described on the packet and take care not to
exceed the recommended number of tablets.

This medication should also ease the discomfort on swallowing. Your neck may appear swollen and
hard to touch, with some numbness, which will gradually resolve as healing takes place.

What should I do to reduce any risk of wound infection?

Keep you neck wound clean and dry. Initially the nursing staff will check your wound daily and clean it
as necessary. A few days following surgery when you are feeling more recovered you may have a shower
or bath but take care to ask the nursing staff's advice first and gently pat the wound dry with a clean
towel. Exposure to the air will assist wound healing.
If your neck becomes increasingly painful, red or swollen or you notice any discharge then please seek
medical advice from ward staff or GP. To reduce the risk of infection it is wise to avoid crowded places
and take extra care of yourself. Use only clean towels on your wound area for the first few weeks.

What care do I need to take regarding my neck wound?

Take care not to knock your wound and remember to keep it dry if it becomes wet after bathing or
showering by patting it dry with a clean towel.
Once the scar has begun to heal, you can rub a small amount of unscented moisturising cream on the
scar so it is less dry as it heals. Calendula, Aloe Vera or E45 cream (available from health shops) are
effective. The pressure of rubbing the cream in will also help to soften the scar.

What rest do I need?

You will need to take it easy while your neck wound is healing. This means avoiding strenuous activity
and heavy lifting for a couple of weeks. Your neck will gradually feel less stiff and you will soon be able
to enjoy your normal activities.

What about my medications and tablets?

Please continue to take the medication you have been prescribed and ensure that you have a good supply.
If you are unsure about any of the tablets you need to take please check this with a nurse before you go
home. Repeat prescriptions can be obtained from your GP. When you come for your appointments at
the hospital to check your blood levels following your thyroidectomy your medication may need to be
altered so please check with the medical staff.

When should I return to work?

You will probably need to take 1-2 weeks off work (or sometimes longer) depending on your occupation
and the nature of your work. The hospital can issue you with a note for 2 weeks and then you should see
your GP if more time is required.
Will I need to be checked in an out-patient department following discharge home?

Following your discharge you will need to be reviewed in the out-patient clinic to check how your
wound is settling down, your hormone levels and how you are feeling. You will usually receive the date
and time for this appointment through the post or it may be given to you by the ward staff before you go
home. Please contact the ward or the Consultant's secretary at the hospital if you do not receive one
shortly following discharge. Depending on the problem with your thyroid and the results from the thyroid
tissue that has been removed, you may be offered further treatment. This will be discussed with you by
your specialist Consultant at your clinic appointment. If you would like any further information please
do not hesitate to ask the nursing staff.

Will I be able to cope?

Most people when first told they need to have a thyroidectomy say they feel all sorts of mixed emotions,
while others feel numb, some feel they knew all the time that they would need surgery. We are all
individuals and cope in different ways and need different lengths of time to adjust to the changes we
You do not have to face your treatment on your own.
Support and help is available from the staff.
Together we can help you through your investigations treatment and recovery.

Useful Contacts

The British Thyroid Foundation
PO Box 97 Clifford, Wetherby, West Yorkshire LS23 6XD Tel no: 01423 709707/01423 709448 Butterfly Northeast
PO Box 205, Rowlands Gill , Tyne & Wear NE39 2WX Tel: 01207 545469

Association for Multiple Endocrine Neoplasia Disorders AMEND (MEN2/FMTC)
31 Pennington Place, Southborough, Kent TN4 0AQ

Cancer BACUP
3 Bath Place, Rivington Street, bLondon, EC2A 3JR Tel no: 0800 800 1234

Macmillan Cancer Support
89 Albert Embankment, London SE1 7UQ Freephone 0808 808 2020

Freephone Information Helpline 0800 132905 http://www.personal.u-net.com/ njh/cancer.html CancerHelp UK

Thyroid Cancer Survivors' Association

Other useful sites can be found in the BTA links page
Patient Information Leaflet 3
Radioactive iodine ablation and therapy
Things you need to know
Radioactive iodine "ablation" is treatment with radioactive iodine, intended to kill off any remaining
thyroid tissue in the neck after a thyroid operation. Radio active iodine "therapy" refers to treatment with
radioactive iodine with the intention to kill off thyroid cancer cells in the neck or elsewhere in the body.
Radioactive iodine therapy is given only if the tests show that there is persistent tumour in the body.
Most of what follows applies to both "ablation" and "therapy" and will be referred to as "radioactive
iodine treatment".
This form of treatment (ablation or therapy) consists of swallowing radioactive iodine either as a capsule
or a liquid. The radioactive iodine is taken up by the thyroid gland. The very small dose of radiation is
then concentrated in the thyroid cells and destroys them.
Is radioactive iodine treatment (ablation or therapy) safe?

Radioactive iodine has been used to treat thyroid cancer for over 50 years. The greatest danger from
radioactive iodine is to the thyroid gland, but as your thyroid has been removed, it is not at risk; the
treatment is meant to destroy any thyroid cells that may have escaped surgical removal. Radioactive
iodine treatment has been linked with an increased risk of developing other cancers. In absolute terms,
this risk is small, and has to be balanced against the benefits in treating the thyroid cancer. Your
consultant will discuss these issues with you in detail before the treatment.
The precautions which are described below are intended to protect other people, and particularly
pregnant women and young children. It makes sense to reduce everyone's exposure to radioactivity, as
any one of us may need this form of treatment in the future.
Are there any side effects from radioactive iodine treatment?

Most patients do not have side effects form radioiodine treatment. Some patients may experience a feeling of
tightness in the throat and/or feel flushed, which usually lasts for no more than 24 hours. If this persists please
inform the nursing staff. An anti-inflammatory drug can be given to relieve this problem. Some patients may
lose their taste slightly. This can happen a few weeks after the treatment and should only last a few days.
Drinking plenty of water after the treatment helps to wash out the radioactivity and reduces this problem. Please
do talk through any of your questions with the specialist consultant or a member of the treatment team.
What if I am pregnant or feeding?

It is very important that you do not have radioactive iodine treatment if you are pregnant, or think there is
a good chance that you may be. Please let your medical staff know if you are unsure before you have any
treatment. It is important not to become pregnant when having investigations for thyroid cancer. You
should use a reliable contraceptive for at least 6 months after radioactive iodine treatment. Long term,
your fertility will not be affected even after repeated doses of radioactive iodine.
If you are breast feeding, you should stop this at least 4 weeks and preferably 8 weeks before you have
the radioiodine treatment and not be restarted.

(Male patients) Will it affect my ability to have children?

Male patients are advised not to try for children (get their partners pregnant) for 4 months following
radioactive iodine treatment and until they are sure they will not need any further radioactive iodine
treatment. Long term your fertility should not be affected but there may be a small risk if repeated
radioactive iodine therapy is needed. Please discuss this with your specialist consultant or a member of
the treatment team before trying for a family following this treatment: specialist advice and help is

Before having radioactive iodine treatmenty what medication/tablets should I take?

If you are taking T3 tablets, most specialist centres recommend these should be stopped for
2 weeks before your radioactive iodine treatment.
If you are on levothyroxine tablets most specialist centres will advise you to stop taking them for 4 weeks before
the radioactive iodine treatment. In this 4 week period your specialist may first change you to T3 tablets for 2
weeks, and then stop your tablets altogether for the last 2 weeks before your treatment. You may feel weak and
tired when you are not taking your tablets. This is normal and will disappear once you start taking them again,
usually a few days after you have had your radioiodine.
It is important that you follow the instructions regarding stopping your thyroxine medication given to you
by your specialist centre staff, as it may vary in different centres. Please contact your specialist centre if
you are unsure about your thyroxine medication, one month before your planned date for radioactive
iodine treatment.
Should I keep taking my other medication/tablets?

If you are taking any other tablets you should carry on doing so and bring a supply with you on admission and
show them to the doctor and nurse team. If you are taking any vitamin or mineral supplements or cod liver oil
stop taking them around three weeks before your therapy to help reduce your iodine levels.
Before my Radioactive Iodine Therapy what should I eat?

A diet which is rich in iodine can reduce the effectiveness of the treatment. Therefore two weeks before
coming in to hospital we recommend the following:
Do eat fresh meat, vegetables, fresh fruit, pasta and rice. These are low in iodine.
Do not eat glace and maraschino cherries which contain the colouring material E127. Food
coloured by spices is allowed. • Do not take cough medicine, iodised table salt, or sea salt as these contain iodine. Ordinary table
salt is allowed. • Try to cut down on dairy produce such as eggs, cheese, milk and milk products, as they all
contain some iodine. • Avoid fish, kelp and all seafood.
Avoid vitamin supplements which contain iodine.

Do I have to come into hospital for radioactive iodine treatment?

Yes, you will probably need to stay in hospital for 3-6 days. How soon you go home depends on how
quickly the radioactivity leaves your body.

What happens on admission?

On the ward you will be greeted and your details will be registered. You will then be issued with a
hospital name band to wear, with your hospital registration number and a few details on it. One of the
nursing staff will take your blood pressure, pulse and temperature as a routine procedure.
You will be given an explanation of the treatment and details about the room you will be staying in.
You will have the opportunity to ask any questions that you might have.
Your doctor will then come to examine you and check that you have stopped taking your thyroid tablets
prior to the treatment, as this interferes with the absorption of the radioactive iodine. You will have been
sent information regarding this with your appointment letter.
You will be asked to sign a form giving consent for the treatment.

Who gives the Capsule?

The Nuclear Medicine (or Medical Physics) department within the hospital is responsible for dealing with the
radioiodine treatment. One of their staff will come to the ward to give you the capsule (which is about the size
of an antibiotic capsule), or the liquid (which is colourless and tasteless.

What happens next?

For the first two hours after taking the capsule you should refrain from eating and drinking, to allow time for the
iodine to be absorbed.m After this time you should eat as normal and drink as much as possible and so that you
pass urine frequently. This will flush the excess radioactive iodine out of your system.

Are there any restrictions?

As the treatment you have received is radioactive no young children or pregnant women are allowed to
visit. Others may visit for a short time. Because you are radioactive, staff will spend only short periods
of time in your room. When they bring in your meals and drinks they may stand behind a lead screen
and you should try to remain on the opposite side of the room. Do not expect them to stay and chat for
long periods of time but do not hesitate to contact them if you need anything.

What happens at mealtimes?

The nursing staff will bring you meals in your room. These meals may be served on paper plates and
you may need to use plastic cutlery. When you have finished your meal these should be disposed of in a
bin provided. If there is any unwanted food this needs to be sealed in a plastic bag and disposed of in the
bin. Alternatively, if ordinary plates and cutlery are used these will have to be washed up either in your
room, or in a special kitchen. A waste disposal unit may be available to dispose of any unwanted food.
Each day you will receive a menu to fill in for the next day. Drinks are provided in the morning, mid-
morning, lunch time, tea time and night time. If you do not receive your meal for whatever reason please
ring the nurses station, who will provide you with one. We will try our best to ensure this does not

What self washing/hygiene should I do?

As you should be drinking a lot, you should also be using the toilet frequently. All your bodily fluids are
radioactive so you must flush the toilet after use. If you spill or splash urine please contact the nursing
Your sweat is also radioactive, so we advise you take a bath or shower daily. This may sound a little
strange and alarming at first but please remember this is a safe dose of radiation and it is for your
treatment and long term recovery.

Are there any other items I can bring in with me to help me relax or pass the time?

You may have brought DVDs, CDs, laptops, iPods, books, clothes and toiletries with you. These items
may need to be monitored for contamination before they can be removed from your room. It may
sometimes be necessary for us to keep some of your belongings if they are contaminated. They will be
returned to you once they are no longer contaminated.

When can I go home?

The staff from Nuclear Medicine or Medical Physics will come to the ward to take measurements and
they can then work out how much radiation is still in your body and if you are at a safe level to go home.
You must stay in the iodine room until that time. Before going home you may have a whole body scan.

Will I still have any restrictions when I get home?

The Nuclear Medicine or Medical Physics staff will explain to you the restrictions you must observe
when you go home, for example avoiding crowded places and limiting the people you come into contact
with. They can work out exactly how many days you need to restrict yourself. The restrictions you are
given may vary from other patients as some patients may be lower or higher in their radioactivity. You
will be at an acceptable level to go home. These restrictions are to protect other people, specially
pregnant women and children.
Medical or nursing staff will organise a new supply of thyroid tablets for you to take home and you will
be told when to restart them .

Will I have to come back to the hospital?

You will need to be seen again in the outpatient department by your doctor. You will either be given an
appointment when you leave the ward, or this may be sent to you later.
When everything is organised you are free to go home.
Will I need Radioactive Iodine treatment again?

The treatment may need to be repeated until all the remaining thyroid tissue has been destroyed. Some
people require one ablation dose and some people require more than one treatment.
Please remember that this is a low dose of radiation and all these procedures are to protect you and others
in case they should need to have radiation treatment in the future. The aim is to keep everybody's
exposure to a minimum.

Please contact your specialist treatment centre staff if you have any questions or concerns after reading
this Information book. Together we can help you through your investigations, treatment and recovery.

Useful Contacts

The British Thyroid Foundation
PO Box 97 Clifford, Wetherby, West Yorkshire LS23 6XD Tel no: 01423 709707/01423 709448 Butterfly Northeast
PO Box 205, Rowlands Gill , Tyne & Wear NE39 2WX Tel: 01207 545469

Association for Multiple Endocrine Neoplasia Disorders AMEND (MEN2/FMTC)
31 Pennington Place, Southborough, Kent TN4 0AQ

Cancer BACUP
3 Bath Place, Rivington Street, bLondon, EC2A 3JR Tel no: 0800 800 1234

Macmillan Cancer Support
89 Albert Embankment, London SE1 7UQ Freephone 0808 808 2020

Freephone Information Helpline 0800 132905 http://www.personal.u-net.com/ njh/cancer.html CancerHelp UK

Thyroid Cancer Survivors' Association

Other useful sites can be found in the BTA links page

Source: http://www.thyroidcancer.ru/med/literature/guides/draft_thyca_23.12.06.pdf

The acupuncture treatment of alcohol and chemical dependency

JOURNAL OF CHINESE MEDICINE NUMBER 45 MAY 1994 The Acupuncture Treatment of ALCOHOL AND CHEMICAL by David Blow Dip.App.Sc. (Acup.) We are still a long way from being able to say thousands of patients that experience relief of acute that acupuncture and the treatment of chemi- withdrawal symptoms, find their will power is strength-

Jewish american and holocaust literature

ALAN L. BERGER AND New beginnings always occasion reflection on the past. This inexo- rable rule of human behavior applies especially to the cultural realm whereinnovation is in constant, and frequently creative, tension with what hasgone before. Thus, the dawn of the new millennium is an appropriate momentto view two related literary genres, which have to a large extent shapedtwentieth-century literature. Jewish American and Holocaust literature to-gether have confronted, and reflected on, the meaning of being human, theplace of tradition in modernity, the content of Jewish identity, the issue ofmemory, the nature of evil, and the role of God in history. Further, thequestions raised by these genres have both particular and universal reso-nance. Composed against a tumultuous background of great cultural transi-tion and unprecedented state-sponsored systematic murder, this literatureaddresses the concerns of human existence in extremis.