- Email: [email protected]
Goitre and thyroid cancer
THYROID
Goitre and thyroid cancer
iodine excess: iodine-excess goitre is seen in areas of Japan where seaweed and fish are heavily consumed goitrogenic drugs and foods, such as chronic therapeutic lithium and consumption of vegetables which metabolize to the goitrogen thiocyanate (e.g. the Brassica family). The pathogenesis of benign goitres in iodine-replete areas remains incompletely understood although a small persistent increase in thyroid-stimulating hormone (TSH) coupled with even a marginal iodine deficiency is thought to lead to thyrocyte proliferation and thyroid gland enlargement, particularly if this occurs in youth.3 The nodules that subsequently form possess a differential sensitivity to TSH stimulation, culminating in nodule autonomy.4 Risk factors for thyroid malignancy are: a family history B medullary thyroid cancer in the context of MEN2 syndrome 5 B familial papillary and follicular thyroid cancer exposure to radiation B evidence from survivors of the atomic bombs dropped on Japan in 1945 and the Chernobyl accident in 1986 confirm the cancerogenous effect of radiation, which appears to be most damaging if exposure occurs in youth and coupled with iodine deficiency6 B the foetuses in pregnant women exposed to radiation in Chernobyl were also at an increased risk of thyroid malignancy in later life.7 Irrespective of the type of thyroid cancer and the perceived aetiology of the disease, one of the key molecular pathogenetic events lies in the activation of the ret (rearranged during transfection) protooncogene.
Fausto Palazzo
Abstract Thyroid enlargement is common and thyroid malignancy rare, but the clinical presentation of benign and malignant disease are similar. The aim of clinical assessment and investigations is to identify the small number of cancers amongst the non-malignant thyroid enlargements. Investigations include thyroid function tests and fine-needle aspiration cytology. Benign thyroid disease needs treatment only in the presence of dysfunction or local compressive symptoms. The treatment of thyroid cancer is multidisciplinary and includes surgery, radioiodine therapy and lifelong thyroidstimulating hormone suppression. The diagnosis and management of thyroid cancer is being centralized around the multidisciplinary team in order to improve the outcomes in the UK.
Keywords goitre; thyroid cancer; thyroid nodule
The term goitre describes any enlargement of the thyroid gland. It may be caused by a solitary nodule (Figure 1) or multiple nodules (Figure 2), or by a smooth enlargement of some or all of the gland. Goitres may be classified on the basis of epidemiology, aetiology, anatomical and morphological features or functional status (Table 1) or a combination of these criteria (Table 2). Worldwide the most common form is an endemic goitre secondary to iodine deficiency, which is described as such because the prevalence is greater than 5% in children under the age of 12 years (within a community or geographical area). The term sporadic is used if this condition is not met. Palpable thyroid nodules and/or goitre are found in up to 7% of the population in iodine-replete areas. Sub-clinical ultrasound-detected thyroid nodules are found in 45% of women and 32% of men at 55 years.1 Thyroid cancer represents 1% of newly diagnosed cancers and is the most common endocrine malignancy, with a growing incidence of up to 5 per 100,000 per annum. The challenge for the clinician lies in the need to identify the relatively small number of cancers in a gland where there are frequently benign thyroid nodules.
Clinical presentation History Most goitres are found incidentally by the patient, by the general practitioner or at radiological examination.8 Nodules occur at all ages and in both sexes but those presenting in men or at the extremes of age should be treated with greater suspicion. A short history of rapid enlargement in the elderly is suggestive of malignancy whilst in the young bleeding into a nodule or cystic enlargement may be responsible for this. A slow history of
Aetiopathogenesis of goitre The most common causes of goitre are: iodine deficiency: the prevalence of endemic goitre should decrease with iodine supplementation programmes2
Fausto Palazzo MS(Lon) FRCS(Eng) FRCS(Gen) is a Consultant Endocrine Surgeon at Hammersmith & Charing Cross Hospitals, UK. Competing interests: organizes an annual multidisciplinary endocrine surgical symposium that is sponsored by pharmaceutical companies; none are related to thyroid disease. Also is paid a lecturing fee to teach thyroid surgical technique annually at the European Surgical Institute funded by Ethicon.
MEDICINE 37:8
Figure 1 A solitary nodule later found to be malignant on thyroid cytology.
436
Ó 2009 Elsevier Ltd. All rights reserved.
THYROID
Combined goitre classification Type of goitre
Example
Simple euthyroid Diffuse goitre goitre (sporadic/endemic) Multinodular goitre Toxic goitre Solitary toxic nodule Toxic multinodular (Plummer’s) Diffuse autoimmune (Graves’) Thyroiditis Subacute (de Quervain’s) Autoimmune (Hashimoto’s) Riedel’s Neoplasia Adenoma Carcinoma (primary/metastasis) Others Amyloidosis Chronic bacterial infection (TB/syphilis) Actinomycosis
Figure 2 A large multinodular goitre causing local compression.
enlargement does not allow the exclusion of malignancy on clinical grounds alone. The presence of local compressive symptoms (dysphagia and dyspnoea) should be enquired about specifically. Dysphonia in the presence of a goitre is suggestive of thyroid malignancy invading the recurrent laryngeal nerve and causing vocal cord paralysis. Local compressive-type symptoms disproportionate to the size of the goitre, especially if coinciding with pain, should alert to the possibility of thyroiditis. The presence of symptoms of hyperthyroidism e weight loss, tremor, anxiety, insomnia, etc. e is suggestive of toxicity and has been discussed above. Specific malignancy risk factors should be enquired about e a family history and a history of radiation exposure. Suspicion of medullary thyroid cancer requires a focused history regarding MEN2 syndrome (e.g. phaeochromocytoma and hyperparathyroidism).
Table 2
Examination Neck examination is conventionally performed from behind, with the patient seated. Any neck lump in the anterior triangle of the neck that rises and descends on swallowing is thyroidrelated. Once the clinical thyroid status has been established the neck lump is examined with a view to establishing its size, shape, margins, consistency, tenderness and mobility. It is also necessary to establish whether this is a solitary/dominant nodule or the smooth enlargement of the whole gland. Hard nodules with poorly defined margins raise suspicions of malignancy but Hashimoto’s thyroiditis may also be both firm and ill-defined. In all patients the presence or absence of cervical lymphadenopathy should be established.
Investigation of a goitre
Goitre classifications Criterion
Groups
Epidemiology
Endemic Sporadic Familial
Aetiology
Iodine deficiency Graves’ disease Hashimoto’s thyroiditis (in enlargement phase) Neoplasia Goitrogenous nutrients and drugs (thiocyanates, lithium) Dyshormonogenesis
Morphology Anatomy
Laboratory investigations The essential tests to be performed are the thyroid function tests: TSH, T3 and T4. In addition, a number of accessory tests can be performed. These are: thyroid autoantibody levels, if there is a suspicion of autoimmune thyroid disease or if a lymphoma is suspected (the latter occurs almost exclusively on a background of Hashimoto’s thyroiditis) calcitonin estimation, where medullary thyroid cancer is suspected. Fine-needle aspiration cytology Fine-needle aspiration cytology is the investigation of choice in solitary and dominant thyroid nodules. The procedure is performed by the clinician or under ultrasound guidance for small, less well-defined or awkwardly placed nodules.9 The investigation is well tolerated and provides excellent levels of preoperative diagnosis. Increasingly the Thy1e5 classification is adopted in the UK and forms the basis for treatment (Table 3).
Diffuse Multinodular Cervical Retrosternal
Functional status Euthyroid Toxic
Radiological investigations Radiological investigations are requested with a view to asking a specific question.
Table 1
MEDICINE 37:8
437
Ó 2009 Elsevier Ltd. All rights reserved.
THYROID
Thy1e5 classification of thyroid cytology Cytology
Description
Action
Thy1 Thy2 Thy3
Non-diagnostic smear Non-neoplastic/benign Follicular lesion/suspected follicular neoplasm
Thy4
Suspicious (but not absolutely diagnostic) of papillary, medullary or anaplastic carcinoma, or lymphoma) Diagnostic of malignancy (unequivocal features of papillary, medullary or anaplastic carcinoma, lymphoma or metastatic tumour)
FNA should be repeated Repeat to confirm diagnosis within 6 months Most of these patients should be treated by surgical removal of the lobe for diagnosis Surgical intervention is indicated or the aspirate should be repeated
Thy5
Surgical intervention is indicated for nearly all primary tumours except lymphoma and anaplastic cancer
FNA: fine-needle aspiration.
Table 3
Thyroid ultrasound scanning: ultrasound is rarely independently diagnostic but may be used to guide fine-needle aspiration cytology. Ultrasonographic criteria for thyroid malignancy may add weight to clinical and/or cytological findings. It is also excellent at assessing for the coexistence of cervical lymphadenopathy.
Thyroid malignancy Given the rarity of thyroid cancer it is best managed in a multidisciplinary team context in regional centres. Thyroid malignancies are classified according to the cell of origin:
CT and MRI scanning of goitres: cross-sectional imaging (magnetic resonance imaging (MRI) or computed tomography (CT)) is indicated when the extent of the goitre or tracheal compression are in doubt at clinical examination. Airway compression may be confirmed using the respiratory flowevolume loop.
Accounts for 85% of thyroid malignancy. All age groups, more common in women in young middle age. Tendency to be multifocal, can be locally invasive and spreads to regional lymph nodes even when the cancers are of small size.13
Thyrocytes Papillary thyroid cancer (PTC)
Treatment
Surgery is the primary mode of treatment e extent is dependent on the size of the primary tumour and the evidence of lymph node metastasis. There is a general trend towards a more comprehensive surgical approach, including lymphadenectomy of the central compartment of the neck in all but low-risk patients.14 Radioiodine therapy is recommended in all high-risk patients. Lifelong follow-up with TSH suppression to reduce the risk of recurrence.15 Prognosis: with the appropriate treatment most PTC patients do well with up to 10% dying of their disease.16
Radionuclide imaging: most thyroid malignancies do not concentrate radioisotopes (and thus appear ‘cold’), whereas hot nodules are associated with a low incidence of malignancy. However, less than 20% of cold nodules turn out to be cancers, the remaining 80% resulting from colloid nodules, haemorrhage, cysts or inflammatory lesions. Scintiscanning has therefore been abandoned in euthryoid patients and has been replaced by fine-needle cytology.10
Treatment of multinodular goitre and thyroid malignancy Multinodular goitres Euthyroid asymptomatic benign multinodular goitres do not require treatment unless there is a clinical suspicion or a history of childhood radiation exposure.11 Patients with local compressive symptoms are best served by surgery since the use of suppressive doses of thyroxine to halt or delay the goitre progress usually fails. Retrosternal goitres arguably require surgical intervention, based on the risk of acute or chronic airway obstruction, the malignancy risk in a place that is difficult to monitor and because direct questioning suggests that most patients are symptomatic. This surgical dogma, however, does not stand up to the rigour of an evidence-based analysis, so patients are best considered on a case-by-case basis.12 The threshold for surgery in younger patients with goitres is lower since these patients are more likely to become symptomatic.
MEDICINE 37:8
Follicular thyroid cancer (FTC)
10% of thyroid malignancy. Affects an older age group. Diagnosis requires histological analysis of capsular and vascular invasion so cytology identifies only potential follicular neoplasms. Haematogenous spread is preferred over lymphatic spread (<5%). Treatment
Thyroidectomy extent determined by tumour size and invasion. Radioiodine ablation and lifelong TSH suppression therapy with follow-up as for PTC is required. The less favourable prognosis of FTC is mainly related to the older age group affected.
438
Ó 2009 Elsevier Ltd. All rights reserved.
THYROID
Hurtle cell carcinoma
2 Gaitan E. Intervention policy in endemic goitre areas. Thyroid 1990; 2: 113. 3 Dumont JE, Ermans AM, Maenhaut C, Coppe´e F, Stanbury JB. Large goitre as a maladaptation to iodine deficiency. Clin Endocrinol (Oxf) 1995; 43: 1. 4 Kopp P, Kimura ET, Aeschimann S, et al. Polyclonal and monoclonal thyroid nodules co-exist within human multinodular goitres. J Clin Endocrinol Metab 1994; 79: 134. 5 Kebebew E. Hereditary non-medullary thyroid cancer. World J Surg 2008; 32: 678e82. 6 Nakachi K, Hayashi T, Hamatani K, Eguchi H, Kusunoki Y. Sixty years of follow-up of Hiroshima and Nagasaki survivors: current progress in molecular epidemiology studies. Mutat Res 2008; 659: 109e17. 7 Hatch M, Brenner A, Bogdanova T, et al. A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to Iodine-131 from Chernobyl fallout. In utero exposure to Iodine-131 from Chernobyl. J Clin Endocrinol Metab 2009; 94: 899e906. 8 Gough J, Scott-Coombes D, Palazzo FF. Thyroid incidentaloma: an evidence-based assessment of management strategy. World J Surg 2008; 32: 1264e8. 9 Danese D, Sciacchitano S, Farsetti A, Andreoli M, Pontecorvi A. Diagnostic accuracy of conventional versus sonography-guided fineneedle aspiration biopsy of thyroid nodules. Thyroid 1998; 8: 15e21. 10 Giuffrida D, Gharib H. Controversies in the management of cold, hot and occult thyroid nodules. Am J Med 1995; 99: 642e50. 11 Levy EG, Greenlee C, Mandel S, Kaplan M. Should you always trust FNA interpretations? Thyroid 2000; 10: 279. 12 White ML, Doherty GM, Gauger PG. Evidence-based surgical management od substernal goiter. World J Surg 2008; 32: 1285e300. 13 Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003; 13: 381e7. 14 Palazzo FF, Gosnell J, Savio R, et al. Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades. Eur J Surg Oncol 2006; 32: 340e4. 15 British Thyroid Association. BTA Guidelines for the management of thyroid cancer, 2nd edn, 2008. Also available from: http://www. british-thyroid-association.org (accessed 22.05.09). 16 Hay ID, Klee GG. Thyroid cancer diagnosis and management. Clin Lab Med 1993; 13: 725.
Uncommon. Tendency to more aggressive behaviour. Treatment
Similar to an aggressive PTC. Total thyroidectomy and central compartment lymphadenectomy. Radioiodine therapy less likely to be effective due to the lower uptake in these tumours. Anaplastic carcinomas
Uncommon dedifferentiated devastatingly aggressive variant of PTC. Affects patients in their sixth decade onwards: history of dramatic increase in goitre size. Few survive more than 3 months. Best results are achieved using a combination of surgery, external irradiation and chemotherapy. Parafollicular C cells Medullary thyroid cancer (MTC)
Sporadic or part of MEN2 syndrome. Spreads via lymphatics. Treatment
Comprehensive thyroid and lymph node surgery. Radioiodine not taken up. Thyroidal lymphocytes
Lymphoma: uncommon and occurs almost exclusively in patients with a history of autoimmune thyroiditis. The treatment is chemo-radiotherapy, which can be curative in localized disease. Metastases (rare)
Renal, breast, uterine and melanoma.
A
REFERENCES 1 Reiners C, Wegscheider K, Schicha H, et al. Prevalence of thyroid disorders in the working population of Germany: ultrasonography screening in 96,278 unselected employees. Thyroid 2004; 14: 926e32.
MEDICINE 37:8
439
Ó 2009 Elsevier Ltd. All rights reserved.
Goitre and thyroid cancer
iodine excess: iodine-excess goitre is seen in areas of Japan where seaweed and fish are heavily consumed goitrogenic drugs and foods, such as chronic therapeutic lithium and consumption of vegetables which metabolize to the goitrogen thiocyanate (e.g. the Brassica family). The pathogenesis of benign goitres in iodine-replete areas remains incompletely understood although a small persistent increase in thyroid-stimulating hormone (TSH) coupled with even a marginal iodine deficiency is thought to lead to thyrocyte proliferation and thyroid gland enlargement, particularly if this occurs in youth.3 The nodules that subsequently form possess a differential sensitivity to TSH stimulation, culminating in nodule autonomy.4 Risk factors for thyroid malignancy are: a family history B medullary thyroid cancer in the context of MEN2 syndrome 5 B familial papillary and follicular thyroid cancer exposure to radiation B evidence from survivors of the atomic bombs dropped on Japan in 1945 and the Chernobyl accident in 1986 confirm the cancerogenous effect of radiation, which appears to be most damaging if exposure occurs in youth and coupled with iodine deficiency6 B the foetuses in pregnant women exposed to radiation in Chernobyl were also at an increased risk of thyroid malignancy in later life.7 Irrespective of the type of thyroid cancer and the perceived aetiology of the disease, one of the key molecular pathogenetic events lies in the activation of the ret (rearranged during transfection) protooncogene.
Fausto Palazzo
Abstract Thyroid enlargement is common and thyroid malignancy rare, but the clinical presentation of benign and malignant disease are similar. The aim of clinical assessment and investigations is to identify the small number of cancers amongst the non-malignant thyroid enlargements. Investigations include thyroid function tests and fine-needle aspiration cytology. Benign thyroid disease needs treatment only in the presence of dysfunction or local compressive symptoms. The treatment of thyroid cancer is multidisciplinary and includes surgery, radioiodine therapy and lifelong thyroidstimulating hormone suppression. The diagnosis and management of thyroid cancer is being centralized around the multidisciplinary team in order to improve the outcomes in the UK.
Keywords goitre; thyroid cancer; thyroid nodule
The term goitre describes any enlargement of the thyroid gland. It may be caused by a solitary nodule (Figure 1) or multiple nodules (Figure 2), or by a smooth enlargement of some or all of the gland. Goitres may be classified on the basis of epidemiology, aetiology, anatomical and morphological features or functional status (Table 1) or a combination of these criteria (Table 2). Worldwide the most common form is an endemic goitre secondary to iodine deficiency, which is described as such because the prevalence is greater than 5% in children under the age of 12 years (within a community or geographical area). The term sporadic is used if this condition is not met. Palpable thyroid nodules and/or goitre are found in up to 7% of the population in iodine-replete areas. Sub-clinical ultrasound-detected thyroid nodules are found in 45% of women and 32% of men at 55 years.1 Thyroid cancer represents 1% of newly diagnosed cancers and is the most common endocrine malignancy, with a growing incidence of up to 5 per 100,000 per annum. The challenge for the clinician lies in the need to identify the relatively small number of cancers in a gland where there are frequently benign thyroid nodules.
Clinical presentation History Most goitres are found incidentally by the patient, by the general practitioner or at radiological examination.8 Nodules occur at all ages and in both sexes but those presenting in men or at the extremes of age should be treated with greater suspicion. A short history of rapid enlargement in the elderly is suggestive of malignancy whilst in the young bleeding into a nodule or cystic enlargement may be responsible for this. A slow history of
Aetiopathogenesis of goitre The most common causes of goitre are: iodine deficiency: the prevalence of endemic goitre should decrease with iodine supplementation programmes2
Fausto Palazzo MS(Lon) FRCS(Eng) FRCS(Gen) is a Consultant Endocrine Surgeon at Hammersmith & Charing Cross Hospitals, UK. Competing interests: organizes an annual multidisciplinary endocrine surgical symposium that is sponsored by pharmaceutical companies; none are related to thyroid disease. Also is paid a lecturing fee to teach thyroid surgical technique annually at the European Surgical Institute funded by Ethicon.
MEDICINE 37:8
Figure 1 A solitary nodule later found to be malignant on thyroid cytology.
436
Ó 2009 Elsevier Ltd. All rights reserved.
THYROID
Combined goitre classification Type of goitre
Example
Simple euthyroid Diffuse goitre goitre (sporadic/endemic) Multinodular goitre Toxic goitre Solitary toxic nodule Toxic multinodular (Plummer’s) Diffuse autoimmune (Graves’) Thyroiditis Subacute (de Quervain’s) Autoimmune (Hashimoto’s) Riedel’s Neoplasia Adenoma Carcinoma (primary/metastasis) Others Amyloidosis Chronic bacterial infection (TB/syphilis) Actinomycosis
Figure 2 A large multinodular goitre causing local compression.
enlargement does not allow the exclusion of malignancy on clinical grounds alone. The presence of local compressive symptoms (dysphagia and dyspnoea) should be enquired about specifically. Dysphonia in the presence of a goitre is suggestive of thyroid malignancy invading the recurrent laryngeal nerve and causing vocal cord paralysis. Local compressive-type symptoms disproportionate to the size of the goitre, especially if coinciding with pain, should alert to the possibility of thyroiditis. The presence of symptoms of hyperthyroidism e weight loss, tremor, anxiety, insomnia, etc. e is suggestive of toxicity and has been discussed above. Specific malignancy risk factors should be enquired about e a family history and a history of radiation exposure. Suspicion of medullary thyroid cancer requires a focused history regarding MEN2 syndrome (e.g. phaeochromocytoma and hyperparathyroidism).
Table 2
Examination Neck examination is conventionally performed from behind, with the patient seated. Any neck lump in the anterior triangle of the neck that rises and descends on swallowing is thyroidrelated. Once the clinical thyroid status has been established the neck lump is examined with a view to establishing its size, shape, margins, consistency, tenderness and mobility. It is also necessary to establish whether this is a solitary/dominant nodule or the smooth enlargement of the whole gland. Hard nodules with poorly defined margins raise suspicions of malignancy but Hashimoto’s thyroiditis may also be both firm and ill-defined. In all patients the presence or absence of cervical lymphadenopathy should be established.
Investigation of a goitre
Goitre classifications Criterion
Groups
Epidemiology
Endemic Sporadic Familial
Aetiology
Iodine deficiency Graves’ disease Hashimoto’s thyroiditis (in enlargement phase) Neoplasia Goitrogenous nutrients and drugs (thiocyanates, lithium) Dyshormonogenesis
Morphology Anatomy
Laboratory investigations The essential tests to be performed are the thyroid function tests: TSH, T3 and T4. In addition, a number of accessory tests can be performed. These are: thyroid autoantibody levels, if there is a suspicion of autoimmune thyroid disease or if a lymphoma is suspected (the latter occurs almost exclusively on a background of Hashimoto’s thyroiditis) calcitonin estimation, where medullary thyroid cancer is suspected. Fine-needle aspiration cytology Fine-needle aspiration cytology is the investigation of choice in solitary and dominant thyroid nodules. The procedure is performed by the clinician or under ultrasound guidance for small, less well-defined or awkwardly placed nodules.9 The investigation is well tolerated and provides excellent levels of preoperative diagnosis. Increasingly the Thy1e5 classification is adopted in the UK and forms the basis for treatment (Table 3).
Diffuse Multinodular Cervical Retrosternal
Functional status Euthyroid Toxic
Radiological investigations Radiological investigations are requested with a view to asking a specific question.
Table 1
MEDICINE 37:8
437
Ó 2009 Elsevier Ltd. All rights reserved.
THYROID
Thy1e5 classification of thyroid cytology Cytology
Description
Action
Thy1 Thy2 Thy3
Non-diagnostic smear Non-neoplastic/benign Follicular lesion/suspected follicular neoplasm
Thy4
Suspicious (but not absolutely diagnostic) of papillary, medullary or anaplastic carcinoma, or lymphoma) Diagnostic of malignancy (unequivocal features of papillary, medullary or anaplastic carcinoma, lymphoma or metastatic tumour)
FNA should be repeated Repeat to confirm diagnosis within 6 months Most of these patients should be treated by surgical removal of the lobe for diagnosis Surgical intervention is indicated or the aspirate should be repeated
Thy5
Surgical intervention is indicated for nearly all primary tumours except lymphoma and anaplastic cancer
FNA: fine-needle aspiration.
Table 3
Thyroid ultrasound scanning: ultrasound is rarely independently diagnostic but may be used to guide fine-needle aspiration cytology. Ultrasonographic criteria for thyroid malignancy may add weight to clinical and/or cytological findings. It is also excellent at assessing for the coexistence of cervical lymphadenopathy.
Thyroid malignancy Given the rarity of thyroid cancer it is best managed in a multidisciplinary team context in regional centres. Thyroid malignancies are classified according to the cell of origin:
CT and MRI scanning of goitres: cross-sectional imaging (magnetic resonance imaging (MRI) or computed tomography (CT)) is indicated when the extent of the goitre or tracheal compression are in doubt at clinical examination. Airway compression may be confirmed using the respiratory flowevolume loop.
Accounts for 85% of thyroid malignancy. All age groups, more common in women in young middle age. Tendency to be multifocal, can be locally invasive and spreads to regional lymph nodes even when the cancers are of small size.13
Thyrocytes Papillary thyroid cancer (PTC)
Treatment
Surgery is the primary mode of treatment e extent is dependent on the size of the primary tumour and the evidence of lymph node metastasis. There is a general trend towards a more comprehensive surgical approach, including lymphadenectomy of the central compartment of the neck in all but low-risk patients.14 Radioiodine therapy is recommended in all high-risk patients. Lifelong follow-up with TSH suppression to reduce the risk of recurrence.15 Prognosis: with the appropriate treatment most PTC patients do well with up to 10% dying of their disease.16
Radionuclide imaging: most thyroid malignancies do not concentrate radioisotopes (and thus appear ‘cold’), whereas hot nodules are associated with a low incidence of malignancy. However, less than 20% of cold nodules turn out to be cancers, the remaining 80% resulting from colloid nodules, haemorrhage, cysts or inflammatory lesions. Scintiscanning has therefore been abandoned in euthryoid patients and has been replaced by fine-needle cytology.10
Treatment of multinodular goitre and thyroid malignancy Multinodular goitres Euthyroid asymptomatic benign multinodular goitres do not require treatment unless there is a clinical suspicion or a history of childhood radiation exposure.11 Patients with local compressive symptoms are best served by surgery since the use of suppressive doses of thyroxine to halt or delay the goitre progress usually fails. Retrosternal goitres arguably require surgical intervention, based on the risk of acute or chronic airway obstruction, the malignancy risk in a place that is difficult to monitor and because direct questioning suggests that most patients are symptomatic. This surgical dogma, however, does not stand up to the rigour of an evidence-based analysis, so patients are best considered on a case-by-case basis.12 The threshold for surgery in younger patients with goitres is lower since these patients are more likely to become symptomatic.
MEDICINE 37:8
Follicular thyroid cancer (FTC)
10% of thyroid malignancy. Affects an older age group. Diagnosis requires histological analysis of capsular and vascular invasion so cytology identifies only potential follicular neoplasms. Haematogenous spread is preferred over lymphatic spread (<5%). Treatment
Thyroidectomy extent determined by tumour size and invasion. Radioiodine ablation and lifelong TSH suppression therapy with follow-up as for PTC is required. The less favourable prognosis of FTC is mainly related to the older age group affected.
438
Ó 2009 Elsevier Ltd. All rights reserved.
THYROID
Hurtle cell carcinoma
2 Gaitan E. Intervention policy in endemic goitre areas. Thyroid 1990; 2: 113. 3 Dumont JE, Ermans AM, Maenhaut C, Coppe´e F, Stanbury JB. Large goitre as a maladaptation to iodine deficiency. Clin Endocrinol (Oxf) 1995; 43: 1. 4 Kopp P, Kimura ET, Aeschimann S, et al. Polyclonal and monoclonal thyroid nodules co-exist within human multinodular goitres. J Clin Endocrinol Metab 1994; 79: 134. 5 Kebebew E. Hereditary non-medullary thyroid cancer. World J Surg 2008; 32: 678e82. 6 Nakachi K, Hayashi T, Hamatani K, Eguchi H, Kusunoki Y. Sixty years of follow-up of Hiroshima and Nagasaki survivors: current progress in molecular epidemiology studies. Mutat Res 2008; 659: 109e17. 7 Hatch M, Brenner A, Bogdanova T, et al. A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to Iodine-131 from Chernobyl fallout. In utero exposure to Iodine-131 from Chernobyl. J Clin Endocrinol Metab 2009; 94: 899e906. 8 Gough J, Scott-Coombes D, Palazzo FF. Thyroid incidentaloma: an evidence-based assessment of management strategy. World J Surg 2008; 32: 1264e8. 9 Danese D, Sciacchitano S, Farsetti A, Andreoli M, Pontecorvi A. Diagnostic accuracy of conventional versus sonography-guided fineneedle aspiration biopsy of thyroid nodules. Thyroid 1998; 8: 15e21. 10 Giuffrida D, Gharib H. Controversies in the management of cold, hot and occult thyroid nodules. Am J Med 1995; 99: 642e50. 11 Levy EG, Greenlee C, Mandel S, Kaplan M. Should you always trust FNA interpretations? Thyroid 2000; 10: 279. 12 White ML, Doherty GM, Gauger PG. Evidence-based surgical management od substernal goiter. World J Surg 2008; 32: 1285e300. 13 Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003; 13: 381e7. 14 Palazzo FF, Gosnell J, Savio R, et al. Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades. Eur J Surg Oncol 2006; 32: 340e4. 15 British Thyroid Association. BTA Guidelines for the management of thyroid cancer, 2nd edn, 2008. Also available from: http://www. british-thyroid-association.org (accessed 22.05.09). 16 Hay ID, Klee GG. Thyroid cancer diagnosis and management. Clin Lab Med 1993; 13: 725.
Uncommon. Tendency to more aggressive behaviour. Treatment
Similar to an aggressive PTC. Total thyroidectomy and central compartment lymphadenectomy. Radioiodine therapy less likely to be effective due to the lower uptake in these tumours. Anaplastic carcinomas
Uncommon dedifferentiated devastatingly aggressive variant of PTC. Affects patients in their sixth decade onwards: history of dramatic increase in goitre size. Few survive more than 3 months. Best results are achieved using a combination of surgery, external irradiation and chemotherapy. Parafollicular C cells Medullary thyroid cancer (MTC)
Sporadic or part of MEN2 syndrome. Spreads via lymphatics. Treatment
Comprehensive thyroid and lymph node surgery. Radioiodine not taken up. Thyroidal lymphocytes
Lymphoma: uncommon and occurs almost exclusively in patients with a history of autoimmune thyroiditis. The treatment is chemo-radiotherapy, which can be curative in localized disease. Metastases (rare)
Renal, breast, uterine and melanoma.
A
REFERENCES 1 Reiners C, Wegscheider K, Schicha H, et al. Prevalence of thyroid disorders in the working population of Germany: ultrasonography screening in 96,278 unselected employees. Thyroid 2004; 14: 926e32.
MEDICINE 37:8
439
Ó 2009 Elsevier Ltd. All rights reserved.