Medullary thyroid carcinoma: biology, inherited syndromes and surveillance
THE CONTEXT
Medullary carcinoma arises from neural crest-derived parafollicular C cells and may occur sporadically or as familial disease.
Tumour products and clinical features
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The tumours resemble carcinoid tumours and produce high serum levels of calcitonin and carcinoembryonic antigen.
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Calcitonin falls after resection and rises with recurrence, making it a valuable follow-up tumour marker.
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Diarrhoea occurs in 30% of cases and may result from tumour production of 5-hydroxytryptamine or prostaglandins.
Familial disease and endocrine syndromes
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Multiple endocrine neoplasia type 2A combines medullary carcinoma with adrenal phaeochromocytoma and hyperparathyroidism, usually caused by hyperplasia.
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Familial disease frequently affects children and young adults. Sporadic disease can occur at any age and has no sex predominance.
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Familial medullary carcinoma with prominent mucosal neuromas of the lips, tongue and inner eyelids, together with a Marfanoid habitus, is termed multiple endocrine neoplasia type 2B.
Spread and prognosis
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Lymph node involvement occurs in 55–60% of cases, and blood-borne metastases are common.
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The tumours are not TSH dependent and do not take up radioactive iodine.
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Prognosis depends on the stage at diagnosis. Nodal involvement virtually eliminates the prospect of cure.
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Even small tumours confined to the thyroid may already have spread, particularly in familial disease.
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Disease progression can be slow, with an indolent course and long survival even without cure.
Screening relatives and preventive surgery
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Relatives in familial cases should be offered genetic screening, with results guiding recommendations for prophylactic thyroidectomy.
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Some relatives may be monitored into adulthood using serial calcitonin measurements.
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The highest-risk mutations are associated with early-onset disease, for which total thyroidectomy is recommended during infancy.