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medullary carcinoma of thyroid

A neuroendocrine tumour that comprises ±5% of thyroid cancers, arising in the C (parafollicular) cells of the ultimobranchial cleft—i.e., neural crest origin. It is either sporadic (70–90% of cases) or inherited (10–30%) as part of the autosomal dominant multiple endocrine neoplasia (MEN) types 2A or 2B, the latter in association with mutations of the RET proto-oncogene. The average age at diagnosis is 50; it is slightly more common in women.

Clinical findings
Related to local growth and compromised of regional structures; increased calcitonin causes hypercalcaemia, hypertension, paraneoplastic syndromes (e.g., Cushing syndrome) and neuromas.

Clinical forms
• Sporadic—70–90% of cases, mean age of onset 45; presenting as a solitary “cold nodule” (by thyroid scan), which may be accompanied by intractable diarrhoea and Cushing’s syndrome. 
• Familial—10–30% of cases, mean age of onset 35; multifocal and bilateral, accompanied by C-cell hyperplasia of residual thyroid tissue; familial MCT is often autosomal dominant and associated with multiple endocrine adenomatosis, usually type II (which has a germline abnormality on chromosome 10, an earlier age of onset and is often bilateral) or occasionally type III (IIb; less common, but more aggressive and rarely a non-aggressive form of MCT that is not associated with other neural or endocrine lesion).

MCTs may produce ACTH-like substance, biogenic amines, CEA, corticotropin-releasing factor, NGF, prolactin-releasing hormone, prostaglandins, melanin-stimulating hormone, histaminase, beta-endorphin, 5-hydroxytryptamine, serotonin, somatostatin, thyroglobulin.

Thyroid function tests
Usually normal.

Risk factors
Family history of multiple endocrine neoplasia MEN 2A or 2B, history of phaeochromocytoma, mucosal neuromas, hyperparathyroidism; RT to head or neck, the risk of radiation-induced thyroid nodularity and carcinoma increases with radiation dose and decreases the older the person was at the time of irradiation.
Metastases to
Cervical lymph nodes, mediastinum, lungs, liver, bone, brain, adrenal glands.

Total thyroidectomy, radioiodine.
70–80% 5-year survival; sporadic MCT has a 50% 10-year survival; 10- and 20-year survival is 63% and 44% respectively (papillary thyroid carcinoma has 95% 10-year survival). 70% develop nodal metastasis.

Medullary thyroid cancer (MTC)

A slow-growing tumor associated with MEN.
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