Multiple endocrine neoplasia type 2

Multiple endocrine neoplasia type 2 (also known as 'Pheochromocytoma and amyloid producing medullary thyroid carcinoma', 'PTC syndrome,' and 'Sipple syndrome') is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs (e.g. thyroid, parathyroid, and adrenals), but may also occur in endocrine tissues of organs not classically thought of as endocrine. Multiple endocrine neoplasia type 2 (also known as 'Pheochromocytoma and amyloid producing medullary thyroid carcinoma', 'PTC syndrome,' and 'Sipple syndrome') is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs (e.g. thyroid, parathyroid, and adrenals), but may also occur in endocrine tissues of organs not classically thought of as endocrine. MEN2 is a sub-type of MEN (multiple endocrine neoplasia) and itself has sub-types, as discussed below. MEN2 can present with a sign or symptom related to a tumor or, in the case of multiple endocrine neoplasia type 2b, with characteristic musculoskeletal and/or lip and/or gastrointestinal findings. Medullary thyroid carcinoma (MTC) represents the most frequent initial diagnosis. Occasionally pheochromocytoma or primary hyperparathyroidism may be the initial diagnosis. Pheochromocytoma occurs in 33-50% of MEN2 cases. In MEN2A, primary hyperparathyroidism occurs in 10–50% of cases and is usually diagnosed after the third decade of life. Rarely, it may present in childhood or be the sole clinical manifestation of this syndrome. MEN2A associates medullary thyroid carcinoma with pheochromocytoma in about 20–50% of cases and with primary hyperparathyroidism in 5–20% of cases. MEN2B associates medullary thyroid carcinoma with pheochromocytoma in 50% of cases, with marfanoid habitus and with mucosal and digestive neurofibromatosis. In familial isolated medullary thyroid carcinoma the other components of the disease are absent.In a review of 85 patients 70 had MEN2A and 15 had MEN2B. The initial manifestation of MEN2 was medullary thyroid carcinoma in 60% of patients, medullary thyroid carcinoma synchronous with pheochromocytoma in 34% and pheochromocytoma alone in 6%. 72% had bilateral pheochromocytomas. The table in the multiple endocrine neoplasia article lists the genes involved in the various MEN syndromes. Most cases of MEN2 derive from a variation in the RET proto-oncogene, and are specific for cells of neural crest origin. A database of MEN-implicated RET mutations is maintained by the University of Utah Department of Physiology. The protein produced by the RET gene plays an important role in the TGF-beta (transforming growth factor beta) signaling system. Because the TGF-beta system operates in nervous tissues throughout the body, variations in the RET gene can have effects in nervous tissues throughout the body. MEN2 generally results from a gain-of-function variant of a RET gene. Other diseases, such as Hirschsprung disease, result from loss-of-function variants. OMIM #164761 lists the syndromes associated with the RET gene.