Authors' recommendations: Multiple endocrine neoplasia type 2 (MEN2), which has an estimated prevalence of 2.5 per 100,000 in the general population, is characterized by tumors of the thyroid, parathyroid, and adrenal glands. MEN2 is an autosomal dominant condition that results from variants in the rearranged during transfection (RET) proto-oncogene. Gain-of-function variants in RET, which is located on chromosome 10 at band q11.2, result in an overly active receptor tyrosine kinase that functions in the development of neural crest-derived cells, including parafollicular C-cells in the thyroid gland, parathyroid cells, and chromaffin cells in the adrenal gland. There are three clinical subtypes of MEN2: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). All three types of MEN2 are associated with a 95% to 100% chance of developing medullary thyroid carcinoma (MTC), a calcitonin-secreting tumor of the parafollicular C-cells. MEN2A, which accounts for 70% to 80% of MEN2 cases, is also associated with a significant risk of pheochromocytoma (a typically benign tumor of the adrenal gland that causes overproduction of epinephrine and related hormones) and hyperplasia or adenomas of the parathyroid glands leading to hyperparathyroidism. MEN2B accounts for approximately 5% of MEN2 cases and is characterized by the early development of an aggressive MTC (sometimes as early as infancy) and at least a 50% chance of developing a pheochromocytoma. Hyperparathyroidism is not seen in MEN2B patients. Additional features that are specific to MEN2B include mucosal neuromas of the lips and tongue, intestinal ganglioneuromatosis, corneal thickening, and a marfanoid habitus. FMTC accounts for 10% to 20% of MEN2 cases and is considered the mildest type of MEN2. By definition, FMTC is characterized by familial MTC in the absence of pheochromocytoma, hyperparathyroidism, and other related medical conditions. The management of MEN2 depends on the subtype but typically includes prophylactic thyroidectomy in asymptomatic RET carriers, therapeutic thyroidectomy in patients with MTC, monitoring for pheochromocytoma and hyperparathyroidism, and treatment of these conditions when diagnosed. Significant genotype-phenotype correlations have been established in MEN2 patients, which has allowed for genotype-based recommendations regarding the timing of prophylactic thyroidectomy in carriers of common RET gene variants.

Project Status: Completed

Year Published: 2012

URL for published report: The report may be purchased from:http://www.hayesinc.com/hayes/crd/?crd=14138

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

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Contact Email: saleinfo@hayesinc.com

Copyright: 2012 Winifred S. Hayes, Inc