Multiple endocrine neoplasia

Multiple endocrine neoplasia (MEN) is a group of inherited disorders characterized by the development of tumors in two or more endocrine glands. These syndromes primarily affect hormone-producing glands such as the parathyroid glands, pituitary gland, pancreas, thyroid (particularly the C-cells), and adrenal glands. The major subtypes include MEN type 1 (MEN1, also called Wermer syndrome), MEN type 2A (MEN2A, also called Sipple syndrome), MEN type 2B (MEN2B, also called MEN3), and MEN type 4 (MEN4). Each subtype has a distinct genetic basis and clinical presentation, though all share the hallmark of multiple endocrine tumors occurring in the same individual or family. MEN1 is caused by pathogenic variants in the MEN1 gene and is characterized by tumors of the parathyroid glands (causing primary hyperparathyroidism), anterior pituitary gland, and pancreatic islet cells (gastrinomas, insulinomas). MEN2A and MEN2B are caused by pathogenic variants in the RET proto-oncogene. MEN2A features medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism, while MEN2B includes medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and a marfanoid body habitus. MEN4, caused by variants in the CDKN1B gene, presents similarly to MEN1 but is much rarer. Symptoms vary depending on which glands are affected and may include hypercalcemia, peptic ulcers, hypoglycemia, headaches, visual disturbances, hypertension, diarrhea, and palpitations. Treatment is tailored to each tumor type and may include surgical removal of affected glands, medical management of hormone excess, and lifelong surveillance. For MEN2, prophylactic thyroidectomy is recommended based on the specific RET mutation and associated risk level. Genetic testing and early screening of at-risk family members are critical components of management, enabling early detection and intervention to reduce morbidity and mortality.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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