Multiple endocrine neoplasia

Last updated: June 14, 2023

Summary

Multiple endocrine neoplasia (MEN) is a term used to describe three autosomal dominant syndromes that are associated with certain hormone-producing neoplasias. There are three subtypes: MEN 1, MEN 2A, and MEN 2B. MEN 1 is caused by an altered menin protein expression and presents with primary hyperparathyroidism, often in association with endocrine pancreatic tumors and/or pituitary adenomas. MEN 2A and MEN 2B are caused by a mutated RET proto-oncogene and both present with medullary thyroid carcinoma and sometimes pheochromocytoma. MEN 2A is further associated with primary hyperparathyroidism as well, while MEN 2B causes a marfanoid habitus and sometimes neurinomas. If any of the individual conditions associated with MEN are suspected, especially in patients with a positive family history, it is important to consider a diagnostic workup for any of the other associations. Specific diagnostic and management approaches can be found within the articles for each of the individual conditions. Family members of MEN patients should receive genetic counseling. Those positive for mutated genes should be closely monitored and should undergo a total thyroidectomy if positive for the RET proto-oncogene.

Overview of multiple endocrine neoplasia
Feature	MEN 1 (formerly known as Wermer syndrome)	MEN 2
Feature	MEN 1 (formerly known as Wermer syndrome)	MEN 2A (formerly known as Sipple syndrome)	MEN 2B
Genetics	Mutation of the MEN1 gene (located on chromosome 11) → altered expression of menin protein	Altered expression of the RET proto-oncogene → elevated tyrosine kinase activity
Inheritance	Autosomal dominant
Prinicipal manifestations	Primary hyperparathyroidism (parathyroid adenoma)	Medullary thyroid carcinoma
Further manifestations	Endocrine pancreatic tumors Gastrinoma (most common) Insulinoma VIPoma Glucagonoma (rare) Pituitary adenoma: most commonly prolactinoma Carcinoid tumors (∼ 10–15% of cases) Nonendocrine tumors (e.g. angiofibromas, collagenomas, meningiomas)	Pheochromocytoma (∼ 40% of cases) ^[1]
Further manifestations		Primary hyperparathyroidism (∼ 20–30% of cases)^[2]	Multiple neurinomas: mucosal neuromas (e.g., lips, tongue), intestinal ganglioneuromatosis ) ^[3] Marfanoid habitus
Management	Parathyroidectomy Excision of pancreatic tumor Transsphenoidal surgery for excision of pituitary adenoma	Thyroidectomy including cervical lymph nodes Pheochromocytoma should first be ruled out (e.g., by measuring urine metanephrines) or treated before undergoing surgery If pheochromocytoma: adrenalectomy If hyperparathyroidism: parathyroidectomy

MEN 1: 3 "P"s = Parathyroid, Pancreas, Pituitary gland

MEN 2A: 1 "M", 2 "P”s = Medullary thyroid carcinoma, Pheochromocytoma, Parathyroid

MEN 2B: 2 “M”s, 1 “P” = Medullary thyroid carcinoma, Marfanoid habitus/Multiple neuromas, Pheochromocytoma

Remembering that the inheritance pattern of MEN syndromes is autosomal dominant requires MENtal dominance.

MEN (multiple endocrine neoplasia) syndromes Mucosal neuroma

References:^[1]^[2]^[3]^[4]

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