Multiple Endocrine Neoplasia Type 1

Updated: Dec 11, 2015
  • Author: Thomas N Darling, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial tumor syndrome (also termed Wermer syndrome) in which persons develop tumors of the parathyroid glands, the enteropancreatic neuroendocrine system, the anterior pituitary gland, and the skin. The most common endocrine tumors are parathyroid tumors that cause hyperparathyroidism and hypercalcemia. Other tumors include gastrinomas, insulinomas, prolactinomas, and carcinoid tumors. [1, 2]

Cutaneous tumors are common in MEN1, but they can be easily overlooked because of their subtle appearance. The cutaneous tumors include multiple angiofibromas (previously considered pathognomonic for tuberous sclerosis), collagenomas, and lipomas. [3, 4] Angiofibromas and collagenomas are markers for this tumor syndrome. In the evaluation of a cohort of patients with Zollinger-Ellison syndrome due to gastrinomas, for example, the dermatological criterion of more than 3 angiofibromas or 1 or more collagenomas was sensitive (75%) and specific (95%) for the diagnosis of MEN1. [5]

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Pathophysiology

Patients with MEN1 inherit a mutation in a tumor suppressor gene called MEN1 on chromosome band 11q13. This gene encodes a 610-amino acid protein, menin, that regulates transcription, proliferation, and genome stability. Menin appears to be located mostly in the nucleus, where it has multiple binding partners, including junD and histone modifiers. [6, 7, 8, 9] A mutant menin has been shown to be defective for the transforming growth factor-beta signaling pathway. [10]

Tumor formation involves inactivating mutations of both alleles of the MEN1 gene. In people without MEN1 , two independent somatic mutations must occur within a single cell for tumor formation. In an individual with MEN1 , the first mutation is already present in all of the patient's cells, so that only a single somatic mutation is required. This accounts for the multiple tumors and the tumors occurring at an earlier age. Second-hit mutations in MEN1 have been documented in angiofibromas, collagenomas, and lipomas in patients with MEN1. [11, 12, 13]

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Epidemiology

Frequency

International

The frequency of multiple endocrine neoplasia type 1 (MEN1) is estimated to be 1 case in 30,000 persons. [14]

Mortality/Morbidity

Benign endocrine and cutaneous tumors cause morbidity, and malignancies cause most mortality (see Complications) in multiple endocrine neoplasia type 1 (MEN1).

Race

No racial predilection is known for multiple endocrine neoplasia type 1 (MEN1).

Sex

The incidence of multiple endocrine neoplasia type 1 (MEN1) is equal for men and women. The frequencies of most tumors are similar in men and women, except bronchial carcinoids are more common in women and thymic carcinoids are more common in men. [1, 15, 16]

Age

Endocrine tumors in MEN1

The age of onset of endocrine tumors is usually in the teenaged years; however, symptoms from these tumors may not appear for several years, and the diagnosis is frequently delayed until the fourth decade of life.

Cutaneous tumors in MEN1

Cutaneous tumors may develop prior to the manifestation of overt clinical symptoms resulting from endocrine tumors. The earliest cutaneous tumors appear in the teenaged years. The recognition of these cutaneous tumors has been used in the presymptomatic diagnosis of patients with MEN1. [17, 18]

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