Dermatologic Manifestations of Multiple Endocrine Neoplasia Type 1 (MEN1)

Updated: Sep 21, 2022
  • Author: Thomas N Darling, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Practice Essentials

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial tumor syndrome (also termed Wermer syndrome) characterized by 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] Other dermatologic findings are café au lait macules, confetti-like hypopigmented macules, and multiple gingival papules. [3]

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]

For patient education resources related to multiple endocrine neoplasia type 1 (MEN1), see the Symptoms of Multiple Endocrine Neoplasia, as well as Anatomy of the Endocrine System.



Patients with MEN1 inherit a mutation in a tumor suppressor gene called MEN1 on chromosome band 11q13. [6, 7] 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. [8, 9, 10] A mutant menin has been shown to be defective for the transforming growth factor-beta signaling pathway. [11]

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. [12, 13, 14]




Worldwide, the frequency of MEN1 is estimated to be 1 case in 30,000 persons. [15]

Race- and sex-related demographics

No racial predilection is known for MEN1. Incidence rates of MEN1 are equal for men and women, and the frequencies of most tumors are similar in men and women, except that bronchial carcinoids are more common in women and thymic carcinoids are more common in men. [1, 16, 17]


The age of onset of endocrine tumors is usually in the teenage 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 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. [18, 19]



In MEN1, benign endocrine and cutaneous tumors cause morbidity, and malignancies cause most mortality, with 70% of deaths caused by duodenopancreatic neuroendocrine tumors and thymic carcinoids.  Women have lower mortality rates than men, likely due to the higher incidence of thymic tumors. [20]

Endocrine tumors may hypersecrete hormone, causing hypercalcemia and recurrent nephrolithiasis (hyperparathyroidism), Zollinger-Ellison syndrome (hypergastrinemia), hypoglycemia (hyperinsulinemia), amenorrhea (hyperprolactinemia), or acromegaly (excess growth hormone).

Tumors of the pituitary gland may cause symptoms by mass effects. Pancreatic endocrine tumors, particularly gastrinomas, become malignant in about 50% of patients with MEN1. Untreated, patients may die from peptic ulcer disease, metastatic endocrine pancreatic carcinoma, or foregut carcinoid malignancy.

Angiofibromas, collagenomas, and lipomas do not typically cause symptoms, and they are mostly of cosmetic concern.