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  • Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with endocrine tumors of the parathyroids, the enteropancreatic neuroendocrine tissues, the anterior pituitary, and foregut carcinoid. Associated nonendocrine tumors include facial angiofibromas, skin collagenomas, and lipomas.

  • Most of the tumors are benign and produce symptoms and signs by oversecreting hormones (parathyroid hormone, gastrin, prolactin, etc.). Associated gastrinomas and foregut carcinoid tumors have a substantial malignant potential.

  • The most common endocrinopathy is primary hyperparathyroidism with several features different from features in sporadic parathyroid adenoma. Hyperparathyroidism in MEN1 is expressed earlier than in sporadic adenoma; 50 percent of gene carriers express it by ages 18 to 30. Most MEN1 patients have multiple parathyroid tumors and, after successful subtotal parathyroidectomy, have a high likelihood of late recurrence. Hyperparathyroidism can exacerbate the simultaneous Zollinger-Ellison syndrome in MEN1.

  • The MEN1 gene was identified by positional cloning in 1997. Its sequence predicted a novel protein termed menin.

  • MEN1 germ-line mutations have been found in over 80 percent of MEN1 families and in a similar fraction of patients with sporadic MEN1. Clinical use of germ-line MEN1 mutation testing can give valuable information. It does not have the urgency of germ-line RET mutation testing for MEN2a or MEN2b.

  • Certain sporadic endocrine and nonendocrine tumors often show somatic MEN1 mutation. In fact, MEN1 is the known gene most commonly mutated in sporadic parathyroid adenoma, gastrinoma, insulinoma, and bronchial carcinoid tumor.

  • MEN1 is likely a tumor-suppressor gene, since most MEN1 tumors and many sporadic endocrine tumors with MEN1 mutation show inactivation (recognized as loss of heterozygosity) of the normal allele at 11q13, the MEN1 locus.

  • The MEN1-encoded protein, menin, is mainly located in the nucleus. It binds to and inhibits junD, an AP1 transcription factor. It shows no protein homologies. Most germ-line or somatic MEN1 mutations predict truncation of the menin protein and are thus likely to cause inactivation of menin function. Inactivation-type mutation further supports menin's predicted role as a tumor suppressor.


Multiple endocrine neoplasia is a broad term that encompasses many distinct disorders. Literally interpreted, it includes all patients and families with endocrine neoplasia in more than one tissue type. Thus it includes patients with two coincidental endocrine neoplasms such as parathyroid adenoma and pituitary microadenoma, and it can include patients with a neoplasm that stimulates another tumor, such as pancreatic islet tumor secreting growth hormone-releasing hormone, which causes pituitary hyperplasia.

Within this broad definition, multiple endocrine neoplasia type 1 (MEN1) and multiple endocrine neoplasia type 2 (MEN2) stand out as occurring repeatedly in sporadic cases and also within families. The main endocrine expressions of MEN1 are parathyroid tumor, enteropancreatic neuroendocrine tumor, anterior pituitary tumor, and foregut carcinoid tumor. Nonendocrine expressions include lipoma, facial angiofibroma, and skin collagenoma (Table 57–1).

Table 57–1:Summary Features of Multiple Endocrine Neoplasia Type 1 with Estimated Average Penetrance ...

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