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Multiple endocrine neoplasia type 1

ORPHA652
Synonym(s) MEN 1
Wermer syndrome
Prevalence 1-9 / 100 000
Inheritance Autosomal dominant
or Not applicable
Age of onset All ages
ICD-10
  • D44.8
OMIM
UMLS
  • C0025267
MeSH
  • D018761
MedDRA
  • 10028190

Summary

Multiple endocrine neoplasia Type 1 (MEN1) is a frequent form of MEN (see this term), a rare inherited cancer syndrome, characterized by the development of neuroendocrine tumors of the parathyroid, pancreas, and anterior pituitary gland, and less commonly the adrenal cortical gland, with other non-endocrine tumors in some patients.

Estimated prevalence ranges from 1/10,000 to 1/30,000. The sex ratio in MEN1 appears to be equal.

In individuals with MEN1, tumors can develop at any age. 95% of patients develop clinical symptoms by the 5th decade. Parathyroid tumors causing hyperparathyroidism are the most common (95% of patients), followed by pancreatic islet tumors (40%) and anterior pituitary tumors (30%). Pancreatic neuroendocrine tumors include Zollinger-Ellison syndrome (50%), insulinoma (33%), glucagonoma (5%), vasoactive intestinal peptide (VIP)-oma, pancreatic polypeptide (PP)-oma, and are associated with high levels of morbidity and mortality (see these terms). Tumors of the pituitary include prolactinoma (66%), somatotrophinoma (25%), and about 5% each for ACTHomas and non-functioning adenomas. The most common initial manifestation is primary hyperparathyroidism (from 20 years). Other signs include those of hypercalcemia, hypophosphatemia and elevated parathyroidhormone (PTH) levels (often asymptomatic). Overt clinical signs may include nephrolithiasis, peptic ulcer, polyuria, polydipsia, constipation, fatigue, depression, confusion, and anorexia. Pituitary tumors may cause oligomenorrhea/amenorrhea and galactorrhea in females and sexual dysfunction in males. Non-endocrine tumors found in patients with MEN1 include angiofibroma (88%), collagenoma (72%), adrenocortical tumor (35%), lipoma (33%), carcinoid tumor and carcinoid syndrome (10%), meningioma (less than 10%), facial ependymoma (less than 5%) (see these terms), and leiomyoma.

MEN1 is caused by inactivating mutations in the MEN1 gene (11q13) encoding the menin protein, a tumor suppressor. Loss of functional menin is related to unregulated cell division, causing tumor development. In certain patients (<2%) who present a phenotype very similar to MEN1, mutations in the cyclin-dependent kinase inhibitor genes have been demonstrated: CDKN1A (6p21.1), CDKN2B (9p21), and CDKN2C (1p32.3).

The diagnosis is based on standard approaches for each of the specific tumors, as followed in non-MEN patients. MEN1 is diagnosed when there are two endocrine tumors (parathyroid, pituitary, and/or pancreatic). Biochemical and genetic testing are used to confirm the diagnosis of MEN1.

The differential diagnosis includes other types of MEN, specifically MEN2A and MEN4 (see these terms). Primary hyperparathyroidism should also be considered.

Prenatal diagnosis for pregnancies at increased risk is possible.

MEN1 displays a high degree of penetrance. Most cases are the result of autosomal dominant inheritance (>90%). Some cases of de novo occurrence are however reported. Genetic counseling should be provided to affected individuals and their families.

Annual life-long screening is recommended for individuals from affected families. 6-monthly screening is recommended for affected patients (CT, MRI, blood biochemistry). Treatment is based on approaches for each specific tumor. For example, hyperparathyroidism can be treated with subtotal or total parathyroidectomy and prolactinomas with dopamine agonists. Surgery may be indicated for insulinomas and other pancreatic tumors.

Malignancy is the main risk in MEN1 patients (accounting for approximately 30% of deaths). Early diagnosis and treatment success are the main prognostic factors.

Expert reviewer(s)

  • Pr Maria Luisa BRANDI

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Detailed information

Summary information
Review article
  • EN (2006)
Article for general public
Clinical genetics review
  • EN (2015)
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