Multiple endocrine neoplasia type 1 (MEN1), also known as Wermer syndrome, is an autosomal dominant genetic disease that results in proliferative lesions in multiple endocrine organs, particularly the pituitary gland, pancreas, and parathyroid glands. 

There are other multiple endocrine neoplasia syndromes and these are discussed separately. 

Epidemiology

MEN1 has an estimated prevalence of 2 per 100,000, and there is no gender predilection ¹⁰.

Associations

In addition to the characteristic lesions involving the pituitary, parathyroid, and pancreas, numerous other lesions are encountered with greater frequency in patients with MEN1. These include: 

• lipomas

• angiofibromas

• adrenal cortical lesions

  • adrenal adenomas

  • adrenocortical hyperplasia

  • cortisol-secreting adenomas

  • adrenal carcinomas (rare)

• neuroendocrine tumors

• hepatic focal nodular hyperplasia ⁵

• breast carcinoma ⁸

• meningiomas ⁸

Clinical presentation

Primary hyperparathyroidism is the commonest presentation, followed by pancreatic neuroendocrine tumors with associated hypersecretion syndromes; gastrinomas are most common and associated with Zollinger-Ellison syndrome ⁷. 

MEN1 is an autosomal dominant syndrome characterized by ^1-7:

• pituitary adenomas

  • prolactinoma (most common)

  • 30% of patients

• pancreatic neuroendocrine tumors

  • gastrinoma (most common: >50%), followed by insulinoma (4-6%), and glucagonoma (<3%) ⁹

  • 50-80% of patients

  • significant cause of mortality

• parathyroid proliferative diseases ⁷

  • parathyroid hyperplasia (most common)

    • hyperparathyroidism (80-95%)

  • parathyroid adenoma

  • parathyroid carcinoma (rare)

Handy mnemonics for recalling MEN1: 

• PPP or PiParPanc

Pathology

Genetics

The abnormality is related to MEN1, a tumor suppressor gene located on chromosome 11q13 which produces menin, a nuclear protein important for the regulation of gene expression. 

Treatment and prognosis

Treatment is directed to each individual manifestation. These are therefore discussed separately.

Pancreatic malignancy is the leading cause of mortality in MEN1. 

History and etymology

Harvey Cushing was the first to publish a case of MEN1 with the classical triad in 1927. MEN1 was first characterized as a discrete pathological entity by an American-Austrian physician Paul Wermer et al., whilst working at Presbyterian Hospital, as part of a Columbia University team in New York, USA in 1954 ^3,8. The MEN1 gene was discovered in 1997 ⁸.

See also

• MEN1 (Wermer syndrome)

• MEN2

  • MEN2a (Sipple syndrome)

  • MEN2b (mucosal neuroma syndrome)

  • familial medullary thyroid carcinoma

• MEN4

• Carney complex