Multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type I1 (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, islet cells of the pancreas and parathyroid glands. 

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

Epidemiology

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)
• carcinoid tumours
• hepatic focal nodular hyperplasia ⁵
• breast carcinoma ⁸
• meningiomas ⁸

Clinical presentation

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

MEN type I1 is an autosomal dominant syndrome characterized by ^1-7:

• pituitary adenomas
  • prolactinoma (most common)
  • 30% of patients
• islet cell tumours of the pancreas
  • gastrinoma (most common) followed by glucagonoma
  • 50-80% of patients
  • a significant cause of mortality
• parathyroid proliferative parathyroid gland lesions diseases⁷
  • parathyroid hyperplasia (most common)
    • hyperparathyroidism is seen in 80-95% of patients
  • parathyroid adenoma
  • parathyroid carcinoma (rare)

Handy mnemonics for recalling MEN type I1: 

• PPP or PiParPanc

Pathology

Genetics

The abnormality is related to MEN1, a tumour 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 MEN type I1. 

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