Diagnosis and treatment of multiple endocrine neoplasia type 1 (MEN1)

Minerva Endocrinol. 2013 Mar;38(1):17-28.

Abstract

Multiple endocrine neoplasia type 1 (MEN1; formerly known as Wermer syndrome) is a rare disorder characterized by the combined occurrence of two or more tumors involving parathyroid, pancreatic islets and anterior pituitary glands; some other tumors have also been described. In most cases it is inherited in an autosomic dominant manner but it may occur sporadically. The MEN1 gene (MEN1) is located on chromosome 11q13, it is composed of ten exons that encode a 610 amino acid protein called menin. Menin, with no homology to any other known protein, interacts with several different proteins and plays an important role in regulation of cell growth, cell cycle, genome stability and synapse plasticity. Familiar MEN1 has a high degree of penetrance with clinical or biochemical manifestations of the disease in 80% and 98%, respectively, by the fifth decade. Clinical manifestations are related to tumor localizations and their secretory products. Hyperparathyroidism is the most common feature of MEN1 (95% of patients), pancreatic islet tumors or pancreatic NET (neuroendocrine tumor) occur in 40-70% and pituitary tumors in 30-40% of MEN 1 patients. In addition, other tumors, such as adrenal cortical tumors, carcinoid tumors, lipomas, angiofibromas, colagenomas and meningiomas may be present. Occurrence of de novo mutations appear in 10% of all patients with MEN1. A correlation between genotype and phenotype has not been found and, even more, combinations of these tumors may be different in members of the same family. Untreated patients have a decreased life expectancy, with a 50% probability of death by the age of 50 years and the cause of death is mostly directly related to MEN1, being the most important causes malignant pancreatic neuroendocrine tumors (NET) and thymic carcinoids. Treatment for each type of endocrine tumor is generally similar as in non-MEN1 associated tumors, but results are less successful according to multiplicity of tumors, higher metastatic disease, larger and more aggressive tumors and more resistant to treatment. The prognosis might improve by preclinical tumor diagnosis and appropriated treatment.

Publication types

  • Review

MeSH terms

  • Biomarkers / metabolism
  • Early Diagnosis
  • Exons
  • Genotype
  • Humans
  • Multiple Endocrine Neoplasia Type 1 / diagnosis*
  • Multiple Endocrine Neoplasia Type 1 / epidemiology
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Multiple Endocrine Neoplasia Type 1 / therapy
  • Mutation
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / therapy
  • Parathyroid Neoplasms / diagnosis*
  • Parathyroid Neoplasms / epidemiology
  • Parathyroid Neoplasms / genetics
  • Parathyroid Neoplasms / therapy
  • Phenotype
  • Pituitary Neoplasms / diagnosis*
  • Pituitary Neoplasms / epidemiology
  • Pituitary Neoplasms / genetics
  • Pituitary Neoplasms / therapy
  • Prevalence
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Spain / epidemiology

Substances

  • Biomarkers
  • MEN1 protein, human
  • Proto-Oncogene Proteins