Multiple endocrine neoplasia type 4 (MEN4, OMIM #610755) is a genetic disease caused by mutations in the CDKN1B gene. It leads to a predisposition to parathyroid adenomas with primary hyperparathyroidism (PHPT) and tumors of adenohypophysis (anterior pituitary neuroendocrine tumors, PitNET) and is therefore similar to the clinical presentation of MEN1. In addition, renal angiomyolipomas, neuroendocrine tumors of the gastroenteropancreatic tract, and tumors of the uterus, adrenal glands, and thyroid may occur as well.

Key Data

< swipe to see entire table >
Synonym CDKN1B-related MEN
Gene product p27kip1
Function The cyclin-dependent kinase inhibitor 1B plays an important role in blocking the cell cycle.
Heredity Autosomal dominant
Prevalence Very rare, exact numbers unknown
Genotype-phenotype correlation 13 different mutations have been found to date; a clear genotype-phenotype correlation is not yet known.
Penetrance 100% for PHPT
< swipe to see entire table >


Genetic Diagnostics

The genetic diagnostics for a mutation of the CDKN1B gene is indicated in all people with PHPT in whom no MEN1 mutation has been identified.

Differential Diagnoses

Clinical Presentation

The clinical presentation of MEN4 is similar to that of MEN1. Primarily occurring are parathyroid adenomas with PHPT and neuroendocrine tumors of adenohypophysis (PitNET), which may be somatotrophic, corticotrophic, or non-functional. In addition, renal angiomyolipomas, bronchial carcinoids, and gastroenteropancreatic neuroendocrine tumors have been described, along with tumors of the uterus, adrenal glands, and thyroid.

The earliest initial manifestation was a case of acromegaly in a 30-year-old patient.

Medullary thyroid carcinomas and pheochromocytomas, and tumors from the spectrum of MEN2 do not occur with MEN4.

Therapeutic Considerations

The treatment of individual cases is similar to that of MEN1.

Surveillance Recommendations

Surveillance Recommendations

Due to the limited numbers of patients, there are not yet any standard recommendations for early detection. The following recommendations are made on the basis of previous observations:

Regular Clinical Examinations Starting in Childhood

  • GH excess: gigantism, acromegaly?

  • Glucocorticoid excess: Cushing syndrome?

  • Anthropometric measurements, entering the values in percentile curves

Laboratory Testing (Annual)

  • Starting in childhood: serum calcium level corrected for serum albumin

  • Starting in adolescence: IGF-1

Additional Information

Open Clinical Trials / Registries

There are currently no open clinical trials/registries for patients with Multiple endocrine neoplasia Type 4 that we can recommend to you for more information.

Support Groups

Unfortunately, we are as yet unaware of any existing support groups for patients with multiple endocrine neoplasia type 4. We will add new information as it becomes available.