Multiple Endocrine Neoplasia Type 4 – Definition
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 the 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.
Synonym:
CDKN1B related MEN
Gene:
CDKN1B
Gene product:
p27kip1
Function:
The cyclin-dependent kinase inhibitor 1B is important in blocking the cell cycle.
Pattern of inheritance:
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
Multiple Endocrine Neoplasia Type 4 – Diagnosis
Genetic Diagnostics
Genetic diagnostics for a CDKN1B gene mutation are 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 the 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.
Special Features of Treatment
The treatment of individual cases is similar to that of MEN1.
Diagnosis of Multiple Endocrine Neoplasia Type 4- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of Multiple Endocrine Neoplasia Type 4- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
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
Multiple Endocrine Neoplasia Type 4 – Further Information
Further Information
Unfortunately, we are not yet aware of any support groups for patients with multiple endocrine neoplasia type 4. As soon as we have new information, we will add it.
