What is multiple endocrine neoplasia type 4?

Multiple endocrine neoplasia type 4 (MEN4) is a genetic – or hereditary – disease caused by genetic changes in the CDKN1B gene. Those affected have a greatly increased risk of developing tumors of the parathyroids along with primary hyperparathyroidism (PHPT) and tumors of the anterior pituitary (anterior pituitary neuroendocrine tumors, PitNET). MEN4 is therefore like the clinical picture of multiple endocrine neoplasia type 1 (MEN1). In addition, benign tumors of the kidney (angiomyolipomas), hormone-active tumors of the gastrointestinal tract and the pancreas, and tumors of the uterus, adrenal glands, and thyroid may occur.

How is multiple endocrine neoplasia type 4 diagnosed?

Genetic Diagnostics

Genetic diagnostics for a mutation of the CDKN1B gene should be conducted for all people with PHPT for whom no genetic change in the MEN1 gene has been found.

What is the risk of cancer?

So far, PHPT has been diagnosed in all patients with a CDKN1B mutation, and it is common for tumors of the anterior pituitary (PitNET) to occur. In addition, benign tumors of the kidney (angiomyolipomas), hormone-active tumors of the gastrointestinal tract and the pancreas, and tumors of the uterus, adrenal glands, and thyroid may occur.

Due to the small numbers of patients, no data on the risk of the individual diseases is currently available.

The earliest initial manifestation was a case of acromegaly (enlargement of hands, feet, ears, nose, and chin) in a 30-year-old patient.

What causes multiple endocrine neoplasia type 4?

MEN4 is caused by a mutation – or genetic change – in the CDKN1B gene. This gene encodes for p27kip1, a protein that blocks the amplification of genetic material under normal conditions. Now if the CDKN1B gene is altered, the protein no longer functions properly, meaning that the genetic material wis amplified excessively, allowing tumors to develop.

MEN4 can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease.

Is there a treatment?

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

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

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

Regular Clinical Examinations Starting in Childhood

  • Is gigantism or acromegaly (enlargement of hands, feet, ears, nose chin) present? This would be a sign of growth hormone excess as with PitNET.

  • Is Cushing syndrome (“moon face,” central obesity, “bull neck,” increased blood pressure, etc., etc.) present? This would be a sign of glucocorticoid excess as with PitNET.

  • Measurements of physical size and entering the values in percentile curves

Blood Tests (annual)

  • Starting in childhood: serum calcium corrected for serum albumin

  • Starting in adolescence: IGF-1

Self-Care and Support

What should I pay special attention to?

What do I need to pay close attention to?
Hyperparathyroidism may present itself through bone pain. In addition, kidney or gall stones may occur and cause pain in the area of the flanks and/or upper abdomen.

Hypophyseal tumors can cause headaches, visual disturbances, or even hormonal disorders that manifest in gigantism, acromegaly or Cushing syndrome (see surveillance measures for early detection).

Should you notice one of the above-mentioned signs or other complaints or symptoms listed above, be sure to see a doctor right away.

Support Groups and Additional Information

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.