endocrine and metabolic disorders
Multiple Endocrine Neoplasia, Type 4 (MEN 4)
Introduction
Multiple endocrine neoplasia, type 4 (MEN 4) is an autosomal dominant syndrome characterized by adenomas and sometimes hyperplasia of the parathyroid glands and tumors of the pancreatic islet cells and/or pituitary gland. Hyperparathyroidism and asymptomatic hypercalcemia commonly occur. Diagnosis is by hormonal and imaging tests. Tumors causing symptoms are surgically removed when possible. Tumors are removed surgically if they cause symptoms or for suspected malignancy based on size criteria. MEN 4 is caused by an inactivating mutation of theCDKN1Bgene, which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. The protein is involved in cellular growth and development and has an important role in regulating the cell cycle. It acts as a tumor suppressor and when the protein is lost, cells can undergo unscheduled replication, which may eventually lead to cancer. Although MEN 4 involves the same primary organs as MEN 1 (parathyroids, pancreas, and pituitary), patients tend to present later in life and have a more indolent course of disease than those with MEN 1. MEN 4 is much less common that MEN 1, with fewer than 100 patients currently described in the world literature. 