Chapter 4 - Functioning Pituitary Adenomas

Abstract

Many molecular genetic abnormalities have been recognized in the setting of anterior pituitary adenomas. However, pituitary adenomas with heritable genetic causes are rare and have been described most often in the setting of an endocrine tumor syndrome, such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). MEN1 is an autosomal dominant condition that is associated with the occurrence of parathyroid, enteropancreatic, and anterior pituitary tumors. Endocrine-inactive tumors, such as lipomas and angiofibromas, are also frequently seen in MEN1 patients. The MEN1 gene on chromosome 11q13 encodes the nuclear protein, menin. MEN1 appears to act as a tumor suppressor gene, and recent data suggest that menin can potentially interact with thousands of genes, 3′ sites and in chromatin. To date, over 500 different individual mutations in the MEN1 gene have been described, most of which predict a truncated menin protein. However, in 20–30% of cases suggestive of MEN1 clinically, the MEN1 sequence is normal. About 40% of patients with MEN1 have pituitary adenomas, and 17% of cases present with a pituitary tumor. Patients with pituitary tumors present earlier than patients presenting with other MEN1 tumors. In families with MEN1, pituitary tumors are more frequent than in sporadic MEN1. From a clinical perspective, MEN1-associated pituitary adenomas are more aggressive and less responsive to treatment than sporadic non-MEN1 tumors.