Genetic Causes of Familial Pituitary Adenomas

Pituitary adenomas are benign intracranial neoplasms and clinically apparent pituitary adenomas have a prevalence of approximately 1:1,000 individuals. They usually arise sporadically, but familial pituitary adenomas comprise about 5% of all cases, more than half of which include multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). The other half is represented by familial isolated pituitary adenomas (FIPA), a clinical entity described in the late 1990s. Recently, interest has been focused on the genetic pathophysiology of familial pituitary adenomas. MEN1 is due to mutations in MEN1 gene. CNC is related to PRKAR1A mutations and still unknown disruptions on 2p16. Mutations of CDKN1B in MEN1-like patients without MEN1 mutations allowed the differentiation of the condition as MEN4. About 15% of FIPA kindreds are associated with aryl hydrocarbon receptor-interacting protein ( AIP ) gene mutations, which suggests that this is a genetically heterogeneous condition. Overall, familial pituitary adenomas represent a small proportion of pituitary tumors, but are particularly significant as affected individuals may be younger, and adenomas may be relatively difficult to treat.