Update on familial pituitary tumors: from multiple endocrine neoplasia type 1 to familial isolated pituitary adenoma.

BACKGROUND: Pituitary adenomas occur in a familial setting in about 5% of all cases and over half of these are due to multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Since the late 1990s, we have described non-MEN1/CNC familial pituitary tumors that include all tumor phenotypes and have named this condition 'familial isolated pituitary adenoma' (FIPA). Clinical features of FIPA differ from those of sporadic pituitary adenomas in that patients with FIPA are often younger and have larger tumors at diagnosis. About 15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates that FIPA may have a diverse genetic pathophysiology. We review the clinical features of FIPA, the tumor pathologies found in this setting and the genetic/molecular data that have been recently reported. CONCLUSIONS: Clinically relevant pituitary adenomas are more common than previously thought and occur in a familial setting in about 5% of cases overall. Therefore, specific questioning regarding family history of pituitary disease should be part of the workup of all patients with pituitary adenomas, not just those with acromegaly. FIPA is a useful clinical framework to study the features of pituitary adenomas that occur in a familial setting since it encompasses all tumor phenotypes and heterogeneous/homogeneous expression among affected family members.