Pituitary adenomas occur in a familial setting in multiple endocrine neoplasia 
type 1 (MEN1) and Carney's complex (CNC), which occur due to mutations in the 
genes MEN1 and PRKAR1A respectively. Isolated familial somatotropinoma (IFS) is 
also a well-described clinical syndrome related only to patients with 
acrogigantism. Pituitary adenomas of all types--not limited to IFS--can occur in 
a familial setting in the absence of MEN1 and CNC; this phenotype is termed 
familial isolated pituitary adenomas (FIPA). Over the past 7 years, we have 
described over 90 FIPA kindreds. In FIPA, both homogeneous and heterogeneous 
pituitary adenoma phenotypes can occur within families; virtually all FIPA 
kindreds contain at least one prolactinoma or somatotropinoma. FIPA differs from 
MEN1 in terms of a lower proportion of prolactinomas and more frequent 
somatotropinomas in the FIPA cohort. Patients with FIPA are significantly 
younger at diagnosis and have significantly larger pituitary adenomas than 
matched sporadic pituitary adenoma counterparts. A minority of FIPA families 
overall (15%) exhibit mutations in the aryl hydrocarbon receptor-interacting 
protein (AIP) gene; AIP mutations are present in only half of IFS kindreds 
occurring as part of the FIPA cohort. In families with AIP mutations, pituitary 
adenomas have a penetrance of over 50%. AIP mutations are extremely rare in 
patients with sporadic pituitary adenomas. This review deals with pituitary 
adenomas that occur in a familial setting, describes in detail the clinical, 
pathological, and genetic features of FIPA, and addresses aspects of the 
clinical approach to FIPA families with and without AIP mutations.