Pituitary adenomas are one of the most frequent intracranial tumors and occur 
with a prevalence of approximately 1:1000 in the developed world. Pituitary 
adenomas have a serious disease burden, and their management involves 
neurosurgery, biological therapies, and radiotherapy. Early diagnosis of 
pituitary tumors while they are smaller may help increase cure rates. Few 
genetic predictors of pituitary adenoma development exist. Recent years have 
seen two separate, complimentary advances in inherited pituitary tumor research. 
The clinical condition of familial isolated pituitary adenomas (FIPA) has been 
described, which encompasses the familial occurrence of isolated pituitary 
adenomas outside of the setting of syndromic conditions like multiple endocrine 
neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of 
pituitary adenomas and represent a clinical entity with homogeneous or 
heterogeneous pituitary adenoma types occurring within the same kindred. The 
aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as 
causing a pituitary adenoma predisposition of variable penetrance that accounts 
for 20% of FIPA families. Germline AIP mutations have been shown to associate 
with the occurrence of large pituitary adenomas that occur at a young age, 
predominantly in children/adolescents and young adults. AIP mutations are 
usually associated with somatotropinomas, but prolactinomas, nonfunctioning 
pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types 
can also occur. Gigantism is a particular feature of AIP mutations and occurs in 
more than one third of affected somatotropinoma patients. Study of pituitary 
adenoma patients with AIP mutations has demonstrated that these cases raise 
clinical challenges to successful treatment. Extensive research on the biology 
of AIP and new advances in mouse Aip knockout models demonstrate multiple 
pathways by which AIP may contribute to tumorigenesis. This review assesses the 
current clinical and therapeutic characteristics of more than 200 FIPA families 
and addresses research findings among AIP mutation-bearing patients in different 
populations with pituitary adenomas.