Pituitary adenomas represent a group of functionally diverse
neoplasms with relatively high
prevalence in the general
population. Most occur sporadically, but inherited genetic
predisposing factors are increasingly recognized. Familial isolated
pituitary adenoma is a recently defined clinical entity, and is characterized by hereditary presentation of
pituitary adenomas in the absence of clinical and genetic features of syndromic
disease such as
multiple endocrine neoplasia type 1 and
Carney complex. Familial isolated
pituitary adenoma is inherited in an autosomal dominant manner and accounted for approximately 2-3% of
pituitary tumors in some series.
Germline mutations in the aryl-
hydrocarbon interacting
protein gene are identified in around 25% of familial isolated
pituitary adenoma kindreds.
Pituitary adenomas with
mutations of the aryl-
hydrocarbon interacting
protein gene are predominantly somatotropinomas and
prolactinomas, but non-functioning
adenomas,
Cushing disease, and thyrotropinoma may also occur. These
tumors may present as macroadenomas in young
patients and are often relatively difficult to control. Furthermore, recent evidence indicates that aryl-
hydrocarbon interacting
protein gene mutations occur in >10% of
patients with sporadic macroadenomas that occur before 30 years of age, and in >20% of
children with macroadenomas.
Genetic screening for aryl-
hydrocarbon interacting
protein gene mutations is warranted in selected high-
risk patients who may benefit from early recognition and follow-up.