Clinical and genetic aspects of familial isolated pituitary adenomas

Abstract

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.

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

“…The first description of AIP mutations was performed with a large group of patients with familial acromegaly/gigantism from Finland (42). Other authors have published similar data (41,180). Two Brazilian siblings with acromegaly and GH-secreting PITs were clinically reported in 2001, and a heterozygous AIP mutation was documented soon after (42,176).…”

“…Up to 25% of all FIPA cases harbor a germline AIP mutation, although AIP germline mutations have rarely been detected in apparently sporadic PITs. However, a high prevalence of AIP mutations in macroadenoma cases younger than 30 years of age (10%) and in children with macroadenomas (>20%) have been verified (180). Furthermore, FIPA may have a relatively high prevalence in the general population because it accounts for up to 2-3% of PITs in some series.…”

Pituitary adenoma: a literature review

“…Mo le ku li niø ty ri mø me tu bu vo at ras ti ke li ge ne ti niai ir epi ge ne ti niai pa ki ti mai, ku rie su ke lia mu ta ci jas: so ma ti nës mu ta ci jos GSP ge ne, PTTG pa di dë ju si eks pre si ja, làs te lës cik lo re gu lia ci jos ir sig na li niø ke liø su tri ki mai. La bai re tai HA su ke lia kla si kiniø on ko ge nø mu ta ci jos [15,16].…”

“…Pas ta ra jai HA gru pei pri klau so MEN sin dro mo 1 ti pas, Car ney kom plek sas, izo liuo ta ðei mi në ade no ma ir nau jai api brëþ tas MEN sin dro mo 4 ti pas [15].…”

“…Anks èiau bu vo ið ski ria ma tik izo liuo ta ðei mi në so ma tot ro pi no ma, ta èiau ðis skirs ty mas bu vo per siau ras, nes mi në tas pa vel dë ji mas bû din gas ir pro lak ti no moms bei ki toms ade no moms. Ge riau siai ið tir ta ðei mi në ak ro me ga li ja: 2006 m. Vie ri maa ir ben dra au to riai nu sta të, kad jà su ke lia AIP ge no, esan èio 11 chro mo so mos il go jo pe ties 13.3 re gio ne, mu ta ci ja [15,17,21]. Në ra aið -ku, kaip ji da ly vau ja na vi ko pa to ge ne zë je.…”