Endocrine Abstracts

Genetic predisposition to pituitary adenomas is increasingly recognized and extends beyond diseases such as MEN1 and Carney complex to familial isolated pituitary adenomas (FIPA). A genetic predisposition occurs in >5% of all pituitary adenoma cases, with MEN1 and FIPA comprising the vast majority of these. The identification of the AIP gene as a predisposition gene for pituitary adenomas in 15–25% of FIPA kindreds and in a significant number of young patients with macroadenomas has stimulated much debate about familial screening and early diagnosis. In addition the MEN1-like (MENX or MEN4) caused by germline CDKN1B mutations adds to the complexity of testing choices. Clearly a systematic evaluation of familiarity and associated diseases in patients with pituitary adenomas would be helpful for clinical endocrinologists and geneticists alike.

Screening guidelines are already in place for MEN1 and the clinical features and associations of MEN1 related diseases are well established. Pituitary tumors in Carney complex are a less common disease manifestation that occur generally within the setting of more clearly diagnostic extra-pituitary manifestations.

AIP mutation-related pituitary adenomas are characterized by an early onset (50% before the age of 18 years) and a large predominance of somatotropinomas (80%) followed by mixed GH/PRL-secreting tumors, prolactinomas, and non-secreting adenomas. These tumors are usually large at diagnosis and appear to be more frequently resistant to pharmacological treatment.

Based on the demonstrated clinical characteristics of AIP mutation related pituitary adenoma patients, it is reasonable to systematically assess FIPA kindreds for AIP mutations. Similarly, patients with apparently sporadic aggressive adenomas diagnosed at age <30 years is a clinically well-delineated population that is enriched for AIP mutation positive cases Children with pituitary adenomas should be assessed for AIP mutations and consideration given to MEN1 testing also. In the case of AIP mutations, the risk for unaffected mutation carriers remains unclear. A pragmatic approach would be to offer regular hormonal assessments and an initial MRI; the optimal interval for follow up surveillance remains to be determined.