Endocrine Abstracts

Up to 5% of all pituitary tumors are hereditary (e.g. due to menin or AIP genes mutations). AIP gene mutations are more common in subjects with acromegaly, less than 30 years old at the onset of disease, and with FIPA family history. The study was aimed at the assessment of the frequency and characteristics of AIP-mutation related tumors in non-selected patients with pituitary macroadenomas.

Material and Methods: The study included subsequent 131 patients (57 males, 74 females; median age 42 years (IQR 25 years) diagnosed with pituitary macroadenomas, and with a negative family history of FIPA or MEN1 syndromes. The following tumors were identified: 11 ACTH-secreting, 49 GH-secreting (including 7 pluri-hormonal ones), 6 gonadotropinomas, 23 prolactinomas, 1 TSH-oma, and 43 non-secreting adenomas. Sanger sequencing was used for the assessment of AIP gene variants. The study was approved by the Ethics Board of JUMC.

Results: An AIP mutation was identified in five of 131 included subjects (3.8%): one diagnosed with Cushing’s disease, two with acromegaly, and two with non-secreting adenomas. In two patients, the identified mutation usually predisposes to ACTH-secreting adenomas, in two patients – mutations of unknown clinical significance were found (usually connected with pituitary adenomas), and the mutation detected in one patient was described as benign. Patients harboring hereditary AIP gene variations did not differ from the rest of the study group in median age at diagnosis (41 vs 42.5 years, P = 0.8), median largest tumor diameter (25 vs 24 mm, P = 0.6), gender distribution (60% of females vs 56.3%, P = 0.8), secreting tumor frequency (60% vs 67.5%, P = 0.7), or acromegaly diagnosis frequency (40% vs 37.3%, P = 0.9). 2 of the 5 patients with identified AIP gene mutations agreed for their families to be offered AIP genetic testing: (1) An AIP mutation was found in the asymptomatic mother of one acromegalic female patient. (2) The AIP mutation of unknown clinical significance was detected in the son of a male patient with acromegaly, clinically unscreened yet.

Conclusions: In our series of apparently sporadic pituitary macroadenomas, AIP gene mutation carriers did not differ substantially from patients with negative genetic testing. A risk factor-centered approach to AIP genetic screening may result in missing germline mutations, therefore, there is a need to establish if such a situation negatively impacts a patient’s and his/her family outcomes.