gene germline variants in adult Polish patients with apparently sporadic pituitary macroadenomas.

Introduction: Up to 5% of all pituitary tumors are hereditary due to or aryl hydrocarbon receptor-interacting protein () genes mutations.

Objectives: The study was aimed at the assessment of the frequency and characteristics of -mutation related tumors in patients with apparently sporadic pituitary macroadenomas in the Polish population.

Materials And Methods: The study included 131 patients (57 males, 74 females; median age 42 years) diagnosed with pituitary macroadenomas, and with a negative family history of familial isolated pituitary adenoma (FIPA) or multiple endocrine neoplasia type 1 (MEN1) syndromes. Sanger sequencing was used for the assessment of gene variants. The study was approved by the Ethics Board of JUMC.

Results: variants were identified in five of the 131 included subjects (3.8%): one diagnosed with Cushing's disease, two with acromegaly, and two with non-secreting adenomas. Patients harboring hereditary gene alterations did not differ from the rest of the study group in median age at diagnosis (41.0 vs. 42.5 years, P=0.8), median largest tumor diameter (25 vs. 24 mm, P=0.6), gender distribution (60.0% vs. 56.3% females, P=0.8), secreting tumor frequency (60.0% vs. 67.5%, P=0.7), or acromegaly diagnosis frequency (40.0% vs.37.3%, P=0.9).

Conclusions: In our series of apparently sporadic pituitary macroadenomas, gene variant carriers did not differ substantially from patients with negative genetic testing. A risk factor-centred approach to genetic screening may result in missing germline variants. Considering the clinical impact of such genetic variants and their relatively low penetrance, it is, however, doubtful if general genetic screening benefits the whole cohort of pituitary macroadenoma patients and their families.