Endocrine Abstracts

Introduction: Acromegaly is the most genetically determined pituitary disease.

Objectives: We studied the prevalence of syndromic disease and germline mutations (AIP, MEN1, GNAS, PRKAR1A, CDKN1b) in a cohort of unselected, consecutive patients with acromegaly.

Materials and methods: A total of 133 patients (79 females, 54 males, age range 16–75 years) with somatotroph pituitary neuroendocrine tumor who were studied at the Jagiellonian University (Krakow), a tertiary referral center, between 2019 and 2022, were enrolled in this study. AIP testing was performed in all patients with acromegaly, whereas other genes were tested in young patients (<30 years-old), patients with macroadenoma or with syndromic features. Sanger sequencing was used for the assessment of AIP, MEN1, GNAS, PRKAR1A, CDKN1B gene variants, and multiplex ligation-dependent probe amplification (MLPA) was used for the assessment of PRKAR1A negative results in Sanger sequencing.

Results: Overall, a total of 12.2% (16/131) patients presented clinical manifestations of syndromic disease or gene variants which might be associated with acromegaly.

AIP variants were identified in 7.7% (8/104), MEN1 alterations were detected in 3.6% (3/84), McCune-Albright syndrome was clinically diagnosed in one patient (0.75%), one patient was clinically diagnosed with Carney complex (0.75%), and three patients presented MEN1 associated symptoms (acromegaly and hyperparathyroidism) with negative genetic evaluation for MEN1 and CDKN1B (Sanger sequencing). One patient presented Neurofibromatosis type 1 features, two additional patients presented some of Carney complex symptoms. None of patients harbored PRKAR1A and CDKN1B variants. Further confirmatory genetic analysis are planned in patients with clinical suspicion of syndromic disease and negative Sanger and MLPA testing.

Conclusions: This study is one of the first to show genetic abnormalities among adult patients with acromegaly in Poland. Genetic testing in acromegaly should be considered to personalize and optimize the treatment of patients.