Endocrine Abstracts

JOINT3942

Introduction: AIP variants are found in up to 40% of familial cases of acromegaly and gigantism, as well as in some sporadic cases, particularly those with early-onset disease. Patients with AIP variants often present with higher growth hormone (GH) levels. AIP variants are found in up to 40% of familial cases of acromegaly and gigantism, as well as in some sporadic cases, particularly those with early-onset disease. Patients with AIP variants often present with higher growth hormone (GH) levels with no difference in insulin growth factor 1 (IGF-1) level.

Objectives: We studied the prevalence of AIP variants in a cohort of unselected, consecutive adult patients with acromegaly from 2019 to 2024.

Materials and methods: A total of 134 patients (79 females, 55 males, age range 16-75 years) with somatotroph pituitary neuroendocrine tumor who were studied at the Jagiellonian University (Krakow), a tertiary referral center, were enrolled in this study. Genetic testing (Sanger Sequencing) was performed in all patients with acromegaly.

Results: Germline AIP variants were identified in eight patients including five missense variants, one three-nucleotide deletion. The specific variants observed were c.47G>A (p.Arg16His) in three patients, c.911G>A (p.Arg304Gln) in one female patient, c.235A>C (p.Thr79Pro) in one male patient, c.941G>C (p.Arg314Pro) in one male patient, c.811C>T (p.Arg271Trp) in one male patient, and c.742_744del (p.Tyr248del) in one female patient. The clinical significance of .47G>A and c.911G>A remains uncertain and is currently under discussion. The median age of symptom onset was 34 years (range: 14–71 years), while the median age at diagnosis was 39 years (range: 16–72 years). Most cases (7 out of 8) presented with macroadenomas, and six patients were not cured following surgery. Three patients harbored mix tumour (prolactin co-secretion). Additionally, 50% of AIP variant carriers met the criteria for familial isolated pituitary adenoma (FIPA).

Conclusions: This study show the prevalence of AIP variants among adult patients with acromegaly in Poland. Genetic testing in acromegaly should be considered to personalize and optimize the treatment of patients.