OC06 - AIP variants among adult patients with acromegaly

Abstract Background/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. Purpose We studied the prevalence of AIP variants in a cohort of unselected, consecutive adult patients with acromegaly from 2019 to 2024. 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 mixed tumour (prolactin co-secretion). Additionally, 50% of AIP variant carriers met the criteria for familial isolated pituitary adenoma (FIPA). Conclusion(s) This study shows 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.