THU050 The Role Of The GH Receptor Polymorphism As Prognostic Factor Of Vertebral Fractures In Acromegaly Patients Resistant To First Generation SSAs And Treated With GH Receptor Antagonist Or Second Generation Somatostatin Ligand

Abstract

Abstract Disclosure: F. Costanza: None. S. Chiloiro: None. A. Giampietro: None. P. Mattogno: None. A. Infante: None. F. Angelini: None. L. Lauretti: None. A. Olivi: None. A. Pontecorvi: None. F. Doglietto: None. L. De Marinis: None. A. Bianchi: None. Acromegaly is associated with skeletal fragility and an increased prevalence of vertebral fractures (VF). In recent years several authors have tried to investigate the markers that can predict the risk of bone fragility in this endocrine disorder. Two different isoforms of the GH receptor (GHR) have been described so far, which differ in the presence or absence of a transcript of exon 3 of the GHR gene. Both isoforms produce a functional receptor, but the exon 3-deleted isoforms (d3-GHR) have greater sensitivity to endogenous and recombinant GH than the full-length isoform (fl-GHR). We conducted a longitudinal, retrospective, observational, single-center study of first-generation SSA-resistant acromegaly patients, with the aim of investigating the role of GHR polymorphism as a prognostic factor of incidental VF (I-VF) in first-generation SSA-resistant acromegalic patients and treated with GH receptor antagonist (Pegvisomant) or second-generation somatostatin ligand (Pasireotide Lar).72 patients with acromegaly were included. 28 patients carried d3-GHR isoform (38.9%) and 44 patients carried fl-GHR isoform (61.1%). At baseline, all patients were affected by active acromegaly; 46 patients were treated with Pegvisomant in combination with first generation SSA and 26 were treated with Pasireotide Lar. 18 patients (25%) carried P-VFs. At last follow-up, 58 patients achieved biochemical control of acromegaly (80.6%). 14 patients experienced the occurrence of I-VFs. From the group treated with Pegvisomant in combination with first generation SSA, 32 patients carried fl-GHR polymorphism and 14 carried d3-GHR polymorphism. At baseline, 10 patients (21.7%) were I-VF carriers. At follow-up, 8 patients developed P-VF (17.4%). I-VF occurred more frequently in patients carrying fl-GHR isoform compared to d3-GHR (p=0.04). From the group treated with Pasireotide Lar, 12 patients carried fl-GHR isoform and 14 patients carried d3-GHR isoform. At baseline, 8 patients (30.8%) were I-VF carriers. At follow-up, 6 patients developed P-VF (23.1%). I-VF occurred more frequently in patients carrying d3-GHR isoform than fl-GHR (p=0.01) and in patients with P-VF as compared to patients without P-VF (p=0.05).In conclusion, the GH receptor polymorphism could assume greater relevance as a prognostic factor of VF in acromegaly patients. In the future, the knowledge of the GHR polymorphism may improve the therapeutic approach of acromegaly patients, tailored to the individual patient, in the context of personalized medicine. Presentation: Thursday, June 15, 2023