The Role of the GH Receptor Polymorphisms as a Prognostic Factor of Vertebral Fractures in Acromegalic Patients Resistant to First-generation SSAs and Treated with Pegvisomant or Pasireotide LAR

Title:The Role of the GH Receptor Polymorphisms as a Prognostic Factor of Vertebral Fractures in Acromegalic Patients Resistant to First-generation SSAs and Treated with Pegvisomant or Pasireotide LAR

Volume: 24

Author(s): Flavia Costanza*, Sabrina Chiloiro, Antonella Giampietro, Flavia Angelini, Amato Infante, Alfredo Pontecorvi, Laura De Marinis and Antonio Bianchi

Affiliation:

• Department of Endocrinology, Diabetology and Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
• Department of Translational Medicine, Catholic University of the Sacred Heart, Rome, Italy

Abstract:

Background: Acromegaly is associated with skeletal fragility and increased prevalence of vertebral fractures (VF). Two isoforms of GH receptor (GHR) have been described, 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).

Objective: We conducted a longitudinal, retrospective, observational, single-center study to investigate the role of GHR polymorphism as a prognostic factor of incidental VF (I-VF) in firstgeneration somatostatin analogs (fg-SSAs)-resistant acromegalic patients and treated with Pegvisomant or Pasireotide LAR.

Methods: Seventy-two patients with active acromegaly were included: 28 patients carried the d3-GHR isoform, and 44 patients carried the fl-GHR isoform. Forty-six patients were treated with Pegvisomant in combination with fg-SSAs, and 26 were treated with Pasireotide LAR. At the last follow-up, 58 patients achieved biochemical control of acromegaly. Eighteen patients carried prevalent VF (P-VFs), while 14 patients experienced the occurrence of I-VFs.

Results: From the group treated with Pegvisomant in combination with fg-SSAs, 32 patients carried the fl-GHR isoform, and 14 carried the d3-GHR isoform. From the group treated with Pasireotide LAR, 12 patients had the fl-GHR isoform, and 14 patients carried the d3-GHR isoform. I-VF occurred more frequently in patients with the fl-GHR isoform compared to d3-GHR (p =0.04); otherwise, I-VF occurred more frequently in patients with the d3-GHR isoform than fl-GHR (p =0.01).

Conclusion: The GHR polymorphisms could improve the therapeutic approach in acromegaly, tailored to the individual patient, in the context of personalized medicine.

Cite this article as:

Costanza Flavia*, Chiloiro Sabrina, Giampietro Antonella, Angelini Flavia, Infante Amato, Pontecorvi Alfredo, De Marinis Laura and Bianchi Antonio, The Role of the GH Receptor Polymorphisms as a Prognostic Factor of Vertebral Fractures in Acromegalic Patients Resistant to First-generation SSAs and Treated with Pegvisomant or Pasireotide LAR, Endocrine, Metabolic & Immune Disorders - Drug Targets 2024; 24 () . https://dx.doi.org/10.2174/0118715303322301240610111946