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.

Abstract

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