EYES2023 ESE Young Endocrinologists and Scientists (EYES) 2023 Oral communication 4: Pituitary and Neuroendocrinology (8 abstracts)
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
Flavia Costanza 1 , Sabrina Chiloiro 2 , Antonella Giampietro 3 , Pier Paolo Mattogno 3 , Amato Infante 3 , Flavia Angelini 3 , Liverana Lauretti 3 , Alessandro Olivi 3 , Alfredo Pontecorvi 3 , Francesco Doglietto 3 , Laura De Marinis 3 & Antonio Bianchi 3
1Catholic University of the Sacred Heart – Fondazione Policlinico Universitario A. Gemelli Irccs, Endocrinology and Diabetology, Rome, Italy; 2Department of Endocrinology, Catholic University of the Sacred Heart, Rome, Italy; 3Catholic University of the Sacred Heart-Fondazione Policlinico Universitario A. Gemelli Irccs.
Background: Acromegaly is associated with skeletal fragility and increased prevalence of vertebral fractures (VF). In recent years several authors tried to investigate predictor markers of bone fragility risk in this endocrine disorder. 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).
Objectives: We conducted a longitudinal, retrospective, observational, single-center study to investigate the role of GHR polymorphisms as prognostic factor of incidental VF (I-VF) in first-generation somatostatin analogs (SSAs)-resistant acromegalic patients and treated with GHR antagonist (Pegvisomant) or second-generation somatostatin analogs (Pasireotide Lar).
Methods: 72 patients with acromegaly were included in our study. 28 patients carried d3-GHR isoform, and 44 patients carried fl-GHR isoform. At baseline, all patients were affected by active acromegaly: 46 patients were treated with Pegvisomant, in combination with first-generation SSAs, and 26 were treated with Pasireotide Lar. At the last follow-up, 58 patients achieved biochemical control of acromegaly. 18 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 first-generation SSAs, 32 patients carried fl-GHR polymorphism and 14 carried d3-GHR polymorphism. From the group treated with Pasireotide Lar, 12 patients carried fl-GHR isoform and 14 patients carried d3-GHR isoform. I-VF occurred more frequently in patients carrying the fl-GHR isoform compared to d3-GHR (P=0.04); otherwise, I-VF occurred more frequently in patients carrying the 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).
Conclusions: The GHR polymorphisms could improve the therapeutic approach in acromegaly, tailored to the individual patient, in the context of personalized medicine.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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