GH receptor polymorphisms guide second-line therapies to prevent acromegaly skeletal fragility: preliminary results of a pilot study.

Humans Acromegaly / drug therapy Male Female Middle Aged Retrospective Studies Pilot Projects Receptors, Somatotropin / genetics Somatostatin / analogs & derivatives Adult Human Growth Hormone / therapeutic use Aged Polymorphism, Genetic Longitudinal Studies
GH receptor acromegaly fracture osteopenia osteoporosis pasireotide pegvisomant somatostatin receptor ligands

Journal

Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782

Informations de publication

Date de publication:
2024
Historique:
received: 08 04 2024
accepted: 07 08 2024
medline: 16 9 2024
pubmed: 16 9 2024
entrez: 16 9 2024
Statut: epublish

Résumé

Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies. A longitudinal, retrospective, observational study was conducted on a cohort of 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide long-acting release). Second line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038). Our data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine.

Sections du résumé

Background UNASSIGNED
Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies.
Methods UNASSIGNED
A longitudinal, retrospective, observational study was conducted on a cohort of 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide long-acting release).
Results UNASSIGNED
Second line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038).
Conclusions UNASSIGNED
Our data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine.

Identifiants

DOI: 10.3389/fendo.2024.1414101 PMID: 39280003 PMC: PMC11395836
pubmed: 39280003
doi: 10.3389/fendo.2024.1414101
pmc: PMC11395836
doi:

Substances chimiques

pegvisomant N824AOU5XV
Receptors, Somatotropin 0
Somatostatin 51110-01-1
Human Growth Hormone 12629-01-5
pasireotide 98H1T17066

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1414101

Informations de copyright

Copyright © 2024 Chiloiro, Costanza, Giampietro, Infante, Mattogno, Angelini, Gullì, Lauretti, Rigante, Olivi, De Marinis, Doglietto, Bianchi and Pontecorvi.

Déclaration de conflit d'intérêts

SC, AB, AG, LDM have served as investigator for clinical trials funded by Novartis, Pfizer, Ipsen and Crinetics. SC and AB received grants from Pfizer. SC won the 2022 Arrigo Recordati Research Grant. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Auteurs

Sabrina Chiloiro (S)

Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Endocrinologia, Diabetologia e Medicina Interna, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Flavia Costanza (F)

Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Endocrinologia, Diabetologia e Medicina Interna, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Antonella Giampietro (A)

Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Endocrinologia, Diabetologia e Medicina Interna, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Amato Infante (A)

Dipartimento di Diagnostica per Immagini e radioterapia oncologica, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Pier Paolo Mattogno (PP)

Dipartimento di Neurochirugia, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.
Dipartimento di Science dell'invecchiamento, neuroscienze, delle scienze del capo-collo, ed ortopediche, Università Cattolica del Sacro Cuore, Rome, Italy.

Flavia Angelini (F)

Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Endocrinologia, Diabetologia e Medicina Interna, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Consolato Gullì (C)

Dipartimento di Diagnostica per Immagini e radioterapia oncologica, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Liverana Lauretti (L)

Dipartimento di Neurochirugia, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.
Dipartimento di Science dell'invecchiamento, neuroscienze, delle scienze del capo-collo, ed ortopediche, Università Cattolica del Sacro Cuore, Rome, Italy.

Mario Rigante (M)

Unità di Otorinologingoiatria, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Alessandro Olivi (A)

Dipartimento di Neurochirugia, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.
Dipartimento di Science dell'invecchiamento, neuroscienze, delle scienze del capo-collo, ed ortopediche, Università Cattolica del Sacro Cuore, Rome, Italy.

Laura De Marinis (L)

Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Endocrinologia, Diabetologia e Medicina Interna, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Francesco Doglietto (F)

Dipartimento di Neurochirugia, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.
Dipartimento di Science dell'invecchiamento, neuroscienze, delle scienze del capo-collo, ed ortopediche, Università Cattolica del Sacro Cuore, Rome, Italy.

Antonio Bianchi (A)

Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Endocrinologia, Diabetologia e Medicina Interna, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

Alfredo Pontecorvi (A)

Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Endocrinologia, Diabetologia e Medicina Interna, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › GH receptor polymorphisms guide second-line...
questionsmedicales.fr › Maladies endocriniennes › Maladies de l'hypophyse › Hyperpituitarisme › Acromégalie › GH receptor polymorphisms guide second-line...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › GH receptor polymorphisms guide second-line...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › GH receptor polymorphisms guide second-line...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones hypophysaires › Hormones antéhypophysaires › Hormone de croissance › Hormone de croissance humaine › GH receptor polymorphisms guide second-line...
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questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › GH receptor polymorphisms guide second-line...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études longitudinales › GH receptor polymorphisms guide second-line...