Chiloiro Sabrina, Costanza Flavia, Giampietro Antonella, Infante Amato, Mattogno Pier Paolo, Angelini Flavia, Gullì Consolato, Lauretti Liverana, Rigante Mario, Olivi Alessandro, De Marinis Laura, Doglietto Francesco, Bianchi Antonio, Pontecorvi Alfredo
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.
Front Endocrinol (Lausanne). 2024 Aug 30;15:1414101. doi: 10.3389/fendo.2024.1414101. eCollection 2024.
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.
骨骼脆性的特征是肢端肥大症患者椎体骨折（VF）的发生率增加。已经进行了多项试验以确定VF的可改变危险因素和预测因素，但关于生长激素受体（GHR）异构体的预后作用的数据有限。在本研究中，我们调查了GHR多态性在接受二线药物治疗的患者中偶发性椎体骨折（i-VF）发生中的潜在作用。
对45例对第一代生长抑素受体配体（fg-SRL）无反应并接受GHR拮抗剂（培维索孟）或第二代SRL（长效帕瑞肽）治疗的肢端肥大症患者队列进行了一项纵向、回顾性、观察性研究。
26例患者接受培维索孟加fg-SRLs二线治疗，19例患者接受长效帕瑞肽二线治疗。在接受fg-SRLs + 培维索孟治疗的组中，18例患者（69.2%）鉴定出fl-GHR异构体，8例患者（30.8%）鉴定出d3-GHR异构体。i-VF仅出现在fl-GHR异构体携带者中（p = 0.039）。在接受长效帕瑞肽治疗的组中，11例患者（57.9%）鉴定出fl-GHR异构体，8例患者（42.1%）鉴定出d3-GHR异构体。i-VF仅出现在d3-GHR异构体携带者中（p = 0.018）。fl-GHR异构体患者接受fg-SRL + 培维索孟治疗时发生i-VF的风险较高（OR：1.6，95%CI：1.1 - 2.3，p = 0.04），而接受长效帕瑞肽治疗时风险较低（OR：0.26，95%CI：0.11 - 0.66，p = 0.038）。
我们的数据支持GHR异构体在接受二线药物治疗的肢端肥大症患者i-VF发生中的预测作用，可根据个体患者进行调整。在个性化医疗背景下，了解GHR多态性可能有助于二线治疗的选择，改善治疗方法。
