Growth hormone receptor antagonist pegvisomant and its role in the medical therapy of growth hormone excess

IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
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引用次数: 0

Abstract

Pegvisomant is a growth-hormone (GH) receptor antagonist that prevents the formation of the active heterotrimer of the dimerised GH receptor and the GH molecule necessary for downstream signal transduction. Over the past 20 years, it has become a key therapeutic option for physicians treating syndromes of GH/IGF-1 excess. Sufficient longitudinal follow-up data suggest that it can be deemed both safe and effective. It is the drug with the greatest potential for achieving an amelioration of the biochemical effects of GH excess with a corresponding normalisation of IGF-1 levels; however, insufficient dose titration has lessened real-world therapeutic outcomes. Theoretical concerns about stimulating tumour growth have been resolved as this has not been observed, while derangement of liver enzymes and local skin-related adverse reactions may occur in a minority of the patients. It may be a particularly impactful medication for the treatment of children, young people, and those with inherited disorders of GH excess, where other treatment modalities often fail. Combination therapy of pegvisomant with first- and second-generation somatostatin receptor ligands or with dopamine agonists remains an ongoing area of interest and research. High cost remains a barrier to the use of pegvisomant in many settings.

生长激素受体拮抗剂 pegvisomant 及其在生长激素过量医疗中的作用。
培维索孟是一种生长激素(GH)受体拮抗剂,能阻止二聚化的 GH 受体与下游信号转导所需的 GH 分子形成活性异三聚体。在过去的 20 年中,它已成为医生治疗 GH/IGF-1 过多综合征的主要治疗选择。充分的纵向跟踪数据表明,它既安全又有效。它是最有可能改善 GH 过多的生化效应并相应地使 IGF-1 水平恢复正常的药物;然而,剂量滴定不足降低了实际治疗效果。理论上对刺激肿瘤生长的担忧已经消除,因为尚未观察到这种情况,但少数患者可能会出现肝酶紊乱和局部皮肤相关不良反应。对于治疗儿童、青少年和患有遗传性 GH 过多症的患者来说,它可能是一种特别有影响力的药物,因为其他治疗方法往往无法奏效。培维索孟与第一代和第二代体生长抑素受体配体或多巴胺激动剂的联合治疗仍是一个值得关注和研究的领域。在许多情况下,高昂的费用仍然是使用培高索曼的障碍。
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来源期刊
CiteScore
11.90
自引率
0.00%
发文量
77
审稿时长
6-12 weeks
期刊介绍: Best Practice & Research Clinical Endocrinology & Metabolism is a serial publication that integrates the latest original research findings into evidence-based review articles. These articles aim to address key clinical issues related to diagnosis, treatment, and patient management. Each issue adopts a problem-oriented approach, focusing on key questions and clearly outlining what is known while identifying areas for future research. Practical management strategies are described to facilitate application to individual patients. The series targets physicians in practice or training.
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