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

Best Pract Res Clin Endocrinol Metab. 2024 Jul;38(4):101910. doi: 10.1016/j.beem.2024.101910. Epub 2024 Jun 29.

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.

Keywords: GHR 1–241, MeSH unique ID: C517401; inappropriate growth hormone secretion syndrome (acromegaly), MeSH unique ID: D000172; pegvisomant, MeSH Unique ID: C406545; pituitary gigantism, MeSH unique ID: D005877; somatostatin analogue CTAP, MeSH unique ID: C529311.

Publication types

  • Review

MeSH terms

  • Acromegaly / drug therapy
  • Human Growth Hormone* / analogs & derivatives
  • Human Growth Hormone* / therapeutic use
  • Humans
  • Receptors, Somatotropin* / antagonists & inhibitors

Substances

  • pegvisomant
  • Human Growth Hormone
  • Receptors, Somatotropin

Supplementary concepts

  • Growth hormone excess