title: Clinical use of a growth hormone receptor antagonist in the treatment of acromegaly.
abstract: The elucidation of the mechanisms by which growth hormone (GH) interacts with its receptor has facilitated the design of compounds that function as GH-receptor antagonists. One such compound, B2036, has been conjugated to polyethylene glycol to produce a drug, pegvisomant, that has a powerful ability to lower circulating concentrations of insulin-like growth factor I (IGF-I), the principal mediator of GH action, in patients with acromegaly and to improve the symptoms and signs associated with GH excess. This article describes the mechanism of action of GH-receptor antagonists, reviews the preclinical and clinical data on the use of pegvisomant and discusses some of the challenges that lie ahead in judging the efficacy of a treatment that, unlike established therapies for acromegaly, does not aim to modify the underlying cause of acromegaly, namely excess GH secretion, but aims to lower serum IGF-I levels to normal.
authors.affiliation: Department Endocrinology, St Bartholomew's Hospital, London, UK EC1A 7BE.
authors.forename: W M
authors.initials: WM
authors.lastname: Drake
authors.forename: C
authors.initials: C
authors.lastname: Parkinson
authors.forename: G M
authors.initials: GM
authors.lastname: Besser
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D015415:Biomarkers; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*
chemical_list: D015415:Biomarkers; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant