Clinical use a of growth hormone receptor antagonist in the treatment of acromegaly

The elucidation of the mechanisms by which growth hormone (GH) interacts wi th its receptor has facilitated the design of compounds that function as GH -receptor antagonists. One such compound, B2036, has been conjugated to pol yethylene glycol to produce a drug, pegvisomant, that has a powerful abilit y to lower circulating concentrations of insulin-like growth factor I (IGF- 1), the principal mediator of GH action, in patients with acromegaly and to improve the symptoms and signs associated with GH excess. This article des cribes the mechanism of action of GH-receptor antagonists, reviews the prec linical and clinical data on the use of pegvisomant and discusses some of t he challenges that lie a head in judging the efficacy of a treatment that, unlike established therapies for acromegaly, does not aim to modify the und erlying cause of acromegaly, namely excess GH secretion, but aims to lower serum IGF-1 levels to normal.