Pegvisomant in the treatment of acromegaly.
Epidemiological studies have highlighted the need for tight control of growth hormone (GH) and insulin-like growth factor I (IGF-I) in patients with acromegaly. Studies highlighting the events involved in GH receptor signaling have allowed the development of a pegylated GH receptor antagonist (pegvisomant) for use in humans, which has been designed to outcompete GH for the GH receptor, but which contains a position 120 amino acid substitution that prevents recruitment of a second GH receptor. This process of receptor dimerisation is crucial for signal transduction and IGF-I generation. Clinical trials of pegvisomant suggest it is the most effective treatment for acromegaly to date, as this therapy is capable of normalising serum IGF-I in up to 97% of patients when doses of 40 mg per day are used. This paper reviews the development of pegvisomant and the clinical experience in patients with acromegaly to date.
D000172:Acromegaly / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; C406545:pegvisomant