title: Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
abstract: BACKGROUND
  Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.
  
  
  METHODS
  We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.
  
  
  RESULTS
  The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.
  
  
  CONCLUSIONS
  On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
authors.affiliation: Christie Hospital, Manchester, United Kingdom.
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
authors.forename: W M
authors.initials: WM
authors.lastname: Drake
authors.forename: L
authors.initials: L
authors.lastname: Katznelson
authors.forename: P U
authors.initials: PU
authors.lastname: Freda
authors.forename: V
authors.initials: V
authors.lastname: Herman-Bonert
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: E V
authors.initials: EV
authors.lastname: Dimaraki
authors.forename: P M
authors.initials: PM
authors.lastname: Stewart
authors.forename: K E
authors.initials: KE
authors.lastname: Friend
authors.forename: M L
authors.initials: ML
authors.lastname: Vance
authors.forename: G M
authors.initials: GM
authors.lastname: Besser
authors.forename: J A
authors.initials: JA
authors.lastname: Scarlett
authors.forename: M O
authors.initials: MO
authors.lastname: Thorner
authors.forename: C
authors.initials: C
authors.lastname: Parkinson
authors.forename: A
authors.initials: A
authors.lastname: Klibanski
authors.forename: J S
authors.initials: JS
authors.lastname: Powell
authors.forename: A L
authors.initials: AL
authors.lastname: Barkan
authors.forename: M C
authors.initials: MC
authors.lastname: Sheppard
authors.forename: M
authors.initials: M
authors.lastname: Malsonado
authors.forename: D R
authors.initials: DR
authors.lastname: Rose
authors.forename: D R
authors.initials: DR
authors.lastname: Clemmons
authors.forename: G
authors.initials: G
authors.lastname: Johannsson
authors.forename: B A
authors.initials: BA
authors.lastname: Bengtsson
authors.forename: S
authors.initials: S
authors.lastname: Stavrou
authors.forename: D L
authors.initials: DL
authors.lastname: Kleinberg
authors.forename: D M
authors.initials: DM
authors.lastname: Cook
authors.forename: L S
authors.initials: LS
authors.lastname: Phillips
authors.forename: M
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: C J
authors.initials: CJ
authors.lastname: Strasburger
authors.forename: S
authors.initials: S
authors.lastname: Hackett
authors.forename: K
authors.initials: K
authors.lastname: Zib
authors.forename: W F
authors.initials: WF
authors.lastname: Bennett
authors.forename: R J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000236:Adenoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000473:pathology; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*
chemical_list: D001323:Autoantibodies; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant