title: Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly.
abstract: OBJECTIVE
  To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome.
  
  
  METHODS
  Seventeen patients (6 women), mean age 46·3 years (range: 23·2-76·2), were studied. For each patient, four hospital visits were identified including 'active disease' (no treatment) and last follow-up. At each visit, 12 blood samples were drawn during 3 h including an oral glucose tolerance test (OGTT). Eight patients received a somatostatin analogue in addition to pegvisomant on the last visit.
  
  
  RESULTS
  Median (range) pegvisomant doses (mg/day) were 10 (10-10), 15 (10-15) and 15 (10-15) at visits 2, 3 and 4, respectively, and the mean duration of pegvisomant treatment was 17·5 ± 3·2 (SEM) months. Serum IGF-I changed significantly during the treatment period with the highest level at baseline and lowest levels at visits 3 and 4. GH levels increased in a dose-dependent manner during pegvisomant treatment and decreased at visit 4. Changes in IGF-I levels correlated negatively with changes in serum pegvisomant levels between visits. Serum pegvisomant at each visit correlated with baseline growth hormone levels, whereas no associations between serum pegvisomant and either dose, gender, age or body weight were found.
  
  
  CONCLUSIONS
  (1) Serum GH levels increased initially, but remained stable during prolonged pegvisomant treatment in patients with acromegaly, (2) serum pegvisomant levels predicted the reduction in serum IGF-I during treatment and (3) the interindividual variation in serum pegvisomant levels seems not predicted by either age, gender or body composition.
authors: Department of Endocrinology and Internal Medicine MEA, Aarhus University Hospital, Aarhus, Denmark.
authors: Michael
authors: M
authors: Madsen
authors: Sanne
authors: S
authors: Fisker
authors: Ulla
authors: U
authors: Feldt-Rasmussen
authors: Mikkel
authors: M
authors: Andreassen
authors: Lars Østergaard
authors: LØ
authors: Kristensen
authors: Hans
authors: H
authors: Ørskov
authors: Jens Otto L
authors: JO
authors: Jørgensen
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D013006:Growth Hormone; C406545:pegvisomant