title: Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly.
abstract: BACKGROUND
  Sensitivity to pegvisomant therapy is highly variable in patients with acromegaly but determinants of this variability are still unknown. Lack of exon 3 (d3-) of the growth hormone (GH) receptor (GHR) has been associated with increased biological activity of GH.
  
  
  OBJECTIVE
  To assess whether the presence of d3-GHR haplotype may have a role in predicting dose regimen and response to pegvisomant in acromegaly.
  
  
  METHODS
  Case series. Setting Institutional referral center at a tertiary care hospital. Patients Nineteen acromegalic patients with active disease after unsuccessful neurosurgery and somatostatin analog therapy.
  
  
  METHODS
  Before and 1, 3, 6 and 12 months after treatment with pegvisomant, IGF-I; GH receptor genotype, determined from peripheral blood by polymerase chain reaction. All patients started treatment with pegvisomant at 10 mg/daily and then increased the dose, according to a fixed schedule, during a 12-month follow-up until normalization of IGF-I levels.
  
  
  RESULTS
  d3-GHR patients required a significant lower dose of pegvisomant and shorter treatment time to normalize IGF-I.
  
  
  CONCLUSIONS
  The GHR genotype could be useful in predicting dose and individual response to pegvisomant in acromegaly.
authors.affiliation: Division of Endocrinology, School of Medicine, Catholic University, Largo A. Gemelli, 8, 00168, Rome, Italy, abianchi69@yahoo.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bianchi
authors.forename: Gherardo
authors.initials: G
authors.lastname: Mazziotti
authors.forename: Laura
authors.initials: L
authors.lastname: Tilaro
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cimino
authors.forename: Flora
authors.initials: F
authors.lastname: Veltri
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gaetani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pecorini
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.forename: Andrea
authors.initials: A
authors.lastname: Giustina
authors.forename: Laura
authors.initials: L
authors.lastname: De Marinis
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D005091:Exons / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011986:Receptors, Somatotropin / Q000235:genetics*; D055815:Young Adult
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant