title: The Effect of the Exon-3-Deleted Growth Hormone Receptor on Pegvisomant-Treated Acromegaly: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist pegvisomant (PEGV) is highly effective in treating severe acromegaly. Response to PEGV treatment seems to be influenced by d3-GHR and appears to be more responsive to PEGV, although available results remain conflicting.
  
  
  OBJECTIVE
  To assess the influence of d3-GHR on the responsiveness of acromegaly patients to PEGV by compiling the evidence derived from the largest available studies.
  
  
  METHODS
  A systematic review of the literature identified three published studies and one conference abstract. Acromegaly patients (n = 324, 49.7% d3-GHR carriers) were treated with either PEGV monotherapy or PEGV combined with long-acting somatostatin analogues and/or cabergoline. A meta-analysis of raw data from these studies was performed.
  
  
  RESULTS
  No significant effect of the d3-GHR was observed while bringing insulin-like growth factor I (IGF-I) levels below the upper limit of normal with PEGV, which was defined as the lowest IGF-I level during PEGV treatment (mean difference: -2.3%; 95% CI: -6.5 to 1.8, p = 0.270). The PEGV dose required to achieve the lowest IGF-I levels was also not significantly influenced by individuals carrying d3-GHR (mean difference: 4.1 mg weekly; 95% CI: -5.1 to 13.2, p = 0.385). For both outcomes, separate analysis of PEGV monotherapy and combination treatment gave similar results.
  
  
  CONCLUSIONS
  Our findings suggest that the d3-GHR polymorphism has no effect on biochemical disease control in acromegaly, as it is not of added value for either the prediction of PEGV responsiveness or the determination of the required PEGV dose.
authors: Department of Internal Medicine, Endocrinology Section, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Sanne E
authors: SE
authors: Franck
authors: Linda
authors: L
authors: Broer
authors: Aart Jan
authors: AJ
authors: van der Lely
authors: Peter
authors: P
authors: Kamenicky
authors: Ignacio
authors: I
authors: Bernabéu
authors: Elena
authors: E
authors: Malchiodi
authors: Patric J D
authors: PJD
authors: Delhanty
authors: Fernando
authors: F
authors: Rivadeneira
authors: Sebastian J C M M
authors: SJCMM
authors: Neggers
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors* / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; C406545:pegvisomant
keywords: Acromegaly; Deletion of exon 3; Growth hormone receptor; Meta-analysis; Pegvisomant; Polymorphism