The Effect of the Exon-3-Deleted Growth Hormone Receptor on Pegvisomant-Treated Acromegaly: A Systematic Review and Meta-Analysis

Sanne E. Franck, Linda Broer, Aart Jan Van Der Lely, Peter Kamenicky, Ignacio Bernabéu, Elena Malchiodi, Patric J.D. Delhanty, Fernando Rivadeneira, Sebastian J.C.M.M. Neggers

Research output: Contribution to journalReview article

6 Citations (Scopus)

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. Design: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)131-140
Number of pages10
JournalNeuroendocrinology
Volume105
Issue number2
DOIs
Publication statusPublished - Aug 1 2017
Externally publishedYes

Fingerprint

Somatotropin Receptors
Acromegaly
Meta-Analysis
Exons
Insulin-Like Growth Factor I
pegvisomant
Somatostatin

Keywords

  • Acromegaly
  • Deletion of exon 3
  • Growth hormone receptor
  • Meta-analysis
  • Pegvisomant
  • Polymorphism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Franck, S. E., Broer, L., Van Der Lely, A. J., Kamenicky, P., Bernabéu, I., Malchiodi, E., ... Neggers, S. J. C. M. M. (2017). The Effect of the Exon-3-Deleted Growth Hormone Receptor on Pegvisomant-Treated Acromegaly: A Systematic Review and Meta-Analysis. Neuroendocrinology, 105(2), 131-140. https://doi.org/10.1159/000448844

The Effect of the Exon-3-Deleted Growth Hormone Receptor on Pegvisomant-Treated Acromegaly : A Systematic Review and Meta-Analysis. / Franck, Sanne E.; Broer, Linda; Van Der Lely, Aart Jan; Kamenicky, Peter; Bernabéu, Ignacio; Malchiodi, Elena; Delhanty, Patric J.D.; Rivadeneira, Fernando; Neggers, Sebastian J.C.M.M.

In: Neuroendocrinology, Vol. 105, No. 2, 01.08.2017, p. 131-140.

Research output: Contribution to journalReview article

Franck, SE, Broer, L, Van Der Lely, AJ, Kamenicky, P, Bernabéu, I, Malchiodi, E, Delhanty, PJD, Rivadeneira, F & Neggers, SJCMM 2017, 'The Effect of the Exon-3-Deleted Growth Hormone Receptor on Pegvisomant-Treated Acromegaly: A Systematic Review and Meta-Analysis', Neuroendocrinology, vol. 105, no. 2, pp. 131-140. https://doi.org/10.1159/000448844
Franck, Sanne E. ; Broer, Linda ; Van Der Lely, Aart Jan ; Kamenicky, Peter ; Bernabéu, Ignacio ; Malchiodi, Elena ; Delhanty, Patric J.D. ; Rivadeneira, Fernando ; Neggers, Sebastian J.C.M.M. / The Effect of the Exon-3-Deleted Growth Hormone Receptor on Pegvisomant-Treated Acromegaly : A Systematic Review and Meta-Analysis. In: Neuroendocrinology. 2017 ; Vol. 105, No. 2. pp. 131-140.
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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. Design: 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. Conclusion: 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.",
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