Growth hormone receptor variants and response to pegvisomant in monotherapy or in combination with somatostatin analogs in acromegalic patients: a multicenter study

J Clin Endocrinol Metab. 2012 Feb;97(2):E165-72. doi: 10.1210/jc.2011-1769. Epub 2011 Dec 7.


Context: The influence of full-length GH receptor (GHR) and exon 3-deleted GHR (d3GHR) on responsiveness to pegvisomant (PEG-V) in acromegalic patients is uncertain.

Objective: The aim of the study was to assess the distribution of GHR genotypes in a large series of patients on PEG-V therapy and their influence on treatment efficacy and adverse effects.

Design and setting: A cross-sectional multicenter pharmacogenetic study was conducted in 16 Italian endocrinology centers of major universities and tertiary care hospitals.

Patients: The study included 127 acromegalic patients enrolled from 2009 to 2010 not cured by previous surgery, radiotherapy, and long-acting somatostatin (SST) analogs, treated with PEG-V.

Intervention and main outcome measure: Sixty-three of 127 patients received combined PEG-V + SST analog therapy. Clinical and hormonal data at diagnosis and before and during PEG-V therapy were inserted in a database. GHR exon 3 deletion and other polymorphisms were genotyped by the coordinator center. Differences in PEG-V dosage required for IGF-I normalization and occurrence of adverse effects between carriers and noncarriers of GHR variants were evaluated.

Results: d3GHR variants were not in Hardy-Weinberg equilibrium (P = 0.008). No association of these variants with PEG-V dose required for IGF-I normalization, adverse effects occurrence, and tumor regrowth was found in patients on PEG-V and on PEG-V + SST analog treatment. Similar data were obtained considering the GHR variant rs6180.

Conclusions: This study did not confirm a better response of d3GHR to PEG-V treatment in acromegaly. Other studies are needed to determine whether deviation from Hardy-Weinberg equilibrium may indicate an association of d3GHR genotype with poor response to usual treatments.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / drug therapy*
  • Acromegaly / etiology
  • Acromegaly / genetics
  • Adenoma / complications
  • Adenoma / drug therapy
  • Adenoma / genetics
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Growth Hormone-Secreting Pituitary Adenoma / complications
  • Growth Hormone-Secreting Pituitary Adenoma / drug therapy
  • Growth Hormone-Secreting Pituitary Adenoma / genetics
  • Human Growth Hormone / administration & dosage
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / analogs & derivatives*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Receptors, Somatotropin / genetics*
  • Somatostatin / administration & dosage
  • Somatostatin / adverse effects
  • Somatostatin / analogs & derivatives*


  • Receptors, Somatotropin
  • Human Growth Hormone
  • Somatostatin
  • pegvisomant