Influence of the exon 3 deletion of GH receptor and IGF-I level at diagnosis on the efficacy and safety of treatment with somatotropin in adults with GH deficiency.

PURPOSE: The treatment of adults with GH deficiency (GHD) with human recombinant growth hormone has interindividual variability and several factors influence it. The aims of this study were : 1-to analyze the GH receptor (GHR) genotype in terms of exon 3 deletion GHR (d3-GHR) in adults with GHD; 2-to assess the effects of d3-GHR on initial IGF-I levels; 3-to evaluate whether d3-GHR and/or initial IGF-I levels were associated with adverse effects and/or treatment discontinuation.
METHODS: Forty-four adult patients with GHD were included. Demographic, clinical and biochemical characteristics were retrospectively evaluated at baseline and 6 months, 1 and 3 years after the initiation of treatment. d3-GHR was analyzed in 35 patients.
RESULTS: 37.1% of patients were d3-GHR carriers (31.4% heterozygous, 5.7% homozygous). IGF-I at baseline was low in 64% of patients and was not related to d3-GHR status. There was no association between the d3-GHR allele and baseline IGF-I (p = 0.14). Although adverse events were more frequent in the d3-GHR carriers (30.7 vs. 18.2% in fl/fl) and in patients with normal IGF-I levels at diagnosis (43.7 vs. 17.8% in patients with low IGF-I levels), this association was not statistically significant. d3-GHR status was not related to the incidence of adverse events (p = 0.4) or treatment discontinuation (p = 0.47). Baseline IGF-I levels were neither associated with adverse events (p = 0.08) nor treatment discontinuation (p = 0.75).
CONCLUSIONS: The d3-GHR allele was not related to baseline levels of IGF-I. Neither d3-GHR nor baseline IGF-I level was related to adverse events or treatment discontinuation.