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

Abstract

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. 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. 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). 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.