OBJECTIVE: Recombinant human GH (rhGH) replacement in adults is aimed at improving signs and symptoms of the adult GH deficiency (GHD) syndrome. In children, a common polymorphism of the GH receptor (exon-3 deletion, d3GHR) increases the response to rhGH replacement. The aim of this study was to assess the effects of this polymorphism on the response to rhGH replacement in adults. DESIGN: Prospective intervention with rhGH during 1 yr (n = 99) and in a subset during 5 yr (n = 53). PATIENTS AND METHODS: The presence of the d3GHR variant was established in GHD patients and linked to short-term and long-term effects of rhGH replacement on IGF-I, lipid metabolism, anthropometric parameters, and bone mineral density. RESULTS: Fifty-five patients had two wild-type alleles (56%), whereas 38 patients (38%) had one allele and six patients (6%) had two alleles coding the d3GHR isoform. During short-term rhGH replacement, the increase in IGF-I was higher in patients bearing at least one d3GHR allele, compared with those with two wild-type alleles (at an identical mean dose of rhGH). The decrease in total cholesterol and low-density lipoprotein cholesterol was lower in the group bearing at least one d3GHR allele, whereas the increase in high-density lipoprotein cholesterol was higher, compared with patients with the wild-type genotype. In contrast, these differential responses of GHR genotype could not be demonstrated during long-term rhGH replacement. CONCLUSION: The d3GHR genotype contributes, at least for some parameters, to the interindividual differences in efficacy of short-term, but not long-term, rhGH replacement in adults with GHD.
OBJECTIVE: Recombinant human GH (rhGH) replacement in adults is aimed at improving signs and symptoms of the adult GH deficiency (GHD) syndrome. In children, a common polymorphism of the GH receptor (exon-3 deletion, d3GHR) increases the response to rhGH replacement. The aim of this study was to assess the effects of this polymorphism on the response to rhGH replacement in adults. DESIGN: Prospective intervention with rhGH during 1 yr (n = 99) and in a subset during 5 yr (n = 53). PATIENTS AND METHODS: The presence of the d3GHR variant was established in GHD patients and linked to short-term and long-term effects of rhGH replacement on IGF-I, lipid metabolism, anthropometric parameters, and bone mineral density. RESULTS: Fifty-five patients had two wild-type alleles (56%), whereas 38 patients (38%) had one allele and six patients (6%) had two alleles coding the d3GHR isoform. During short-term rhGH replacement, the increase in IGF-I was higher in patients bearing at least one d3GHR allele, compared with those with two wild-type alleles (at an identical mean dose of rhGH). The decrease in total cholesterol and low-density lipoprotein cholesterol was lower in the group bearing at least one d3GHR allele, whereas the increase in high-density lipoprotein cholesterol was higher, compared with patients with the wild-type genotype. In contrast, these differential responses of GHR genotype could not be demonstrated during long-term rhGH replacement. CONCLUSION: The d3GHR genotype contributes, at least for some parameters, to the interindividual differences in efficacy of short-term, but not long-term, rhGH replacement in adults with GHD.
Authors: L Drori-Herishanu; M Lodish; S Verma; E Bimpaki; M F Keil; A Horvath; C A Stratakis Journal: Horm Metab Res Date: 2009-12-09 Impact factor: 2.936
Authors: Felipe Albuquerque Marques; Túlio Cesar Lins; Ricardo Moreno Lima; Rômulo Maia Carlos Fonseca; Nanci Maria de França; Ricardo Jacó de Oliveira; Maria Teresinha de Oliveira Cardoso; Rinaldo Wellerson Pereira; Robert Pogue Journal: Endocrine Date: 2013-06-28 Impact factor: 3.633