Objective: Recombinant human growth hormone (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 year (n=99) and in a subset during 5 years (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 wildtype alleles (56%), whereas 38 patients (38%) had one allele and 6 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 to those with two wildtype alleles (at an identical mean dose of rhGH). The decrease in total cholesterol and LDL cholesterol was lower in the group bearing at least one d3GHR allele, whereas the increase in HDL cholesterol was higher compared to patients with the wildtype 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 of long-term, rhGH replacement in adults with GHD.