Short and long‐term responsiveness to low dose GH in adult Growth Hormone Deficiency (GHD): role of GH receptor (GHR) polymorphism

Abstract

Purpose

in patients with Growth Hormone Deficiency (GHD), low doses of recombinant human Growth Hormone (rhGH) have a similar or better long‐term clinical effect than higher doses. Pharmacogenetic studies suggest that GH receptor (GHR) polymorphism influences only some metabolic parameters. Nonetheless there is no clear scientific evidence proving the effects of lower rhGH dose regimens on metabolic parameters. The aim of our prospective study is to evaluate the effects of GHR polymorphism in adult GHD patients treated with low rhGH dose during short (6 and 12 months) and long‐term (5 years) follow‐up.

Methods

Sixty‐nine GHD adult patients were studied, before and during treatment with rhGH, using a standardized low‐dose protocol calculated on the basis of body weight (0.01‐0.03 mg/kg/week) and monitored by IGF‐I plasma assay, anthropometric and metabolic parameters. The GHR genotype (flfl, fld3, or d3d3) was determined from peripheral blood.

Results

d3‐GHR carriers showed a more effective short and long‐term response to low rhGH dose in LDL reduction, body composition and blood pressure (homozygous patients only); d3‐GHR homozygosity is related to a significant IGF‐I increase during short‐term follow‐up. Regression analysis demonstrated that rhGH dose, age at diagnosis and GHR genotype are the major determinants of IGF‐I increase at 6 and 12 months of replacement therapy.

Conclusions

the d3d3‐GHR genotype may influence some metabolic effects during short and long‐term follow‐up of low rhGH dose and could be an independent determinant of the increase of IGF‐ I during short‐term follow‐up.

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