The exon 3-deleted growth hormone receptor is associated with better response to pegvisomant therapy in acromegaly.

Context: The deletion of exon 3 in the GH receptor (GHR) has been associated with a different biochemical picture and response to therapy in acromegaly.

Objective: The aim of the study was to determine whether or not the GHR genotype influences the efficacy of pegvisomant treatment.

Design And Setting: A cross-sectional study was conducted in six Spanish university hospitals.

Patients: Forty-four acromegalic patients with active disease and resistance to somatostatin analogs participated in the study.

Results: The prevalence of the full-length GHR and the exon 3-deleted GHR homozygous and heterozygous genotypes was 41, 2, and 57%, respectively. There were no differences in IGF-I or GH pre-pegvisomant levels related to GHR genotype. The exon 3-deleted patients required approximately 20% lower doses of pegvisomant per kilogram of weight (28 +/- 11 compared to 22 +/- 7 mg per kg of weight; P = 0.033) to normalize IGF-I. A stepwise multivariate linear regression analysis (R(2) = 0.27; P = 0.003) identified male gender (beta = -0.79; P = 0.03) and d3-GHR genotype (beta = -0.64; P = 0.007) as the only significant predictors of the dose of pegvisomant per kilogram of weight. In addition, d3-GHR carriers required fewer months for IGF-I normalization (P < 0.01). A stepwise multivariate linear regression analysis (R(2) = 0.40; P = 0.001) revealed that the only significant predictor of the time to IGF-I normalization was the dose of pegvisomant per kilogram of weight (beta = 0.451; P = 0.001).

Conclusions: The exon 3 deletion in the GHR predicts an improved response to pegvisomant therapy in acromegaly.