Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly

Background Sensitivity to pegvisomant therapy is highly variable in patients with acromegaly but determinants of this variability are still unknown. Lack of exon 3 (d3-) of the growth hormone (GH) receptor (GHR) has been associated with increased biological activity of GH. Objective To assess whether the presence of d3-GHR haplotype may have a role in predicting dose regimen and response to pegvisomant in acromegaly. Design Case series. Setting Institutional referral center at a tertiary care hospital. Patients Ninenteen acromegalic patients with active disease after unsuccessful neurosurgery and somatostatin analog therapy. Measurements before and 1, 3, 6 and 12 months after treatment with pegvisomant, IGF-I; GH receptor genotype, determined from peripheral blood by polymerase chain reaction. All patients started treatment with pegvisomant at 10 mg/daily and then increased the dose, according to a fixed schedule, during a 12-month follow-up until normalization of IGF-I levels. Results d3-GHR patients required a significant lower dose of pegvisomant and shorter treatment time to normalize IGF-I. Conclusion the GHR genotype could be useful in predicting dose and individual response to pegvisomant in acromegaly.