Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly

Clinical trials have demonstrated that pegvisomant therapy is highly efficacious, normalizing serum IGF-I levels in the majority of patients with acromegaly. Multiple factors could influence the dose of pegvisomant required to normalize IGF-I, that ranging from 10 to 40 mg/day. However, the determinants of this variability are unknown and, to date, there is no specific recommendation to adjust the dose to the type of patient. Lack of exon 3 of the Growth Hormone receptor (d3-GHR) has been associated with increased responsiveness to GH therapy and with a more morbid acromegalic clinical and biochemical picture. Aim of our study was to assess whether the presence of polymorphism of GH receptor may have a role in predictive dose regimen and responsivity to pegvisomant in acromegaly. We studied a cohort of 19 acromegalic patients with active disease after unsuccessful neurosurgery and somatostatin analogs therapy. All patients started treatment with pegvisomant at 10 mg daily and then increased during a 12-months follow-up until normalize IGF-I levels. The genotype of the GH receptor was determined from peripheral blood. The patients carriers of d3-GHR genotype required a significant lower dose and shorter treatment time to normalize IGF-I. In conclusion, we demonstrated that in acromegaly the GHR genotype could be useful in predicting dose and individual response to pegvisomant in acromegaly.