Endocrine Abstracts (2009) 20 P550

Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly

Antonio Bianchi1, Gherardo Mazziotti2, Laura Tilaro1, Vincenzo Cimino1, Teresa Porcelli1, Marilda Mormando1, Linda Tartaglione1, Alfredo Pontecorvi1, Andrea Giustina2 & Laura De Marinis1


1Department of Endocrinology, School of Medicine, Catholic University, Rome, Italy; 2Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy.


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.