ECE2010 Oral Communications Pituitary (6 abstracts)
Influence of the d3-GH receptor polymorphism on the metabolic and biochemical phenotype of GH deficient adults at baseline and during short- and long-term rhGH replacement therapy
Claudia Giavoli 1 , Emanuele Ferrante 1 , Eriselda Profka 1 , Luca Olgiati 1 , Silvia Bergamaschi 1 , Cristina L Ronchi 1 , Elisa Verrua 1 , Marcello Filopanti 1 , Elena Passeri 2 , Laura Montefusco 3 , Andrea G Lania 1 , Sabrina Corbetta 2 , Maura Arosio 3 , Bruno Ambrosi 2 , Anna Spada 1 & Paolo Beck Peccoz 1
1Endocrinology and Diabetology Unit, Department of Medical Sciences, University of Milan, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy; 2Endocrinology Unit, Department of Medical and Surgical Sciences, University of Milan, Policlinico San Donato IRCCS, Milan, Italy; 3Unit of Endocrinology, University of Milan, Ospedale San Giuseppe Milan, Milan, Italy.
A common polymorphic variant of the GH receptor (exon-3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some, but not all, GH deficient (GHD) and non-GHD patients. Aim of this study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of short- and long-term rhGH therapy, with particular focus on glucose homeostasis (1 year: n=100 and 5 years: n=50). Effects of rhGH on IGF1 serum levels, body composition (BF%), BMI, lipid profile and glucose homeostasis (fasting insulin and glucose, insulin sensitivity determined by HOMA and QUICKI) were evaluated according to the presence or absence of the d3GHR variant. Forty-eight percent of patients had two wild-type alleles (fl/fl), 45% one allele and 7% two alleles encoding the d3GHR isoform. Patients bearing at least one d3 allele (d3/d3 or d3/fl) were grouped together and indicated as d3GHR. The different genotype did not influence the phenotype of GHD adults at baseline. Short-term rhGH determined normalization of IGF1 levels, decrease in BF% and transient worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in HDL cholesterol occurred only in the d3GHR group (from 50±16 to 55±18 mg/dl, P<0.05). Concerning long-term effects, normalization of IGF1 levels and decrease of BF% maintained after 5 years. Insulin sensitivity restored to baseline values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. Moreover, both after 1 and 5 years, proportion of subjects with impaired glucose tolerance, similar in the 2 genotype-groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group a long-term significant reduction of total and LDL cholesterol was also observed (from 208±50 to 188±41 mg/dl and from 136±35 to 105±53, respectively, P<0.05). In conclusion, present results seem to support the view that functional difference of d3GHR may influence at least some of the metabolic effects of rhGH in GHD adults.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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