Growth Hormone/IGF-I Axis and Growth Hormone Receptor Mutations in Idiopathic Short Stature

Abstract

Background/Aims: It was hypothesized that some children with idiopathic short stature (ISS) may have partial insensitivity to growth hormone (GH). In this study analysis of the GH/IGF-I axis as well as GH receptor (GHR) gene was done in children with ISS to determine the possible underlying factor(s) to their short stature. Methods: Forty-eight patients with a diagnosis of ISS were studied; 33 boys and 15 girls aged 13.6 ± 3.7 years. Molecular analysis of the GHR was performed and GH sensitivity was tested by the IGF-I generation test. Results: Basal IGF-I levels were <–2 SD in 22.9%, and 53.5% showed an IGF-I response below 40% (0–38%) to GH stimulation. GH-binding protein (GHBP) levels were below the normative mean in almost all patients. Mutations in the region of the GHR gene that codes for the extracellular domain of the receptor were found in 15.5%; one newly described mutation was recorded. Conclusion: With the possible exception of the novel G62V mutation, functional studies of the other 2 heterozygous mutations found in 6 of our patients are needed in order to prove their impact on short stature.