Etiology of short stature in Indian children and an assessment of the growth hormone-insulin-like growth factor axis in children with idiopathic short stature

Abstract

Background Our objectives were to evaluate the etiology of short stature, assess the prevalence of idiopathic short stature (ISS) and assess the growth hormone (GH)-insulin-like growth factor (IGF) axis in children with ISS. Methods A stepwise diagnostic evaluation was done in 394 children aged 4-16 years with short stature. Children with no definitive etiology were labeled as ISS. In these children, baseline IGF-1, IGF binding protein-3 (IGFBP-3) and stimulated IGF-1 after administration of GH for 4 days were measured. Results Hypothyroidism (in 18.1%) and ISS (in 15.5%) were the commonest causes of short stature. In children with ISS (n=61), the mean baseline and stimulated IGF-1 standard deviation scores (SDSs) were -1.2±1.0 and -0.3±1.4, respectively, with levels below -2 SDS in 13 (21%) and six (10%) children, respectively. In 33 (54%) of the ISS patients, response to GH was suboptimal (increment in the IGF-1 level <40%). There was no difference in the mean peak GH, IGFBP-3 and baseline and stimulated IGF-1 levels between children with familial and non-familial ISS. A significant positive correlation of height SDS with baseline IGF-1 SDS (r=0.28, p=0.026), stimulated IGF-1 SDS (r=0.32, p=0.010) and ΔIGF-1 SDS (r=0.26, p=0.036) was observed in children with ISS. Conclusions Hypothyroidism and ISS were the commonest etiologies for short stature. The baseline IGF-1 was below -2 SDS in 21% and the increment after GH stimulation was suboptimal in 54% of children, indicating that a substantial proportion of children with ISS had an impaired GH-IGF axis.

Keywords: IGF-1 generation test; familial short stature; growth hormone; height velocity; non-familial short stature.