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.
Acknowledgments
We acknowledge the support from All India Institute of Medical Sciences, New Delhi (grant numbers F.8 -169/ A-169/2012/RS and F.8 – 389/ A-389/2015/RS) and the Indian Council of Medical Research, New Delhi (grant number 3/1/3/JRF-2011/HRD 45 [34683]). We thank Mr. Brijesh Kumar who performed ECLIA for assessment of GH.
Author contributions: AK recruited the subjects, performed the biochemical and genetic workup and drafted the paper; AP helped in recruitment; MK performed biostatistical analysis; NG supervised the IGF-1 measurements; and VJ conceived and supervised the study, critically revised the paper and will act as guarantor. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of report; or in the decision to submit the report for publication.
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