Value of IGF-1 for childhood growth hormone deficiency

Abstract

Introduction Growth hormone deficiency (GHD) is an important cause of short stature, but GH stimulation tests are costly, time-consuming, and imperfect. Insulin-like growth factor-1 (IGF-1) has been proposed as a potential screening or diagnostic tool, but its accuracy is uncertain. Methods We performed a retrospective review of 431 children referred for evaluation of growth disorders between 2010 and 2020. 357 patients were included in the analysis. IGF-1 standard deviation scores (SDS), normalised for age and sex, were compared with peak GH concentrations. GHD was defined using four GH cut-offs (<3, <5, <7, and <10 ng/mL). IGF-1 SDS was evaluated using quantile regression and 2 × 2 confusion matrices to derive sensitivity, specificity, accuracy, the no-information rate (NIR), and Cohen's kappa as a chance-corrected agreement statistic, as well as ROC curve analysis. Results Peak GH concentration showed a statistically significant but very weak association with IGF-1 SDS (0.04 SDS per 1 ng/mL GH; p = 0.002). Median IGF-1 SDS did not differ materially between GHD and non-GHD groups at any GH cut-off. Sensitivity was low across GH thresholds, ranging from 18.8% to 44.1%, whereas specificity remained relatively high, ranging from 86.7% to 88.1, and accuracy did not significantly exceed the NIR at any GH threshold. Agreement between IGF-1 and GH-defined GHD was low (Cohen's kappa 0.055–0.234). Conclusion IGF-1 had poor sensitivity and limited overall diagnostic accuracy for predicting GHD across all GH cut-offs, despite relatively high specificity. Our findings support the view that IGF-1 should be interpreted as an adjunct to clinical and auxological assessment and dynamic testing, rather than as a stand-alone screening test for paediatric GHD.