Value of IGF-1 for childhood growth hormone deficiency

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.

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Publication Details

Journal
Endocrine and Metabolic Science
Published
2026-07-23
DOI
https://doi.org/10.1016/j.endmts.2026.100322
Primary Topic
Growth Hormone and Insulin-like Growth Factors
Type
article
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article

Value of IGF-1 for childhood growth hormone deficiency

Peter Kamerman, David Segal, Kerry Marran, Daniel Saksenberg
Endocrine and Metabolic Science
Growth Hormone and Insulin-like Growth Factors
article

Value of IGF-1 for childhood growth hormone deficiency

Peter Kamerman, David Segal, Kerry Marran, Daniel Saksenberg
article en

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.

Endocrine and Metabolic ScienceVol. 22
University of the Witwatersrand (ZA), Johannesburg Hospital (ZA), Yale University (US), Wits University Donald Gordon Medical Centre (ZA)
Zero hunger
Openalex Percentile: Top 9%
Growth Hormone and Insulin-like Growth Factors
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