Diagnostic utility of IGF-1/IGFBP-3 ratio and the insulin tolerance test in diagnosing growth hormone deficiency.

Abstract

Purpose Diagnosing Growth Hormone Deficiency (GHD) is challenging due to pulsatile GH secretion and high false-positive rates in traditional stimulation tests. This study evaluates the diagnostic utility of the IGF-1/IGFBP-3 molar ratio as a complementary tool to the gold-standard Insulin Tolerance Test (ITT). Methods A retrospective study analyzed 225 pediatric patients (aged 2-18) evaluated for short stature between 2015 and 2025. Confirmed GHD required a peak GH < 7 ng/mL across two provocation tests and a positive response to rhGH therapy. Serum IGF-1 and IGFBP-3 levels were quantified to calculate the molar ratio standard deviation score (SDS). Results The cohort included 82 GHD and 143 non-GHD subjects. The mean IGF-1/IGFBP-3 molar ratio SDS was significantly lower in the GHD group compared to non-GHD (-1.6 ± 1.1) vs (-1.1 ± 1.1). Integrating the molar ratio SDS with ITT significantly enhanced diagnostic specificity. A threshold of < -1 SDS yielded 79.2% sensitivity and 82.7% specificity. A stricter < -2 SDS threshold elevated specificity to 93% (77% overall accuracy). In standalone ROC analysis, the overall AUC for the molar ratio SDS was 0.627, with the optimal -2 SDS threshold yielding a sensitivity of 45.3% and a specificity of 80.2%. Conclusion Stratifying the ITT with the IGF-1/IGFBP-3 molar ratio mitigates GHD over-diagnosis. The < -2 SDS threshold's high specificity ensures hormone replacement therapy is accurately targeted, advancing precision medicine for pediatric growth disorders.