Diagnostic utility of IGF-1/IGFBP-3 ratio and the insulin tolerance test in diagnosing growth hormone deficiency.
Integrating the IGF-1/IGFBP-3 molar ratio with the insulin tolerance test may improve the accuracy of diagnosing growth hormone deficiency in children.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study evaluated the diagnostic utility of the IGF-1/IGFBP-3 molar ratio in diagnosing growth hormone deficiency (GHD) in pediatric patients. A total of 225 patients aged 2-18 were analyzed, with confirmed GHD requiring a peak GH < 7 ng/mL. The findings suggest that integrating the molar ratio with the insulin tolerance test (ITT) enhances diagnostic specificity.
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.
Background
Diagnosing Growth Hormone Deficiency (GHD) is complicated due to the pulsatile nature of GH secretion and high false-positive rates in traditional stimulation tests. Previous studies have indicated the potential of various biomarkers in improving diagnostic accuracy. This study aims to assess the IGF-1/IGFBP-3 molar ratio as a complementary diagnostic tool alongside the Insulin Tolerance Test (ITT), which is considered the gold standard.
Methods
This retrospective study analyzed 225 pediatric patients aged 2-18 who were evaluated for short stature between 2015 and 2025. Confirmed GHD was defined by a peak GH < 7 ng/mL across two provocation tests and a positive response to rhGH therapy. Serum levels of IGF-1 and IGFBP-3 were measured to calculate the molar ratio SDS.
Results
The mean IGF-1/IGFBP-3 molar ratio SDS was significantly lower in the GHD group (-1.6 ± 1.1) compared to the non-GHD group (-1.1 ± 1.1). The integration of the molar ratio SDS with ITT improved diagnostic specificity. A threshold of < -1 SDS provided 79.2% sensitivity and 82.7% specificity, while a stricter < -2 SDS threshold increased specificity to 93% with 77% overall accuracy. The overall AUC for the molar ratio SDS was 0.627, with the optimal -2 SDS threshold yielding 45.3% sensitivity and 80.2% specificity.
Interpretation
The findings suggest that the IGF-1/IGFBP-3 molar ratio can enhance the diagnostic accuracy for GHD when used alongside the ITT. While the study reports statistically significant results, the clinical significance of the effect sizes, particularly the sensitivity and specificity at the -2 SDS threshold, may be limited. The retrospective nature and reliance on historical data could introduce confounding factors that affect the reliability of the findings.
Key findings
- Mean IGF-1/IGFBP-3 molar ratio SDS was -1.6 ± 1.1 in GHD vs -1.1 ± 1.1 in non-GHD.
- Threshold of < -1 SDS yielded 79.2% sensitivity and 82.7% specificity.
- Threshold of < -2 SDS elevated specificity to 93% with 77% overall accuracy.
- Overall AUC for the molar ratio SDS was 0.627.
- Optimal -2 SDS threshold yielded 45.3% sensitivity and 80.2% specificity.
Limitations
- Retrospective study design.
- Limited to pediatric patients, affecting generalizability.
- Potential biases from reliance on previously collected data.
- Single-site study may limit external validity.