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Comparative Analysis of Human Growth Hormone in Serum Using SPRi, Nano-SPRi and ELISA Assays
Published on: January 7, 2016
Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature
Aristeidis Giannakopoulos1, Alexandra Efthymiadou1, Dionisios Chrysis1
1Division of Endocrinology, Department of Pediatrics, Medical School, University of Patras, Patras, Greece.
Insights
Diagnosing growth hormone deficiency (GHD) in children is challenging. While ternary complex components like IGF-I show differences, auxology remains key for diagnosis.
Area of Science:
- Pediatric Endocrinology
- Biomarker Discovery
- Growth Disorders
Background:
- Diagnosing growth hormone deficiency (GHD) in children is complex, as standard tests like IGF-I and GH stimulation tests can be inconclusive.
- Distinguishing GHD from constitutional delay of growth and puberty (CDGP) and other causes of short stature requires reliable diagnostic markers.
Purpose of the Study:
- To evaluate the diagnostic utility of ternary complex components (IGF-I, IGFBP-3, ALS, IGF-I/IGFBP-3 ratio) in differentiating GHD from other causes of short stature in children.
- To assess the discriminatory power of these biomarkers compared to auxological assessment.
Main Methods:
- A longitudinal study of 429 children (0.7-16 years) with short stature was conducted over an average of 9 years.
- Ternary complex components (IGF-I, IGFBP-3, ALS, IGF-I/IGFBP-3 ratio) were measured and analyzed as potential biomarkers at final height.
Main Results:
- All ternary complex components correlated with each other and age. Significant differences in IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio were observed between GHD and normal groups.
- IGF-I and ALS were lower in GHD vs. familial short stature; IGF-I and IGF-I/IGFBP-3 ratio were lower in GHD vs. CDGP.
- Receiver operating curve analysis showed that IGF-I and IGF-I/IGFBP-3 ratio lacked sufficient discriminatory power between GHD and normal/CDGP groups.
Conclusions:
- Despite statistically significant alterations in ternary complex components based on diagnosis, their discriminatory power is insufficient for definitive GHD diagnosis.
- Auxological assessment (growth parameters) remains the primary criterion for diagnosing GHD in children.
- Further research may be needed to identify more robust biomarkers for GHD diagnosis.
Objective:
The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature.
Design:
Boys and girls (n = 429, 0.7-16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis.
Results:
All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups.
Conclusion:
Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.
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