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Auxology-based cut-off values for biochemical testing of GH secretion in childhood
G Binder1, E Huller, G Blumenstock
1University-Children's Hospital, Pediatric Endocrinology, Tuebingen, Germany. gunnel.hellgren@vgregion.se
Insights
This study defines new growth hormone (GH) cut-offs for diagnosing childhood GH deficiency (GHD) using auxology, improving diagnostic accuracy and predicting GH therapy response. The findings offer a rational approach to replace arbitrary GH testing thresholds.
Area of Science:
- Pediatric Endocrinology
- Growth Hormone Research
- Diagnostic Criteria Development
Background:
- Childhood growth hormone deficiency (GHD) diagnosis relies on arbitrary growth hormone (GH) test cut-offs.
- Existing diagnostic criteria may lack precision, potentially impacting treatment decisions and outcomes.
Purpose of the Study:
- To establish evidence-based GH cut-offs for diagnosing childhood GHD using auxological parameters.
- To improve the accuracy of GHD diagnosis and treatment response prediction.
Main Methods:
- Retrospective analysis of 349 children diagnosed with GHD, with 52 meeting strict auxological inclusion criteria.
- Utilized receiver operating characteristic (ROC) analysis to determine optimal GH cut-offs for arginine and spontaneous nighttime secretion.
- Compared new cut-offs with historical arbitrary thresholds and assessed impact on GH therapy responsiveness.
Main Results:
- Optimal peak GH cut-offs were identified as 6.6 μg/L for arginine tests (AUC=0.83) and 7.3 μg/L for spontaneous nighttime secretion (AUC=0.93).
- Children diagnosed with GHD using higher, arbitrary cut-offs showed reduced responsiveness to GH therapy (P=0.007).
Conclusions:
- A novel, auxology-based approach provides rational GH cut-offs for diagnosing childhood GHD.
- These new criteria enhance diagnostic precision and offer a more reliable prediction of GH therapy efficacy.
Objective:
The diagnosis of GH deficiency (GHD) in childhood requires GH tests with arbitrary cut-offs. We aimed to define GH cut-offs based on auxology.
Design:
From a total of 349 children diagnosed with GHD between 1985 and 2005 at our hospital, we excluded all children who had additional characteristics likely to interfere with growth velocity. Age at start of therapy was defined as 4 to 8/9 years (girls/boys). Auxological inclusion criteria were pathological growth velocity, height at start of therapy >1.5 SD below the target, and efficient catch-up growth during GH therapy. Basal IGF-I/IGFBP-3, GH response to arginine and spontaneous GH secretion at night had been measured by the same polyclonal RIA. The reference was a group of 108 normally growing age-matched children with Turner syndrome or born small for gestational age tested during the same time period.
Results:
We identified 52 children with GHD who fulfilled the inclusion criteria. ROC analysis showed the best diagnostic accuracy at a peak GH cut-off for arginine of 6.6 μg/L (sensitivity, 84.3%; specificity, 75.5%; AUC=0.83) and at a peak GH cut-off during spontaneous secretion at night of 7.3 μg/L (sensitivity, 96.8%; specificity, 82.4%; AUC=0.93). Our arbitrarily defined GH cut-offs had been higher. Children diagnosed with GHD in the past with GH test values above the new cut-offs were less responsive to GH therapy (P=0.007).
Conclusions:
Here we provide a new rational approach which allows the substitution of arbitrarily defined GH cut-offs by those based on auxology.
