Obesity-Related Changes in Growth Hormone Stimulation Test Performance Under Pediatric Growth Hormone Deficiency

TL;DR

Obesity affects the accuracy of growth hormone deficiency tests in children, but a new two-step diagnostic approach improves test reliability.

Contribution

A structured two-step diagnostic algorithm integrating IGF-1 and growth velocity improves GHD diagnosis in obese children.

Findings

Obesity reduces the specificity of clonidine stimulation tests for growth hormone deficiency.

A two-step algorithm using low GH thresholds and IGF-1/GV improves diagnostic accuracy in obese children.

False-positive diagnoses increase in obese children using fixed GH cutoffs.

Abstract

What are the main findings?
Obesity substantially impairs the diagnostic specificity of the clonidine stimulation test, leading to a marked increase in false-positive growth hormone deficiency diagnoses.A structured two-step algorithm integrating low GH peak thresholds with IGF-1 SDS and growth velocity restores diagnostic discrimination and significantly reduces obesity-related misclassification.

Obesity substantially impairs the diagnostic specificity of the clonidine stimulation test, leading to a marked increase in false-positive growth hormone deficiency diagnoses.

A structured two-step algorithm integrating low GH peak thresholds with IGF-1 SDS and growth velocity restores diagnostic discrimination and significantly reduces obesity-related misclassification.

What are the implications of the main findings?
Fixed GH cutoffs applied to clonidine stimulation testing are insufficient in children with obesity and risk inappropriate growth hormone treatment.A BMI-aware, auxology-integrated diagnostic strategy represents a more accurate and clinically sustainable framework for evaluating suspected GHD in contemporary pediatric populations.

Fixed GH cutoffs applied to clonidine stimulation testing are insufficient in children with obesity and risk inappropriate growth hormone treatment.

A BMI-aware, auxology-integrated diagnostic strategy represents a more accurate and clinically sustainable framework for evaluating suspected GHD in contemporary pediatric populations.

Background/Objectives: The objective of this study is to determine the extent to which obesity alters the diagnostic reliability of the clonidine stimulation test (CST) for growth hormone deficiency (GHD) and whether incorporating insulin-like growth factor 1 (IGF-1) and the annual growth velocity standard deviation score (GV SDS) improves diagnostic precision. Methods: This retrospective study included 101 children evaluated for short stature using the clonidine stimulation test, with serum GH concentrations determined by a two-site, solid-phase, enzyme-labeled chemiluminescent immunometric assay (Immulite 2000 XPi, Siemens Healthcare Diagnostics, USA). Diagnostic performance was compared between overweight/obese (n = 47) and normal-weight (n = 54) groups. A two-step algorithm was evaluated: Step 1 applied a GH peak threshold of <5 ng/mL; Step 2 integrated IGF-1 SDS < −1.5 and annual GV SDS < −2.0 among children with subthreshold GH responses. Results: The median GH peak was significantly lower in overweight/obese children (4.5 [IQR 2.0–7.4] vs. 8.2 [5.1–11.5] ng/mL; p = 0.043). Although sensitivity remained comparable (82.6% vs. 90.5%; p = 0.666), elevated BMI markedly reduced specificity (50.0% vs. 84.8%; p = 0.008) and overall accuracy (66.0% vs. 87.0%; p = 0.017). Overweight/obese children demonstrated a higher proportion of false-positive CST results than non-obese children (25.5% vs. 9.3%). Among obese children with a GH peak of <5 ng/mL (n = 31), Step 2, which integrates IGF-1 and GV, improved specificity from 50% to 75% and the positive predictive value from 61.3% to 84.2%, correctly reclassifying 9 of 12 children without GHD who would otherwise have been misdiagnosed based on CST alone. Conclusions: Fixed GH cutoffs may lead to the misclassification of GHD in children with elevated BMI. Obesity significantly reduces the specificity and diagnostic accuracy of CST, increasing false-positive results. A two-step approach integrating IGF-1 and GV improves diagnostic precision and helps to differentiate true GHD from obesity-related GH suppression.

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