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

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.

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.

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.

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.