Validation of Peak Growth Hormone Levels After Clonidine and Glucagon Stimulation Tests in Children With Severe Short Stature

Introduction This study evaluated the concordance and temporal dynamics of growth hormone (GH) responses during the clonidine stimulation test (CST) and glucagon stimulation test (GST) in children being evaluated for growth hormone deficiency (GHD), and identified optimal sampling time points that may allow protocol simplification without compromising diagnostic agreement. Methods This prospective study included 55 children who were subjected to CST and GST at a one-week interval. Blood samples for GH were taken at different time intervals following each provocative test per standard protocols. GH levels were estimated by the electrochemiluminescence immunoassay (ECLIA) method. A peak GH level of less than 8 ng/mL was considered diagnostic of GHD. Results Among 55 children, 41 were diagnosed with GHD and 14 with idiopathic short stature (ISS). Overall, peak GH levels were noted at 0, 60, and 90 minutes after CST and 0, 120, and 180 minutes after GST in more than 98% of the study cohort. The sensitivity of CST and GST in diagnosing GHD was 87.8% and 90.2%, and the specificity was 85.5% and 100%, respectively. The combined provocative tests (CST and GST) had an area under the curve (AUC) of 1.000, outperforming the individual tests, which had an AUC of 0.914 for CST and 0.987 for GST, to diagnose GHD and ISS. Conclusions CST and GST show high concordance in the evaluation of GHD using modern ECLIA-based assays, with GST demonstrating relatively higher specificity. Optimization of sampling time points permits protocol simplification without compromising diagnostic agreement, improving clinical utility.