Impact of body mass index on growth hormone peak during insulin tolerance test in childrenand adolescents

Background: The insulin tolerance test (ITT) is the gold standard for assessing growth hormone (GH) integrity. A negative relationship between GH peak and body mass index (BMI) standard deviation score (SDS) has been reported, even within the normal BMI range, potentially leading to overdiagnosis of growth hormone deficiency (GHD) in overweight and obese children. In this context, BMI SDS-specific cutoffs for GH stimulation tests have been proposed by Abawi et al. Methods: This retrospective study analyzed ITTs (regular insulin 0. 1 IU/kg intravenously) performed at the Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy, between January 1, 2019, and December 31, 2024. ITTs were conducted to confirm GHD after a blunted response to the arginine stimulation test. Adequate hypoglycemia (<50% decrease in basal glucose or <40 mg/dL) was achieved in 157 of 180 tests. Clinical data and GH responses were analyzed. Results: The cohort had a median age of 12. 3 years (IQR: 10.5–13.8) and a BMI SDS of -0.86 (-1.57–0. 27). GH peak negatively correlated with BMI SDS (Spearman’s r = -0. 311, p <.001), while positive correlations were observed with baseline GH (r=0.536, p<.001) and IGF-1 SDS (r=0.176, p=. 028). Multivariate analysis identified lower BMI SDS (p=. 007) and higher baseline GH (p<. 001) as significant predictors of GH peak, with a moderate overall model fit (R2=0.490). Among the 16 overweight (BMI SDS: 1–2) and 2 obese (BMI SDS >2) individuals, all exhibited pathological GH peaks (<8 ng/mL; median: 1. 5 ng/mL [IQR: 0.75–2.80]). This remained true when applying BMI-adjusted thresholds proposed by Abawi et al. (7. 4 ng/mL for overweight and 6. 8 ng/mL for obese children). Conclusions: This study confirms the significant impact of BMI SDS on GH peak during ITT, highlighting that overweight and obese children are at increased risk of GHD overdiagnosis. Although BMI SDS-adjusted cutoffs could improve diagnostic accuracy and reduce misclassification in children with elevated BMI, in this study, peak GH levels in overweight and obese children were well below even the BMI-adjusted thresholds, supporting a diagnosis of GHD.