The Effect of Body Mass Index on Peak Growth Hormone Response During Stimulation Testing: A Retrospective Analysis

Background: Growth hormone (GH) stimulation testing remains the diagnostic gold standard for GH deficiency (GHD), but body mass index (BMI) inversely influences peak GH levels, creating a risk of overdiagnosis. We evaluated the association between BMI standard deviation score (SDS) and peak GH response in children undergoing diagnostic work-up for suspected GHD. Methods: This is a retrospective single-center study of 298 children (55.4% male, mean age 9.5 ± 2.9 years) evaluated for growth failure with arginine or clonidine stimulation testing. GHD was confirmed in 114 patients (38.3%). Multivariable linear and logistic regression models evaluated associations after adjustment for age, sex, and pubertal status. Results: BMI SDS negatively correlated with peak GH levels in the overall cohort (r = -0.299, p < 0.001) and in GHD patients (r = -0.322, p < 0.001), but not in non-GHD controls (r = -0.102, p = 0.167; Fisher's z p = 0.050). On multivariable analysis, each 1-SDS increase in BMI SDS was independently associated with a 1.63 ng/mL reduction in peak GH (β = -1.63, 95% CI -2.20 to -1.07; p < 0.001) and 2.10-fold higher odds of GHD diagnosis (OR 2.10, 95% CI 1.60-2.74; p < 0.001). Across BMI SDS quartiles (Q1 to Q4), mean peak GH progressively decreased from 11.14 to 6.93 ng/mL (p < 0.0001), while GHD prevalence increased from 22.4% to 62.7% (p < 0.0001). Conclusions: BMI SDS significantly blunts peak GH response and increases the likelihood of a GHD diagnosis. This inverse relationship was evident primarily in children with confirmed GHD, suggesting that adiposity predominantly impairs an already compromised somatotropic axis. Adiposity should be accounted for when interpreting GH stimulation tests.