GH Response to Glucagon in Transition: Role of BMI and Etiology in Childhood-Onset GH Deficiency

Context The glucagon stimulation test (GST) is increasingly used as an alternative to the insulin tolerance test for diagnosing persistent growth hormone (GH) deficiency during transition, though its accuracy and appropriate cutoff values are still uncertain. Objective To investigate the GH response to GST in transitional-age patients with childhood-onset GHD (CO-GHD), with a focus on the influence of BMI and underlying etiology. Patients and Methods A total of 180 patients with CO-GHD (median age 17.39 years) underwent GST. They were grouped based on the number of pituitary deficiencies and MRI findings into I-GHD (isolated, n=80), OM-GHD (1–2 deficiencies with congenital or acquired anomalies, n=63), and OS-GHD (≥3 deficiencies with complex CNS abnormalities, n=37). Additionally, patients were classified by BMI as normal weight, overweight, or obesity, according to age-appropriate BMI criteria. Childhood cancer survivors (CCS) accounted for 42% of the cohort. Results Peak GH response to GST showed a significant inverse association with the severity of pituitary dysfunction (p < 0.001) and an inverse correlation with BMI SDS (ρ = –0.46, p < 0.001). However, adjusting by disease group strongly reduced the impact of BMI on the GST response. When stratified by etiology or CCS status, GH peaks were primarily influenced by hypothalamic-pituitary damage with BMI showing a minimal effect. Conclusion The GST provides valuable insights into GH deficiency in transitional-age patients with CO-GHD. GH response is primarily influenced by the severity of pituitary dysfunction, with BMI playing a minimal role once adjusted for etiology.