GH Response to Glucagon in Transition: Role of Body Mass Index and Etiology in Childhood-onset GH Deficiency

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CONTEXT: The glucagon stimulation test (GST) is increasingly used as an alternative to the insulin tolerance test for diagnosing persistent GH deficiency (GHD) 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 body mass index (BMI) and the 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 magnetic resonance imaging findings into isolated GHD (n = 80), organic moderate GHD (1-2 deficiencies with congenital or acquired anomalies, n = 63), and organic severe GHD (≥3 deficiencies with complex central nervous system 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 < .001) and an inverse correlation with BMI SD score (ρ = -0.46, P < .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.

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