A-164 Glucagon Stimulation Test in the Evaluation of GH Deficiency in Children: Peak Time, Glycemic Nadir, and Diagnostic Cutoffs

Abstract

The glucagon stimulation test (GST) is widely used to assess growth hormone (GH) secretion in children with suspected GH deficiency (GHD), particularly when the insulin tolerance test is contraindicated. However, uncertainties persist regarding late hypoglycemia, GH peak timing, the feasibility of shorter protocols, and variability in diagnostic cutoffs (5–7 ng/mL). This study evaluated GH peak timing, magnitude, and glycemic patterns during the GST, exploring their relationship with diagnostic cutoffs and test duration. This retrospective observational study was conducted at a clinical laboratory in Fortaleza, Brazil, including children with suspected GHD who underwent the GST between 2021 and 2024. Clinical and hormonal data were extracted from electronic medical records, anonymized, and analyzed under an ethics committee-approved protocol. Children with complete GST records were included; those with conditions affecting GH secretion or incomplete data were excluded. Primary outcomes were baseline and peak stimulated GH (GHmax). Peak timing was defined as time-to-GHmax. Anthropometric status was characterized by height Z-score < -2 versus > or = -2 and BMI Z-score < or = +1 versus > +1. GH response was evaluated using peak thresholds of 5 and 7 ng/mL. Serum GH was measured by chemiluminescent immunoassay. Hypoglycemia was defined as glucose < 70 mg/dL and severe hypoglycemia as < 40 mg/dL, assessed by plasma or capillary point-of-care testing. Fifty-one children were evaluated (57% girls; mean age 6.11 ± 2.96 years); three were excluded for incomplete data. Among 48 children, 88% reached GH peak within 120 minutes, most frequently at 120 min (69%). Plasma glucose was available in 11 cases; capillary methods were used in the remainder, reflecting variability in clinical practice. Among those with plasma assessments, 73% had a glycemic nadir at 120 min, coinciding with the GH peak. No severe hypoglycemia occurred. Mean GH peak values clustered between 5 and 7 ng/mL, with most children exceeding 7 ng/mL. Among patients with short stature (height SDS < -2.0), 73% (11/15) achieved GH > 5 ng/mL and 67% (10/15) exceeded 7 ng/mL, suggesting that this cutoff shift may have limited clinical impact in this small subgroup. Most children achieved GH peak by 120 minutes, coinciding with the glycemic nadir without severe hypoglycemia. These findings support the feasibility of a shortened GST protocol and suggest that mechanisms beyond hypoglycemia may contribute to glucagon-induced GH release. The shift from 5 to 7 ng/mL had minimal impact on classification, particularly when auxological criteria were considered. Larger prospective studies are needed to clarify underlying mechanisms and establish more robust diagnostic parameter.