Comparison of glucagon stimulation test and low dose ACTH test in assessing hypothalamic-pituitary-adrenal (HPA) axis in children

Introduction: Children with a pituitary hormone deficiency are at risk for secondary adrenal insufficiency (AI). A stimulation test is usually performed for diagnosing AI, evaluating both the hypothalamic-pituitary-adrenal and growth hormone (GH)-IGF-1 axes. This single test is preferred by clinicians and is considerably more tolerable by patients. The objective of this study was to evaluate the glucagon stimulation test (GST), which is commonly used to assess both axes. Its diagnostic capability for GH deficiency is high and well accepted, however its utility for determining secondary AI has not been well established. Methods: This retrospective study involved 120 patients under 18 years of age with short stature who had undergone both a GST and low dose ACTH stimulation test (LDACTH test). Twenty-six children who had more than 6 months elapsed between the two tests were excluded from the study. The study was conducted on patients of the Pediatric Endocrinology Department at Soroka University Hospital, a tertiary medical centre in Beer Sheva, Israel. Statistical analyses were carried out via IBM SPSS (v. 22), with a significance level determined at p <.05. Results: Different cortisol cut-off values were assessed for GST and it was determined that the highest combined sensitivity and specificity yielded a cut-off point of 320 nmol/L (56% sensitivity and 83% specificity) while the currently accepted cut-off value (500 nmol/L) yielded 100% sensitivity and 6% specificity. Conclusion: The results of this study show that GST is not an optimal tool for diagnosing secondary AI. Therefore, clinicians using this test should interpret its results with caution.