Context: The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established.
Objective: The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age.
Design and setting: This was a prospective study conducted in two Pediatric Endocrinology Centers.
Patients and methods: Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon.
Results: The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P < 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified.
Conclusions: This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency.