A comparison of cortisol responses to the insulin tolerance test and glucagon stimulation test in patients with suspected adrenal insufficiency

Aim Evaluation of the hypothalamic-pituitary-adrenal (HPA) axis is highly important as a key determinant of the glucocorticoid replacement decision in patients with suspected adrenal insufficiency. This study compared the cortisol responses to the insulin tolerance test (ITT) and glucagon stimulation test (GST) in patients with suspected adrenal insufficiency. Methods One hundred seventeen patients (median age: 41.59, min-max 17.0-73.0 years, 75% female) with suspected adrenal insufficiency were included in this cross-sectional study. The ITT and GST were applied to all patients in a random order following overnight fasting. Results The mean peak cortisol level was 11.71 in the ITT and 17.45 in the GST, the difference being statistically significant (<em>t</em> = -11.016, <em>P</em> < .001). Examination of the cross distributions of ITT and GST response status revealed a negative GST response in 55.6% and a positive response in 44.4% of the patients with no ITT response. The mean Δcortisol values were 4.77 in the ITT and 10.88 in the GST, the increase in the cortisol response being significantly higher compared to the ITT (<em>P</em> < .001). In terms of time-dependent changes in cortisol levels, a later-onset and more prolonged cortisol response was observed in the GST. Conclusions The study findings revealed that both peak cortisol levels and Δcortisol values detected in the GST were significantly higher than those in the ITT when the two tests were applied to the same patients. The GST emerged as a reliable and sufficient alternative dynamic test compared to the ITT, regarded as the gold standard in the evaluation of adrenal insufficiency.