Comparison of a combination test (1 µg ACTH test plus glucagon test) versus 1 µg ACTH test and glucagon test in the evaluation of the hypothalamic-pituitary-adrenal axis in patients with pituitary disorders

ABSTRACT Objective To investigate whether a combination of the low-dose (1 µg) adrenocorticotropin (ACTH) stimulation test and glucagon stimulation test (GST) could overcome the problem of equivocal results with the GST or ACTH test alone in patients with pituitary disorders. Subjects and methods The study included 41 adult patients with pituitary disorders and 20 healthy subjects who underwent evaluation of cortisol response to ACTH, GST, and a combination of both tests. Blood samples for cortisol measurement were obtained at baseline and 30, 60, 90, and 120 minutes after intravenous administration of ACTH 1 μg and 90, 120, 150, 180, 210, and 240 minutes after subcutaneous injection of glucagon 1 mg. The combination test was performed by injecting ACTH 1 µg at the 180-minute time point of the GST, with blood samples for cortisol measurement obtained at 210 and 240 minutes. Results Overall, 28 patients with normal cortisol response to both tests also had a normal cortisol response to the combination test. Ten patients with adrenal insufficiency in both tests also had adrenal insufficiency in the combination test, including a patient who had a peak cortisol value of 12.4 µg/dL (which is the cutoff value for the combination test). Two patients with adrenal insufficiency in the ACTH stimulation test and one patient with adrenal insufficiency in the GST had normal cortisol responses to the combination test. Conclusion By using an appropriate cutoff value, the combination test may offer additional information in patients with equivocal results in the GST and ACTH stimulation test.

Is biochemical hypoglycemia necessary during an insulin tolerance test?

ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8