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Purpose: Glucagon stimulation test (GST) is used to assess the hypothalamo-pituitary-adrenal (HPA) and growth hormone (GH) axes with an incompletely defined mechanism. We aimed to assess if glucagon acted through fibroblast growth factor-21 (FGF-21) to stimulate cortisol and GH secretion. The secondary outcome was to determine the relationship of FGF-21 with variable GH responses to GST in obesity., Methods: A total of 26 healthy participants; 11 obese (body mass index (BMI) > 30 kg/m 2 ) and 15 leans (BMI < 25 kg/m 2 ) were included. Basal pituitary and target hormone levels were measured and GST was performed. During GST, glucose, insulin, cortisol, GH, and FGF-21 responses were measured., Results: The mean age of the participants was 26.3±3.6 years. Glucagon resulted in significant increases in FGF-21, glucose, insulin, cortisol, and GH levels. The levels of basal cortisol, GH, FGF-21, and IGF-1 were similar in the two groups. The peak GH and area under the curve (AUC) (GH) responses to GST in the obese group were lower than those of the normal-weight group with a different pattern of response. There were no differences between the groups in terms of peak cortisol, AUC (cortisol) , peak insulin, AUC (insulin) , peak FGF-21, and AUC (FGF21) . Obesity was associated with significantly increased glucose and insulin responses and slightly decreased FGF-21 response to glucagon., Conclusion: Obesity was associated with blunted and delayed GH, but preserved cortisol responses to GST. This is the first study showing that glucagon stimulates the HPA and GH axis independently from FGF-21. The delayed GH response to GST in obesity does not seem to be related to FGF-21., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., 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.

Context: Diagnosis of secondary adrenal insufficiency and GH deficiency requires evaluation by dynamic stimulation tests in most cases. Although insulin tolerance test (ITT) is accepted as the gold-standard test for the evaluation of both hypothalamo-pituitary-adrenal (HPA) and (GH)-IGF-1 axes, the test is cumbersome. In clinical practice, low-dose adrenocorticotrophic hormone (ACTH) stimulation test is a sensitive, safe and easily applicable alternative to ITT. Although it takes more time, glucagon stimulation test (GST) is also a good alternative to ITT and can evaluate both axes., Objective: The primary aim of this study was to compare the ITT, low-dose ACTH and GSTs in the evaluation of HPA and GH-IGF-1 axes in patients with pituitary disorders and to evaluate the repeatability of all three tests., Design: ITT, low-dose ACTH and GSTs were performed in all 129 patients, and the tests were repeated in 66 of these patients., Setting: Erciyes University Medical School, Department of Endocrinology., Patients or Other Participants: One hundred and twenty-nine adult patients (76 women, 53 men) with pituitary disorder were included in the study., Main Outcome Measure(s): The cortisol and GH responses of patients to dynamic tests., Results: Peak cortisol levels obtained during ITT were significantly lower than the values obtained during both low-dose ACTH and GSTs. Peak cortisol levels obtained during the GST were lower than those found during the low dose ACTH stimulation test. Peak GH responses were found to be higher in GST than in ITT. All three tests had good reproducibility., Conclusions: Any of 3 tests can be used in the evaluation of the HPA axis and either GST or the ITT can be used in the evaluation of the GH-IGF-1 axis but cut-off levels for the insufficiency of HPA or GH-IGF-1 axis should be individualized for each test., (© 2014 John Wiley & Sons Ltd.)

Objective: The investigations regarding the effect of obstructive sleep apnoea syndrome (OSAS) on hypothalamo-pituitary-adrenal (HPA) axis revealed conflicting results. We aimed to evaluate the effects of OSAS on HPA-axis with dynamic tests., Methods: This study was carried out on 26 patients with OSAS and 15 subjects without OSAS which, were defined according to the International Classification of Sleep Disorders. Patients were enrolled from either Endocrinology outpatient clinic or Neurology Sleep Center. Participants for the control group were included from the patients admitting to Endocrinology Department with the complaint of obesity or volunteers from hospital staff. All the participants were evaluated by polysomnography (PSG) and dynamic tests of HPA axis (dexamethasone suppression test, 1 and 250μg ACTH and glucagon stimulation tests)., Results: Serum basal and peak cortisol levels were found to be lower in OSAS patients when compared to the control group during 1μg ACTH and glucagon stimulation tests. When the area under curve (AUC) of cortisol responses to dynamic stimulation tests were calculated according to trapezoid formula, patients with OSAS were found to have lower values compared to control group. AUC responses of all three dynamic stimulation tests were found to be negatively correlated with AHI., Conclusion: OSAS is associated with relative hypocortisolemia in the morning with reduced responses to 1 and 250μg ACTH and glucagon stimulation tests., (Copyright © 2012. Published by Elsevier B.V.)

Evaluation of the HPA axis is still a challenge; due to different sensitivities and stimulation efficiencies of dynamic tests, lack of standard assays for cortisol measurement and lack of data regarding the effects of age and gender on the results of the HPA axis evaluation with different dynamic tests. This study was performed to compare 1 μg ACTH, 250 μg ACTH and glucagon tests in the evaluation of HPA axis. The study was carried out on 55 healthy individuals (28 men, 27 women). 10-12 volunteers were included from every decades between 20 and 70 years. Low dose short synacthen test (1 μg ACTH), standard dose short synacthen test (250 μg ACTH) and glucagon tests were performed consecutively. The mean peak cortisol response to standard dose ACTH stimulation test was found to be significantly higher than the low dose ACTH and glucagon stimulation tests. The mean peak cortisol responses to low dose ACTH and the glucagon stimulation tests were not significantly different. The mean peak cortisol responses did not differ significantly between different age or sex groups. The lowest peak cortisol responses obtained after low dose ACTH and glucagon stimulation tests were 12.5 and 9.1 μg/dl respectively in the volunteers who all had cortisol responses higher than 20 μg/dl after standard dose ACTH stimulation test. The lowest cortisol responses obtained during 250 μg ACTH, 1 μg ACTH and glucagon stimulation tests were found to be 20.1, 12.5 and 9.1 μg/dl in a known group of healthy people. So the consideration of appropriate hormonal cut-off levels for each test seems reasonable. The age, sex and body mass indeces were not shown to affect the cortisol response to dynamic stimulation tests., (© Springer Science+Business Media, LLC 2010)