The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults Zuleyha Karaca • Ayhan Lale • Fatih Tanriverdi • Mustafa Kula • Kursad Unluhizarci • Fahrettin Kelestimur Published online: 9 November 2010 Ó Springer Science+Business Media, LLC 2010 Abstract 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 mea- surement 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 lg ACTH, 250 lg 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 vol- unteers were included from every decades between 20 and 70 years. Low dose short synacthen test (1 lg ACTH), standard dose short synacthen test (250 lg 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 lg/dl respectively in the volunteers who all had cortisol responses higher than 20 lg/dl after standard dose ACTH stimulation test. The lowest cortisol responses obtained during 250 lg ACTH, 1 lg ACTH and glucagon stimulation tests were found to be 20.1, 12.5 and 9.1 lg/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. Keywords Glucagon stimulation test Á ACTH stimulation test Á HPA axis Á Healthy adults Introduction There are different tests used in the evaluation of the hypothalamo-pituitary-adrenal (HPA) axis. Insulin toler- ance test (ITT) has been suggested as the gold standard test for examining HPA axis function [1–3]. The disadvantages of the ITT are to be unpleasant for the patients and the need of close medical supervision during test. It is contraindi- cated in patients with ischemic heart disease, arrhythmia or epilepsy and should be used with caution in the older patients. HPA axis may also be evaluated by other tests such as ACTH (1 and 250 lg ACTH 1–24), metyrapone, glucagon and CRH stimulation tests. The cortisol response to 250 lg (standard dose) ACTH stimulation at 30 min is demon- strated to be correlated with ITT [4, 5]. But the standard dose ACTH stimulation was thought to be non-physio- logical by some authors and 1 lg (low dose) ACTH stimulation has emerged in order to prevent the supra- physiological stimulation of the adrenal glands [6, 7]. Although the low dose ACTH stimulation test was reported to be more correlated with ITT than the standard dose ACTH in patients following pituitary surgery [8], the low and standard dose ACTH stimulation tests were found to be Z. Karaca Á A. Lale Á F. Tanriverdi Á K. Unluhizarci Á F. Kelestimur (&) Department of Endocrinology, Erciyes University Medical School, 38039 Kayseri, Turkey e-mail: fktimur@erciyes.edu.tr M. Kula Department of Nucleer Medicine, Erciyes University Medical School, Kayseri, Turkey 123 Pituitary (2011) 14:134–140 DOI 10.1007/s11102-010-0270-3