The low dose (1 microg) ACTH stimulation test for assessment of the hypothalamo-pituitary-adrenal axis

Traditional testing of the hypothalamo-pituitary-adrenal axis function has relied essentially upon the insulin tolerance test or the metyrapone challenge: both tests are not only uncomfortable, but carry also real dangers. The standard ACTH stimulation test uses an extremely hyperphysiological amount (250 microg) of ACTH to evaluate a physiologic response, which may result in false normal responses. The proposed low dose (1 microg) ACTH test is more physiological and more sensitive, especially in cases of mild adrenal insufficiency and allows also to assess pituitary-adrenal suppression after long-term treatment with glucocorticoids. According to the rules of evidence-based medicine, the low dose ACTH test should replace the conventional 250 microg test when evaluating for central adrenal insufficiency.