RESUMEN
BACKGROUND: Traditional testing of the hypothalamic-pituitary-adrenal axis function has essentially relied upon the insulin tolerance test or the metyrapone test(both tests are not only uncomfortable, but are also dangerous). The standard ACTH stimulation test uses an extremely supra-physiologic amount(250f microgram) of ACTH to evaluate a physiological response, which may result in a false normal response. The 1microgram rapid ACTH stimulation test is more physiological and more sensitive than the standard test, but there exist much controversy about when the serum cortisol should be measured or what the most appropriate cut-off point is for normality or whether the 1microgram ACTH commercial solution is needed. The aims of this study were to investigate 1) whether 1microgram of ACTH is an appropriate amount to stimulate the adrenal gland of patients that have suspected central adrenal insufficiency compared with insulin tolerance test(ITT) and 2) the diagnostic value of the 1microgram rapid ACTH stimulation test according to timing of sampling of serum cortisol. METHODS: In order to evaluate the dose-response relationship between ACTH and cortisol, we performed the ITT in 77 patients with suspected central adrenal insufficiency with serial measurements of serum cortisol and plasma ACTH. We drew the blood samples in 10 min intervals between 10 and 60 min after the administration of 1microgram ACTH in 39 patients with central adrenal insufficiency and in 38 pituitary control patients with pituitary. ITT was used to confirm the diseases for the patients of central adrenal insufficiency, but for pituitary control patients, the ITT indicated normality in the patients. Also, all subjects underwent the 250microgram rapid ACTH stimulation test, and we compared the diagnostic value of the 1microgram ACTH stimulation test with the 250microgram test. RESULTS: 1) The plasma ACTH level after the 1microgram ACTH stimulation test, even if it was be assumed as approximately 300pg/mL, was expected to be sufficient enough to stimulate the adrenal cortex normally(serum cortisol levels >18microgram/dL) compared to the plasma ACTH level in the ITT. 2) The sensitivity and specificity of the 1microgram rapid ACTH stimulation test was highest with 92.3% and 84.2%, respectively, when serum cortisol levels were measured at 20, 30, and 40 min after the ACTH injection. The 1microgram rapid ACTH stimulation test was more sensitive than the 250microgram ACTH test(sensitivity: 92.3%, specificity: 71.8%). CONCLUSION: The 1microgram rapid ACTH stimulation test was more sensitive test in patients with suspected central adrenal insufficiency, and blood samples for cortisol levels should be drawn at 20, 30, and 40 min after ACTH administration.