A low dose ACTH test to assess the function of the hypothalamic–pituitary–adrenal axis

OBJECTIVE  The insulin tolerance test (ITT) has long been used to assess the hypothalamic–pituitary–adrenal axis, but may be hazardous. The standard synthetic ACTH (Synacthen) test has been advocated as a substitute but is sometimes insensitive. In this study the ITT has been compared to a low dose ACTH stimulation test (1 μg) and the standard ACTH stimulation test (250 μg).
SUBJECTS  Twenty-seven subjects were studied, 24 with verified or suspected hypothalamic–pituitary disorders and three on long-term glucocorticoid therapy.
DESIGN  Insulin tolerance, low dose ACTH and standard ACTH tests were performed in all patients. The ITT was performed less than 48 hours after the ACTH tests. Synacthen was administered as an intravenous bolus.
MEASUREMENTS  Serum cortisol values were determined by radioimmunoassay. The peak cortisol value during ITT was compared to the cortisol levels during the ACTH tests.
RESULTS  There was a highly significant correlation between peak cortisol values during ITT and cortisol levels after 20–60 minutes in the low dose ACTH test ( r _s = 0.91–0.93; P < 0.0001) and after 30 and 60 minutes in the standard ACTH test ( r _s= 0.85 and 0.89 respectively; P < 0.0001). Four patients showed discrepancies between the three tests.
CONCLUSIONS  The 1-μg ACTH test follows the ITT more closely and may be more sensitive than the standard ACTH test in detecting more subtle insufficiency of the hypothalamic–pituitary–adrenal axis. The standard ACTH test and the insulin tolerance test may thus be replaced by the 1-μg ACTH test in screening for secondary cortisol insufficiency. We recommend that serum cortisol is measured before and 30 and 40 minutes after the ACTH injection.