On the meaning of low-dose ACTH(1-24) tests to assess functionality of thehypothalamic-pituitary-adrenal axis

To analyse further the ACTH(1-24) low-dose test, which is of clinical inter est, we have examined the dose-response relationship between plasma ACTH(1- 24) and cortisol concentrations after i.v. administration of increasing dos es (1, 5 or 250 mu g) of ACTH(1-24) as a bolus, In addition, we have measur ed plasma ACTH(1-39) and cortisol levels after an insulin tolerance test (I TT), Although there was a dose-response relationship between plasma ACTH(1- 24) immunoreactivity and the dose injected, cortisol peaks were comparable, but lower than those reached after an ITT, Under these experimental condit ions, an increase in plasma ACTH as low as 13 pmol/l (i.e. the increase obt ained with the 1 mu g dose) induced a near maximal cortisol response. Follo wing injection of 1 mu g ACTH(124), peak ACTH values were short lasting, si milar to physiological daily bursts. After injection of 5 mu g ACTH(1-24), plasma ACTH concentrations were higher than those reached during an ITT, bu t clearly shorter lasting. Injection of 250 mu g ACTH(1-24) induced strikin gly supraphysiological levels of plasma ACTH, Mie conclude that neither reg ular nor low-dose ACTH tests can fully reproduce the ITT. Our observations strongly suggest that the low-dose ACTH(1-24) test (1 mu g) can be useful t o estimate the adrenal sensitivity under basal, physiological conditions.