Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers

Objective  No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1–24) and the cortisol profiles after standard high-dose test (250 µg) (HDT) and low-dose test (1 µg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. Design and patients  ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. Measurements  Plasma ACTH(1–24) and ACTH(1–39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1–24) and cortisol, as well as mean residence time (MRT) for ACTH(1–24) were calculated in both tests. Results  Elimination of ACTH(1–24) was faster in HDT than in LDT (MRTs of 0·14 vs 0·37, respectively, P = 0·008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52·5 min). No significant relationship was observed between AUC or Cmax of ACTH(1–24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0·77 P = 0·009; LDT: r = 0·94 P < 0·0001), but not so with Cmax (HDT: r = 0·22 P = 0·55; LDT: r = 0·57 P = 0·09). Conclusions  The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.