High-Dose ACTH Stimulation Test
This test consists of measuring serum cortisol immediately before and 30 and 60 minutes after IV injection of 250 μg of cosyntropin. This dose of cosyntropin results in pharmacologic plasma ACTH concentrations for the 60-minute duration of the test.
The advantage of the high-dose test is that the cosyntropin can be injected using the IM route, because pharmacologic plasma ACTH concentrations are still achieved.
Salivary cortisol can also be measured during this test. Salivary cortisol increases to 19 ± 0.8 ng/mL (range: 8.7–36 ng/mL) 1 hour after injection.
Eight-Hour ACTH Stimulation Test
The 8-hour test, which is now rarely performed, consists of infusing 250 μg of cosyntropin continuously over 8 hours in 500 mL of isotonic saline. A 24-hour urine specimen is collected the day before and the day of the infusion for cortisol or 17-hydroxycorticoid and creatinine determination, and serum cortisol is determined at the end of the infusion. Plasma ACTH concentrations are supraphysiologic throughout the infusion.
The 24-hour urinary excretion of 17-hydroxycorticoid should increase three-to fivefold over baseline on the day of ACTH infusion.
Two-Day ACTH Infusion Test
The 2-day ACTH infusion test is similar to the 8-hour infusion test, except that the same dose of ACTH is infused for 8 hours on 2 consecutive days.
This test may be helpful in distinguishing secondary from tertiary adrenal insufficiency. The 1-day 8-hour test is too short for this purpose, whereas longer tests add little further useful information.
Urinary excretion of 17-hydroxycorticoid should exceed 27 mg during the first 24 hours of infusion and 47 mg during the second 48 hours.
Interpretation
Low-dose stimulation test: A value of 18 μg/dL or more, before or after ACTH injection, is indicative of normal adrenal function.
High-dose stimulation test: A serum cortisol value of 20 μg/dL or more at any time during the test, including before injection, is indicative of normal adrenal function.
Eight-hour stimulation test: Serum cortisol should reach 20 μg/dL in 30–60 minutes after the infusion is begun and exceed 25 μg/mL after 6–8 hours.
