The time of day that cosyntropin (ACTH) stimulation testing takes place does not affect the percentages of failed, borderline, or passed results in the evaluation of adrenal insufficiency (AI) (Clin Biochem 2018; Moreover, cortisol levels via a single 30-minute test increases the likelihood of patients having a false-positive diagnosis of AI. Based on these findings, the authors conclude that a single serum cortisol assessment at 60 minutes after ACTH administration yields the best diagnostic accuracy. They called for prospective studies of larger populations to confirm their findings.

ACTH stimulation testing is considered the gold standard for investigating primary AI and may be an effective alternative to insulin tolerance testing in the workup of secondary AI. However, reported testing proce-dures vary, with some sites using only 30-minute results and others performing both 30- and 60-minute testing. Testing sites also have different practices about the time of day (morning versus afternoon) that ACTH testing takes place. To assess whether both 30- and 60-minute results are necessary and whether the timing of testing affects outcomes, the researchers conducted a retrospective study of all ACTH testing performed during a 10-year period at the Halifax (Canada) Neuropituitary Program.

In all, there were 431 ACTH stimulation tests; the researchers excluded 92 due to medications the patients were taking or because the patients had already been diagnosed with primary AI. The cutoff for ACTH testing was 18 mcg/dL (500 nmol/L) with a test “fail” if both 30- and 60-minute results were below this level, a “borderline pass” if either a 30- or 60-minute value was below the cutoff, and a pass if results at both time frames were above the cutoff. The investigators considered the time of day in three blocks of time: early morning (between 8 a.m. and 10 a.m.); late morning (between 10:01 a.m. and 12 p.m.); and afternoon (after 12 p.m.).

When considering ACTH results by time of day, the investigators found no difference in mean cortisol levels at 30 or 60 minutes. However, when comparing testing at two time points (30 and 60 minutes) versus one (60 minutes), they discovered that 13.4% of patients failed to reach the cutoff at 30 minutes but went on to reach it at the 60-minute mark. Conversely, just 0.6% who met the cutoff at 30 minutes failed to reach it at 60 minutes.