Changes in Steroid Concentrations with the Timing of Corticotropin Stimulation Testing in Participants with Adrenal Sufficiency

Abstract

To determine whether the time of day at which corticotropin stimulation testing is performed influences the steroid concentrations observed in persons with normal adrenal function. In this retrospective, secondary analysis, participants with normal adrenal function were studied to determine whether the time of corticotropin stimulation testing influenced results. Participants consisted of 2 groups: healthy volunteers who were not suspected of having adrenal insufficiency and patients being tested for adrenal insufficiency as part of their standard of care who were subsequently shown to have normal adrenal function on the basis of a peak cortisol value of at least 20 μg/dL. A high-dose corticotropin stimulation test was performed in all participants. Baseline, peak, and delta steroid concentrations were documented after corticotropin injection. Steroid concentrations were measured by tandem mass spectrometry. Multivariate analyses adjusted for patient age, sex, and baseline steroid concentrations. With progression through the day for the time of testing, the baseline cortisol concentration decreased, while the peak and delta cortisol concentration increased (P values: <.001, .007, .007, respectively). For 11-deoxycortisol, the baseline decreased, while peak and delta values increased with later testing (P values: .017, .012, .02, respectively). Peak aldosterone concentrations increased according to their baseline values (P<.001), but were unaffected by time. Peak and delta dehydroepiandrosterone concentrations increased with time (P = .015 and .021, respectively). Referring to the various criteria for adequate steroid responses to corticotropin available in the literature, the time-related differences in this small group of patients were insufficient to draw different conclusions about results of testing. Cortisol, 11-deoxycortisol, and dehydroepiandrosterone values were most influenced by testing times. In patients with borderline adrenal function who are tested at different times of the day, the modest differences we observed may be sufficient to affect conclusions about whether adrenal insufficiency is present.