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

Abstract

Objective 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. Methods 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. Results 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. Conclusions 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.

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis

“…This was a single‐centre study and timing of cortisol stimulation test was intentionally flexible to minimally disrupt routine inpatient hospital care. There is suggestion in the endocrinology literature that afternoon SD‐SST administration may stimulate a more robust cortisol response compared to morning testing in the general population; however, a subgroup analysis revealed no significant difference in prevalence of RAI when comparing morning vs afternoon administration 34 . We did not measure adrenocorticotropic hormone or aldosterone, which are two other key hormones within the HPA axis.…”

“…There is suggestion in the endocrinology literature that afternoon SD-SST administration may stimulate a more robust cortisol response compared to morning testing in the general population; however, a subgroup analysis revealed no significant difference in prevalence of RAI when comparing morning vs afternoon administration. 34 We did not measure adrenocorticotropic hormone or aldosterone, which are two other key hormones within the HPA axis. Additional studies with concurrent measurements of these hormones will be helpful to better assess the degree to which other levels of the HPA axis are altered.…”

New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol Assays

“…Serum cortisol concentrations are approximately 20% lower with the newer assays compared with the older assays in some studies [ 8 , 13 , 15 , 26 , 27 ]. However, other studies have actually suggested that LC-MS/MS yielded a higher peak cortisol cutoff after ACTH stimulation than cortisol measured by immunoassay [ 28 , 29 ]. Considering these discrepancies in the literature, ACTH-stimulated cortisol threshold values using new, more-specific cortisol assays are needed to accurately diagnose AI and minimize overtreatment.…”

A Phase 1 Study to Investigate the Effects of Cortexolone 17α‐Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity

“…It exerts local antiandrogenic activity by binding human androgen receptors to displace endogenous androgenic hormones 1 and is rapidly metabolized in plasma into cortexolone (also known as 11-deoxycortisol)-a naturally occurring corticosteroid. 2 The use of available topical and oral antiandrogenic therapies for AGA and acne is currently limited because of undesirable systemic side effects, such as reduced libido, impairment of spermatogenesis, and feminization of male fetuses in pregnant women. 3,4 Cortexolone 17α-propionate has been designed as a topical androgen receptor inhibitor with comparable efficacy to minoxidil for the treatment of AGA 5 and tretinoin for the treatment of acne, 6,7 but without the significant systemic activity seen with currently available oral antiandrogenic therapies.…”