Diagnosing adrenal insufficiency (AI) often requires complex testing which can be time consuming and expensive. Dehydroepiandrosterone sulfate (DHEAS) is a promising marker of hypothalamic-pituitary-adrenal (HPA) axis function, however its diagnostic performance has not yet been evaluated in a large-scale study.

Evaluate the performance of DHEAS and baseline cortisol in assessing AI.

Single-center retrospective cohort study.

Referral center.

Adults who underwent Cosyntropin stimulation testing (CST) between 2005-2023 and had DHEAS measured within 3 months prior to CST.

Area under receiver operating characteristic curve (AUROC) for DHEAS and baseline cortisol. Prevalence of AI based on various DHEAS and baseline cortisol concentrations.

Among 1135 patients, 195 (17.2%) had AI. Both baseline cortisol and DHEAS independently had good diagnostic performance with AUROC 0.81 (95% CI 0.77-0.84) and 0.81 (95% CI 0.78-0.85), respectively. Time of CST performance had no significant effect on diagnostic accuracy of baseline cortisol while recent glucocorticoid use decreased diagnostic performance of DHEAS (AUROC 0.72 vs 0.83). Only 1.2% of patients with baseline cortisol ≥10 mcg/dL had AI based on CST. Among patients with baseline cortisol between 5-9.9 mcg/dL, only 1.3% had AI if DHEAS was ≥60 mcg/dL. Conversely, the majority (72.2%) of patients with both baseline cortisol <5 mcg/dL and DHEAS <25 mcg/dL were found to have AI.

DHEAS has good diagnostic performance in assessing AI. Measuring both baseline cortisol and DHEAS concentrations may eliminate the need for further dynamic testing in many patients.