Performance of dehydroepiandrosterone sulfate and baseline cortisol in assessing adrenal insufficiency

Abstract

Context: 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.

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

Design: Single-center retrospective cohort study.

Setting: Referral center.

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

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

Results: 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.

Conclusion: 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.

Keywords: CST; DHEAS; Synacthen; cortisol; cosyntropin; diagnosis; stimulation test.