SAT-441 - Basal Dehydroepiandrosterone Sulfate as A Biomarker of Adrenal Insufficiency: A Systematic Review of Diagnostic Utility

Objective: A few studies have investigated the dehydroepiandrosterone sulfate (DHEA-S) measurement as a marker of adrenal insufficiency (AI). However, evidence supporting its use as a diagnostic tool is limited. This systematic review assesses how does DHEA-S correlates with cosyntropin stimulation test (CST) or insulin tolerance test (ITT) and proposes guidance for its use.

Methods: Using the PICOT framework, a systematic search was done in PubMed and Embase (up to Jan 1st, 2026). Studies that had participants with adrenal insufficiency risk that underwent Hypothalamic-Pituitary-Adrenal (HPA) evaluation with CST or ITT as well as DHEA-S measurements were included. AI was defined based on basal cortisol, standard and low dose CST, or ITT. Patients should have no prior known AI or hormonal replacement. QUADAS-2 was used for risk of bias.

Results: From initial 267 studies, six met inclusion criteria (1806 participants; mean age 50yo; 65% female). Methodological divergences did not allow statistical comparisons between studies. Overall, serum DHEA-S levels were consistently lower in patients with AI. Four studies compared DHEA-S performance to CST and overall. They are summarized as follows: 1) log-transformed DHEA-S value of -0.853 had an AUC 0.838, 70.3% sensitivity, 100% specificity diagnosing AI compared to CST; 2) DHEA-S < 100mcg/dL had 92% sensitivity and 46% specificity diagnosing AI compared to CST. Additionally, when 8AM cortisol between 5-9.9 a basal DHEAS ≥60 mcg/dL was able to rule out AI in nearly 99% of cases; 3) the cortisol/DHEA-S molar ratio response to CST was not equimolar when HPA axis was abnormal. Two studies compared DHEA-S performance to ITT: 1) DHEA-S had AUC 0.98, a near 100% sensitivity for values >53.5mcg/dL, and 100% specificity for values < 14mcg/dL, while CST compared to ITT had AUC 0.894 (no sensitivity or specificity disclosed); 2) in adults up to 30yo, DHEA-S z-score of 2 had 100% sensitivity and specificity predicting AI compared to ITT. In adults >50yo, AUC = 0.77 and the z-score of 1.42 predicted AI only in 70% of cases.

Conclusion: This analysis gathered data from studies that evaluated individuals who underwent AI investigation and DHEA-S measurement. More data is needed to further explore these initial findings. However, when compared to CST, two studies showed specificity ranging from 70-92%. When 8 AM cortisol is 5 – 10 ug/dL baseline DHEA-S >60mcg/dl only 1.3% of individuals have AI, making it meaningful to rule out AI without the need of further stimulation test. When compared to ITT, results are more consistent with sensitivity and specificity reaching nearly 100%, especially in younger patients. Collectively, these are promising initial findings that showed potential utility for DHEA-S as a marker of adrenal insufficiency, potentially avoiding dynamic testing. However, further studies need to be done to replicate these findings.

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