Dehydroepiandrosterone Sulfate (DHEAS) as a Biomarker for Diagnosing Adrenal Insufficiency: A Comprehensive Review

Abstract

Background: Adrenal insufficiency represents a serious hormonal disorder that can become life-threatening, yet its vague symptoms often make it difficult to diagnose promptly. Current diagnostic methods face significant limitations due to biological variation, daily hormonal rhythms, and practical barriers.

Methods: We conducted a prospective study of 100 consecutive patients presenting with symptoms suggestive of adrenal insufficiency. Morning fasting blood samples were collected for baseline cortisol, ACTH, and DHEAS measurements. Adrenal insufficiency was confirmed using standard-dose ACTH stimulation testing. Diagnostic performance was evaluated by calculating sensitivity, specificity, and AUROC for each biomarker at established cutoff values.

Results: Of 100 patients evaluated, 15 (15%) were diagnosed with adrenal insufficiency—10 with secondary and 5 with primary hypoadrenalism. Baseline cortisol demonstrated 96% sensitivity but only 30-40% specificity at a cutoff of <10 μg/dL (AUROC 0.81). DHEAS showed 90–92% sensitivity with a superior specificity of 43-46% at <100 μg/dL (AUROC 0.81). Risk stratification revealed that patients with cortisol ≥10 μg/dL or cortisol 5-9.9 μg/dL plus DHEAS ≥60 μg/dL had very low diagnosis rates (1.2–1.3%), while combined cortisol <5 μg/dL and DHEAS <25 μg/dL identified high-risk patients with a 72.2% diagnosis rate.

Conclusions: DHEAS demonstrates superior specificity compared to cortisol while maintaining comparable sensitivity and discriminatory power. Combined biomarker assessment enables efficient risk stratification, identifying patients requiring dynamic testing while avoiding unnecessary procedures in low-risk individuals. Integrating DHEAS into diagnostic algorithms enhances early detection and optimizes resource utilization in evaluating suspected adrenal insufficiency.