Performance of DHEAS as a Screening Test for Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Prospective Study

Abstract

Context: Autonomous cortisol secretion (ACS) affects up to 30% of patients with adrenal incidentalomas (AIs). The current guidelines for ACS diagnosis are not decisive. A lower dehydroepiandrosterone sulfate (DHEAS) level is a potential biomarker, but the evidence is conflicting. Objective: This prospective study aimed to evaluate and validate the ACS screening and diagnostic accuracy of DHEAS. Methods and patients: Recruited patients with AI were screened for adrenal medullary and cortisol hypersecretion. The diagnosis of ACS was based on a serum cortisol level≥50 nmol/L following a 1-mg dexamethasone suppression test (DST) and a low-dose DST. Age- and sex-specific DHEAS ratios were also calculated. Results: In the development cohort (45 ACS and 242 non-ACS patients), the areas under the receiver operator characteristic curves (AUCs) of DHEAS and the DHEAS ratio were 0.869 (95% CI 0.824-0.906) and 0.799 (95% CI 0.748-0.844), respectively. The optimal DHEAS cutoff for diagnosing ACS was 60 μg/dL, with a sensitivity of 75.6% (95% CI 60.5-87.1) and a specificity of 81.4% (95% CI 76.4-86.5). The midnight serum cortisol level had moderate diagnostic accuracy [AUC 0.875 (95% CI 0.831-0.911)]. Suppressed adrenocorticotropic hormone (≤2.2 pmol/L) had a lower sensitivity (55.6%), and the 24-hour urinary free cortisol lacked sensitivity and specificity [AUC 0.633 (95% CI 0.603-0.721)]. In the validation cohort (14 ACS and 45 non-ACS patients), the sensitivity and specificity of the optimized DHEAS cutoff were 71.4% (95% CI 41.9-91.6) and 82.2% (95% CI 68.0-92.0), respectively. Conclusions: A single basal measurement of DHEAS is valuable for identifying ACS. Because of its stability and ease of use, the DHEAS level could be used as an ACS screening test.