DHEAS for the prediction of subclinical Cushing's syndrome: perplexing or advantageous?

The diagnostic accuracy of dehydroepiandrosterone sulfate (DHEAS) to predict subclinical Cushing's syndrome (sCS) has been a matter of debate. The primary objective of this study was to assess the diagnostic power of DHEAS in predicting sCS. This retrospective study was conducted in a tertiary referral center and based on subjects referred between 2004 and 2014. Data of 249 subjects with adrenal incidentalomas were evaluated. We also reviewed 604 DHEAS measurements from adults, which were performed during the same period in our laboratory (LB group). Adrenocortical function, tumor size, and clinical characteristics were assessed. We diagnosed sCS in 15.2 % of the participants in the presence of ≥2 of the following; 1 mg dexamethasone suppression test >3.0 μg/dl, urinary free cortisol >70 μg/24 h, and corticotrophin (ACTH) <10 pg/ml. DHEAS levels were significantly reduced in patients with sCS (n = 38) compared to sCS (-) (n = 141) and LB groups (n = 604) (27.95, 65.90, and 66.80 µg/dl, respectively, p < 0.001) while age was comparable. The ROC curve analysis showed that the cut-off of the DHEAS with the best diagnostic accuracy for detecting sCS was 40.0 μg/dl (SN, 68 %; SP, 75; PPV, 43 %; NPV, 90 %, AUC: 0.788, p < 0.001). Logistic regression assessed the impact of age, BMI, low DHEAS (<40 μg/dl), bilateral tumors, and tumor size on the likelihood of having sCS. The strongest predictor was low DHEAS, recording an OR of 9.41. DHEAS levels are inversely associated with the extent of cortisol excess. In subjects with intermediate laboratory findings, detection of low DHEAS could be advantageous for distinguishing sCS.