The Diagnostic Accuracy of Dehydroepiandrosterone Sulfate in Diagnosing Adrenal Insufficiency

Background: Evaluation for adrenal insufficiency (AI) includes dynamic testing that is cumbersome, expensive, and may not always be accessible. Our objective was to evaluate the diagnostic accuracy of dehydroepiandrosterone sulfate (DHEAS) in diagnosing AI. Methods: This is a single-center retrospective study of patients evaluated for AI between July 10th, 2012 to January 7th, 2020 who underwent Cosyntropin stimulation testing (CST) or Insulin tolerance test (ITT), and had baseline measurement of DHEAS. Diagnosis of adrenal insufficiency was based on peak cortisol of <18 ug/dL during either CST or ITT. Results: We identified 491 patients (379 [77.2%] women, median age 42 years [range 18–84]) who met inclusion criteria. Primary adrenal insufficiency (PAI) was diagnosed in 16 (3%) patients, secondary adrenal insufficiency (SAI) was diagnosed in 211 (43%) patients, and AI was excluded in 264 (54%) patients. CST was performed in 478 (97%) patients, ITT was done in 45 (9%) patients, with 32 patients having both CST and ITT performed. Using a peak cortisol of <18 mcg/dl during CST to diagnose AI, ROC analysis of DHEAS demonstrated an area under the curve of 0.79, p<0.0001. A DHEAS cutoff of 100 mcg/dL excluded AI with a sensitivity of 93%, specificity of 41%, and a false negative rate of 3%. A DHEAS cut-off of 25 mcg/dl diagnosed AI with a false positive rate of 9% (Sensitivity 57% and specificity 85%). Notably, of 32 patients who had both CST and ITT performed, the diagnosis of AI was concordant in only 5 patients, while additional 27 patients had discordant results (26 were diagnosed with SAI based on ITT, but with a normal CST, and 1 patient was diagnosed with AI on CST but not on ITT). When excluding the 27 patients with discordant results, the overall performance of DHEAS in diagnosis of AI based on CST has not changed. Conclusion: DHEAS is a valuable baseline diagnostic test for AI. DHEAS >100 mcg/dl predicts a normal response during CST with a false negative rate of 3%, while DHEAS <25 mcg/dl is reflective of underlying adrenal insufficiency and predicts an abnormal CST with a false positive rate of 9%. In these situations, CST can be avoided.