Dehydroepiandrosterone sulfate in the assessment of the hypothalamic-pituitary-adrenal axis

Context: The role of dehydroepiandrosterone-sulfate (DHEA-S) in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with suspected insufficiency is uncertain. Objective: The objective of the study was to prospectively evaluate the diagnostic value of DHEA-S on HPA function in consecutive patients with suspected HPA insufficiency with and without pituitary lesions at a tertiary referral center. Design and Patients: In 70 consecutive patients, insulin tolerance test was accompanied by measurement of basal DHEA-5. Assessment of HPA axis was based on peak cortisol response in insulin tolerance test (normal >= 550 nmol/liter). To account for the age and gender dependency of DHEA-S, a z-score was calculated using age- and gender-specific reference values of the assay. Results: individuals with HPA insufficiency had significantly lower z-scores than those with normal HPA function (-1.66 vs. -0.62, P < 0.0001). In individuals up to 30 yr of age, a z-score of -2.0 had 100% sensitivity and specificity regarding HPA function [area under receiver operating characteristics (ROC) curve 1.00], whereas z-scores proved less useful in older individuals. In individuals with pituitary macroadenoma, a z-score below -2.0 had 100% specificity to predict HPA insufficiency (area under ROC curve 0.82). In the absence of a pituitary adenoma, the diagnostic value of the z-score was reduced (area under ROC curve 0.71). Conclusions: Individuals with HPA insufficiency have lower z-scores for DHEA-S than those with normal HPA function. There is evidence that a z-score could be of diagnostic value in assessing HPA integrity, especially in younger patients and patients with pituitary macroadenoma, but further studies are needed to consolidate these findings.