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: 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 centre.

Design and Patients: In 70 consecutive patients insulin tolerance test (ITT) was accompanied by measurement of basal DHEA-S. Assessment of HPA axis was based on peak cortisol response in ITT (normal 550 nmol/l). 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 versus -0.62, p<0.0001). In individuals up to 30 years a z-score of -2.0 had 100% sensitivity and specificity regarding HPA function (area under ROC curve 1.00) while z-scores provided 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 in patients with pituitary macroadenoma but further studies are needed to consolidate these findings.