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Dehydroepiandrosterone Sulfate in the Assessment of the Hypothalamic-Pituitary-Adrenal Axis

Division of Endocrinology, Diabetes, and Clinical Nutrition (S.F., S.J., S.A., P.D., E.R.C., C.S.), Inselspital, and Institute of Social and Preventive Medicine (S.A., M.Z., C.S.), Division of Clinical Epidemiology and Biostatistics, University of Bern, CH-3010 Bern, Switzerland

Address all correspondence and requests for reprints to: Christoph Stettler, M.D., Division of Endocrinology, Diabetes, and Clinical Nutrition, Inselspital, University of Bern, CH-3010 Bern, Switzerland. E-mail: christoph.stettler{at}insel.ch.

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-S. 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.

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