Serum dehydroepiandrosterone sulfate in assessing the integrity of the hypothalamic-pituitary-adrenal axis

OBJECTIVE: To evaluate the relationship between age- and gender-adjusted dehydroepiandrosterone sulfate (DHEA-S) levels and low-dose adrenocorticotropic hormone (ACTH) stimulation in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, in patients who were at risk of HPA insufficiency, including those currently being treated with glucocorticoids. METHODS: Forty-six participants with a suspicion of secondary adrenal insufficiency were recruited from the Diabetes and Endocrinology Clinic at Ramathibodi Hospital, Mahidol University, Bangkok. Low-dose (1 μg) ACTH stimulation was performed in every participants, and serum DHEA-S was measured at baseline before ACTH injection. RESULTS: Individuals with normal age- and gender-specific DHEA-S levels had baseline serum cortisol and peak cortisol levels higher than those with reduced DHEA-S. Normal age- and gender-specific DHEA-S levels predicted intact HPA function with a sensitivity of 87.1%, a specificity of 86.7%, a positive predictive value of 93.1%, and a negative predictive value of 76.5%. To account for the age and gender dependency of DHEA-S, the DHEA-S ratio was calculated by measured DHEA-S divided by the lower limit of the respective reference range for all participants. A DHEA-S ratio of more than 1.78 had 100% sensitivity regarding intact HPA function. Area under the receiver operating characteristic [ROC] curve was 0.920. (95% CI, 0.844–0.997). CONCLUSION: Normal age- and gender-specific DHEA-S level or a DHEA-S ratio of more than 1.78 are valuable markers of HPA integrity. Serum DHEA-S may be a candidate for a less costly approach where ACTH stimulation is unavailable.