Context: Population-based studies of associations between subclinical hypercortisolism and risk for disease states, such as type 2 diabetes mellitus, have been difficult to assess because of imprecise measures of glucocorticoid exposure. Alternative measures (salivary cortisol and adrenal gland volume) have not been systematically compared to 24-hour urine free cortisol (UFC) in a healthy population.

Objective: Our objectives were (1) to determine if 24-hour UFC and total daily salivary cortisol correlated with (a) each other, (b) adrenal gland volume, and (c) salivary cortisol following dexamethasone suppression and (2) to evaluate the association of adrenal gland volume with salivary cortisol following dexamethasone suppression.

Design, Setting, and Participants: This was a cross-sectional study of 20 healthy, pre-menopausal African-American women ages 18-45 years.

Main Outcome Measures: Salivary cortisol was assessed at six time points throughout the day simultaneous with 24-hour UFC collection. Adrenal gland volume was measured by CT scan. Dexamethasone-suppressed salivary cortisol was measured at 0800 following administration of 0.5 mg dexamethasone at 2300 the prior evening.

Results: Dexamethasone-suppressed salivary cortisol levels correlated strongly with individual, timed salivary cortisol measurements, total daily salivary cortisol (r_s=0.75; p=0.0001; n=20), and adrenal gland volume (r_s=0.66; p=0.004; n=17). Total daily salivary cortisol and adrenal gland volume also correlated (r_s=0.46; p-value=0.04; n=19). In contrast, 24-hour UFC levels did not correlate with any of the other hypothalamic-pituitary-adrenal axis measures.

Conclusion: Dexamethasone suppression test or adrenal gland volume may be alternative measures for characterizing subtle subclinical hypercortisolism in healthy adults.