The midnight to morning urinary cortisol increment is an accurate, noninvasive method for assessment of the hypothalamic-pituitary-adrenal axis

The optimal method for assessing the hypothalamic-pituitary-adrenal axis (H PA) remains controversial. The insulin tolerance test (ITT) is considered t he gold standard, but is invasive and potentially dangerous. The short Syna cthen test (SST) is the most commonly used alternative, but its concordance with the ITT is pear. Using sleep as a reliable stimulus to ACTH release, we proposed that the increment in urinary cortisol levels between midnight and waking could provide a noninvasive, physiological means for the assessm ent of the HPA axis. Double voided urine samples were collected at home at midnight and waking in 40 patients with pituitary disease and 40 controls. Cortisol and creatinine levels were measured, and the cortisol/creatinine ( Cort/Cr) ratio was calculated. The Cort/Cr increment was defined as the mor ning Cort/Cr ratio minus the midnight Cort/Cr ratio. The Cort/Cr increment of the patients was compared to the results of their ITT or SST. Using the results from the 40 controls, a normal Cort/Cr increment was defined as gre ater then 9. The positive predictive value of a Cort/Cr increment for the d iagnosis of HPA insufficiency was 95%. These findings suggest that the midn ight to morning Cort/Cr increment is a reliable, noninvasive alternative to the ITT/SST for assessment of the HPA.