Continuous Free Cortisol Profiles in Healthy Men

CONTEXT: In humans, approximately 95% of circulating cortisol is bound to corticosteroid-binding globulin and albumin. It is only the free fraction that is biologically active and can activate signaling pathways via glucocorticoid hormone receptors in cells. Microdialysis is a well-established technique that enables the sampling of molecules in different compartments of the body, including extracellular fluid. This is the first study validating a rapid sampling microdialysis method measuring free cortisol in the subcutaneous and blood compartments of healthy volunteers. METHODS: Healthy nonsmoking volunteers (42 men, aged 18-24 years; body mass index 18-25 kg/m2) received placebo (saline), 250 μg Synacthen, or 1 mg dexamethasone with 10-minute sampling to measure total and free cortisol (subcutaneous, intravenous, and saliva) for an hour before and 4 hours after administration. RESULTS: Following stimulation by Synacthen, total serum cortisol and free cortisol in both compartments rose significantly, achieving and maintaining maximum levels between 2 and 3 hours following the stimulus. A decline in cortisol levels was evident after the administration of dexamethasone or placebo, but there was a clear pulsatile activity around lunchtime in the latter group, which was prominent in the blood compartment (total and free cortisol). There was good correlation between serum total and free cortisol (subcutaneous and intravenous) in the Synacthen and dexamethasone groups with no significant delay (less than 5 minutes) between total and free cortisol. CONCLUSIONS: This seminal study demonstrated the dynamic responses of total blood cortisol and microdialysis derived free cortisol in blood, subcutaneous tissue, and saliva in men.