Continuous Free Cortisol Profiles in Healthy Men - Validation of Microdialysis Method

Abstract 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 signalling 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 non-smoking volunteers (42 men; age 18-24 years; BMI 18-25 kg/m2) received placebo (saline), 250 µg Synacthen or 1 mg dexamethasone with ten minutely 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 (SC 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 man. </jats:sec

Continuous Free Cortisol Profiles – Circadian Rhythms in Healthy Men

The pituitary-adrenal axis had historically been considered a representative model for circadian rhythms. A recently developed portable collection device provided the opportunity to evaluate free cortisol profiles using the microdialysis approach in individuals free to conduct their day-to-day activities in their own surroundings. Methods Two separate experiments were conducted in healthy male volunteers – ten-minutely total and subcutaneous free cortisol were measured for 24-hour period in one and twenty-minutely subcutaneous free cortisol for 72 consecutive hours in free-living individuals in the other experiment. Results The characteristic circadian rhythm was evident in both serum total and subcutaneous free cortisol with the lowest levels being achieved and maintained in the hours surrounding sleep onset with peak levels occurring in every individual around waking. In all free-living individuals, the circadian rhythm was consistent across 72-hours despite a wide range of activities. All participants also showed increased cortisol following the consumption of lunch. The lowest levels during all 24 hour periods were observed during the hours following lights switch-off, at the onset of sleep Conclusions This is the first study to show up to three consecutive 24-hour measurements of subcutaneous free cortisol in healthy individuals. This, we believe is a landmark study that paves the way for ambulatory monitoring of free cortisol profiles continuously up to a period of 72 hours in a free-living individual going about their day to day activities whether in health or in diseases involving the HPA axis

Cortisol and alpha-Amylase Secretion Patterns between and within Depressed and Non-Depressed Individuals

ObjectivesAssociations between biological stress markers and depression are inconsistent across studies. We assessed whether inter- and intra-individual variability explain these inconsistencies.MethodsPair-matched depressed and non-depressed participants (N = 30) collected saliva thrice a day for 30 days, resulting in 90 measurements per individual. The relationships between measures of stress-system function and depression were examined at the group level by means of mixed model analyses, and at the individual level by means of pair-matched comparisons. The analyses were repeated after adjusting for time-varying lifestyle factors by means of time-series regression analyses.ResultsCortisol and α-amylase levels were higher, the α-amylase/cortisol ratio larger, and the daily cortisol slope steeper in the depressed compared to the non-depressed group. Adjusting for lifestyle factors and antidepressant use reduced the associations under study. In 40%-60% of the matched comparisons, depressed individuals had higher cortisol and α-amylase levels, a larger α-amylase/cortisol ratio, and a steeper daily slope than their non-depressed match, regardless of adjustment.ConclusionsOur group-level findings were mostly in line with the literature but generalization to individuals appeared troublesome. Findings of studies on this topic should be interpreted with care, because in clinical practice the focus is on individuals instead of groups