Interstitial cortisol measurements aligned by wake time, healthy volunteers

Background: Cortisol is released upon activation of the
hypothalamic-pituitary-adrenal axis, varies across the day, and possesses
an underlying diurnal rhythm reactive and responsive to stressors. While
the endogenous peak of cortisol occurs in the morning, the observed
cortisol rise post-awakening has been named the cortisol awakening
response (CAR) based on the belief that the act of waking up stimulates
cortisol secretion. However, objective evidence that awakening universally
induces cortisol secretion is limited. Methods: We used a mixed effects
model with a linear spline fitted to the data to examine tissue free
cortisol measurements obtained from 201 healthy volunteers by automated
ambulatory microdialysis before and after awakening in their home
environments. We also examined rate of change of cortisol depending on
sleep duration and relative timing. Results: We found no evidence for a
change in the rate of cortisol increase in the hour after waking when
compared with the hour prior to waking. We instead observed substantial
interindividual variability in absolute concentration and rate of change,
and differences in dynamics that may be attributable to duration and
relative timing of sleep. Conclusion: Based on these results, we strongly
suggest caution is needed when interpreting cortisol measurements solely
obtained in the hour after waking.