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Interstitial cortisol measurements aligned by wake time, healthy volunteers

Klaas, Samantha1; Upton, Thomas1; Zavala, Eder2; Lawton, Michael1; Bensing, Sophie3; Berinder, Katarina3; Botusan, Ileana3; Grytaas, Marianne4; Methlie, Paal5; Øksnes, Marianne5; Russell, Georgina1; Vassiliadi, Dimitra6; Lightman, Stafford1

Published Nov 24, 2024 on Dryad. https://doi.org/10.5061/dryad.2280gb62w

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Abstract

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.