Abstract
Abstract Introduction Sleep problems are associated with alterations in diurnal cortisol patterns, reflective of altered hypothalamic-pituitary-axis (HPA) activity. At-home collection of dried samples for measurement of urinary free cortisol are useful for assessment of diurnal rhythms because they do not impose the stress or sleep disruption associated with inpatient studies. The purpose of this analysis was to assess urinary cortisol responses among a large real-world dataset of at-home collection kit users and the potential for utility in identifying alterations in HPA-axis activity. Methods This retrospective analysis evaluated data from 3,966 individuals who used a Sleep and Stress Test (Everlywell, Inc.) between September 2017 and July 2021. Four dried urine spot samples were collected according to habitual sleep patterns: upon waking (T1), two hours after waking (T2), prior to the evening meal (T3), and at bedtime (T4). Urinary free cortisol normalized to creatinine, indicative of HPA-axis activity was assessed (area under the curve (AUC), wake to bedtime diurnal cortisol slope (DCS), mid-morning (T2) and bedtime (T4) cortisol levels). Sample reference ranges were established from two standard deviations above and below the log-transformed mean at each time point, values were reverted to original units for reporting. Results The sample was predominantly female (n=2,832, 71%). Mean age was 42.8 (sd=12.0) years. Seventy-eight individuals had mid-morning (T2) cortisol levels that were higher than the sample reference range (7.0-170.7 ug/g Cr), and 88 individuals below. Bedtime (T4) cortisol levels were elevated in 145 individuals (reference range 1.1-25.0 ug/g Cr). Total AUC for cortisol was high in 93 and low in 81 of individuals. The slope of the diurnal cortisol response was flattened in 20.6% (n=816) of the sample. Conclusion This real-world study demonstrates that at-home dried urine sample collection can be used to characterize normal and atypical HPA-axis activity. Convenient assessment of alterations in diurnal cortisol patterns are critical in identifying and understanding the mechanisms of HPA-axis activity common in sleep disruptions/disorders. Future studies utilizing this methodology may prove useful in identifying subpopulations with altered HPA-axis activity, sleep issues, and potential relationships to cardiometabolic health. Support (If Any)
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