Cortisone (S5) - Bedtime

This sample measures cortisone in your saliva at bedtime, the final time point of the day. Like cortisol, cortisone should be near its lowest level at this point. Because salivary cortisone correlates with blood free cortisol better than salivary cortisol does, this reading may be the most reliable salivary indicator of whether your circulating cortisol has truly reached its nighttime floor.

This time point is particularly useful as a check against hydrocortisone cream contamination. Hydrocortisone is bioidentical to active cortisol. If even a trace of it is on your hands or near your mouth when you collect the bedtime sample, it will elevate cortisol but not cortisone, because cortisol must enter the body in order to be deactivated to cortisone. If your bedtime cortisol is much higher than your bedtime cortisone, contamination may be the cause, and the cortisone pattern becomes the more accurate representation of your HPA axis function at that time.

Confirming the Bedtime Picture

When bedtime cortisol and cortisone both match (both near zero, or both elevated), they confirm each other. In particular, when both are elevated at bedtime with no normal daily rhythm, and metabolized cortisol is also high, further evaluation for cortisol excess conditions such as Cushing's disease may be warranted. In Cushing's, bedtime cortisol is often more than four times above the upper reference range limit.

When cortisol appears low at bedtime but cortisone is relatively higher, it may suggest that the 11b-HSD2 enzyme in the salivary glands is particularly active, converting cortisol to cortisone before it reaches your sample. In this case, your true circulating cortisol may be somewhat higher than the cortisol reading alone implies. Similarly, low or flat cortisol throughout the day confirmed by low or flat cortisone throughout the day strengthens the interpretation that total daily cortisol output is genuinely low.

Questions This Biomarker Can Answer

• Has my cortisone reached its expected nighttime low, confirming that cortisol has settled?
• Could a mismatch between bedtime cortisol and cortisone indicate sample contamination from hydrocortisone cream?
• Does elevated bedtime cortisone, alongside elevated bedtime cortisol, suggest a pattern worth further clinical evaluation?