Salivary cortisone reflects cortisol exposure under physiological conditions and after hydrocortisone

Measuring serum cortisol to evaluate stress, adrenal disease, and monitor hydrocortisone replacement requires venepuncture. Conversely, salivary measurements are non-invasive.

To investigate measurement of salivary cortisol and cortisone as alternatives to serum cortisol.

A prospective cross-over study in a Clinical Research Facility. Participants & method: Over 3 periods (period 1: 24h physiological cortisol rhythm; periods 2 and 3: after 20mg oral and intravenous hydrocortisone) 14 male volunteers had serum and saliva cortisol and cortisone, serum albumin, CBG, and free cortisol measured. Data were analysed for rhythm parameters and correlations. Linear mixed effects modelling was performed to determine the relationship between serum cortisol and salivary cortisone.

Serum cortisol and cortisone showed similar circadian rhythms with large peak:trough ratios (cortisol median ratio 11). Albumin and CBG showed minor peak:trough ratios <1. 2. When serum cortisol was <74 (SD 29) nmol/L, salivary cortisol was not detectable but salivary cortisone was always detected. Salivary cortisol post-oral hydrocortisone produced spurious results due to contamination. Under physiological conditions, salivary cortisone correlated strongly with serum cortisol [ρ (95%CI): 0. 91 (0. 89-0. 93);P<0. 001]. Similarly, following intravenous or oral hydrocortisone, salivary cortisone correlated strongly with serum cortisol [ρ (95% CI) = 0. 91 (0. 89-0. 92); P<0. 001]. A mixed effects model showed that in this population 94% of the variation in salivary cortisone could be predicted from serum cortisol.

Salivary cortisol is frequently undetectable and contaminated by oral hydrocortisone. In contrast, salivary cortisone reflects serum cortisol and provides a non-invasive alternative to measuring serum cortisol levels.

The Journal of clinical endocrinology and metabolism. 2016 Jan 26 [Epub ahead of print]

Miguel Debono, Robert F Harrison, Martin J Whitaker, David Eckland, Wiebke Arlt, Brian G Keevil, Richard J Ross

The University of Sheffield, Sheffield, UK;, The University of Sheffield, Sheffield, UK;, The University of Sheffield, Sheffield, UK;, Diurnal Limited, Cardiff, UK;, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, UK;, Department of Clinical Biochemistry, University Hospital S Manchester, Manchester, UK. , The University of Sheffield, Sheffield, UK;

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