Endocrine Abstracts (2015) 37 OC9.3 | DOI: 10.1530/endoabs.37.OC9.3

Modelling the salivary cortisone to serum cortisol inter-relationship to predict serum cortisol under physiological conditions and after hydrocortisone

Miguel Debono1, Robert Harrison1, Brian Keevil2, Martin Whitaker3, Dena Digweed3, Wiebke Arlt3,4 & Richard Ross1,3

1University of Sheffield, Sheffield, UK; 2University of Manchester, Manchester, UK; 3Diurnal Limited, Cardiff, UK; 4University of Birmingham, Birmingham, UK.

Introduction: Measuring serum cortisol to evaluate the normal circadian rhythm and adequacy of hydrocortisone replacement levels requires multiple readings; an expensive, cumbersome process. Conversely, salivary cortisone, a surrogate marker for free cortisol levels is non-invasive and well suited for out-patient settings. We hypothesised that salivary cortisone predicts circulating cortisol levels and can be used as an alternative marker of serum cortisol in a physiological setting or in patients on hydrocortisone replacement.

Methods: This was an observational study in 14 healthy male volunteers who had hourly serum cortisol measurements over 24 h in addition to salivary cortisol and cortisone measurements from 1500 h to 2200 h and from 0700 h to 1500 h; all measurements were carried out by liquid chromatography/tandem mass spectrometry. Relationships between serum and salivary cortisol/cortisone were assessed by individual correlation analysis and linear mixed effects modelling. A similar analysis was carried out after 20mg of oral and i.v. hydrocortisone given on different days after dexamethasone suppression.

Results: Correlation analysis (ρ), for the relationship between endogenous log-transformed salivary cortisone or salivary cortisol with serum cortisol rhythm, ranged from 0.96 to 0.99; P<0.001 and from 0.84 to 0.99; P<0.001, respectively. Salivary cortisone was superior to salivary cortisol (range R2: 0.93–0.99 vs 0.71–0.97) in predicting circulating, serum cortisol. By fitting a mixed effects model to predict serum cortisol levels from salivary cortisone (predicted serum cortisol (nmol/l)=(13.57+individual-specific random effects)×salivary cortisone (nmol/l)) correlation ρ and R2 between measured and predicted serum cortisol were 0.91 and 0.82 under physiological conditions, 0.89 and 0.66 for 20 mg oral hydrocortisone and 0.93 and 0.72 for 20 mg i.v. hydrocortisone, respectively.

Conclusion: Salivary cortisone levels are strongly related to serum cortisol and repetitive measurements of salivary cortisone may be used to predict the serum cortisol rhythm and cortisol levels after hydrocortisone.

Disclosure: This work was supported by the European Commission (HEALTH-FP7; Project No: 281654).

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