Salivary Cortisol is a reliable marker to monitor Hydrocortisone replacement

Bharat Pahilwani1, Sarah Darch2, Radha Ramachandran1, Jaimini Cegla1, Monica Nijher1, Karim Meeran1, Richard Chapman2, Mandy Donaldson2 and Tricia Tan1
1Department of Investigative Medicine, Charing Cross and Hammersmith Hospitals, Imperial College London, UK.

2Department of Clinical Biochemistry, Imperial College Healthcare NHS Trust, UK


Context: Hydrocortisone day curves (HCDC) are used to monitor hydrocortisone replacement by obtaining serum samples to measure cortisol levels throughout the day.  Salivary measurement of free cortisol offers a non-invasive alternative to serum measurements.


Objective: To validate salivary cortisol measurement as an alternative method to assess the adequacy of hydrocortisone replacement in patients with hypoadrenalism.


Setting, Patients, and Design: Dual-centre cross-sectional study of 23 patients, taking

hydrocortisone for hypoadrenalism and admitted for a HCDC to day-case clinical investigation centres in two referral hospitals (09/H0711/7). Simultaneous blood and saliva samples were obtained to determine total and free cortisol, respectively.

Outcome measures: Serum free cortisol was estimated using measurements of total serum cortisol,corticosteroid-binding globulin, albumin and previously validated mass-action formulae. Salivary cortisol levels were also measured in 24 healthy volunteers to determine a control profile.

Results: Serum total and salivary free cortisol correlated well (Spearman r=0.850, p<0.0001).  Salivary free cortisol correlated well with estimated serum free cortisol calculated by the Coolens formula (r=0.8764, p<0.0001) and the Dorin formula (r=0.8635, p<0.0001). Salivary cortisol measurements were significantly higher in patients than controls in the samples taken after doses of hydrocortisone but not significantly different in the samples taken before doses of hydrocortisone.

Conclusion: Salivary cortisol measurements offer a more cost-effective, non-invasive and well tolerated alternative to serum cortisol during HCDC.