Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone (#111)
Objective, Design, Subjects: Optimal method for monitoring oral hydrocortisone replacement therapy has not been established, and there are few data on cortisol levels following intravenous hydrocortisone given at “stress” doses. Cortisol profiles were measured in plasma, saliva and urine following physiological (20 mg oral) or stress (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to their endogenous cortisol levels.
Measurements: Plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5h, and hourly from time 0 to 5h following administration of oral or intravenous hydrocortisone.
Results: After oral hydrocortisone administration, the measurement of plasma, salivary or urine cortisol at 2h post-dose gave a good indication of peak cortisol concentrations, which were supraphysiological. The correlation between plasma and salivary cortisol concentrations after oral hydrocortisone (R = 0.83) was stronger than that using endogenous concentrations (R = 0.62), whereas plasma-urine cortisol relationship was similar (R = 0.61, compared to endogenous R = 0.56). Intravenous hydrocortisone administration achieved very high peak cortisol levels and strong correlations between plasma and saliva (R = 0.94) and urine cortisol (R = 0.82) levels were observed. Cortisol clearance was significantly higher following intravenous compared to oral administration. There was no difference in CBG levels during the sampling period.
Conclusion: Based on the cortisol levels achieved, an oral dose of hydrocortisone 20 mg is excessive for routine maintenance, while stress doses above 50 mg 6-hourly are rarely necessary in acute cortisol deficiency. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.