Assessment of subtle changes in glucocorticoid negative feedback using prednisolone: comparison of salivary free cortisol and urinary cortisol metabolites as endpoints.
BACKGROUND
Prednisolone is better than dexamethasone to probe subtle changes in HPA axis sensitivity but cortisol assay as an endpoint risks cross-reaction with prednisolone. We compared capillary gas chromatography, which distinguishes urinary cortisol and prednisolone metabolites, and salivary cortisol immunoassay.


METHODS
Twenty adult volunteers (10 m) collected urine for consecutive 3 h periods and saliva at 3 h intervals from 2100 for 24 h, took prednisolone (5 mg) at midnight and continued collecting until 2100.


RESULTS
Suppression of urine cortisol metabolites began at 0600 and ceased after 1800. The lowest CV was obtained for the period 0900-1800: mean suppression was 56 +/- 7% for males and 55 +/- 9% for females. Suppression of salivary cortisol was only consistently seen at 0900: mean suppression was 41 +/- 5% in males and 47 +/- 9% in females. Chromatography revealed significant cross reactivity of prednisolone in saliva at 0300 and 0600, but not by 0900. Suppression of salivary cortisol and urinary cortisol metabolites was not correlated for either gender.


CONCLUSIONS
Both urinary cortisol metabolite and salivary cortisol assay following administration of 5 mg prednisolone have potential for investigation of changed HPA axis negative feedback, based on a convenient pre- and post-dose urinary collection between 0900 and 1800 and salivary sampling at 0900.
Jerjes
Walid K
WK
Department of Clinical Biochemistry, Guy's, King's and St. Thomas' School of Medicine, Bessemer Road, London SE5 9RS, UK. w_jerjes@yahoo.co.uk
Cleare
Anthony J
AJ
Wood
Peter J
PJ
Taylor
Norman F
NF
D000328:Adult; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm / Q000502:physiology; D005246:Feedback; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis* / Q000378:metabolism / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007118:Immunoassay; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology; D011239:Prednisolone / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D012463:Saliva / Q000737:chemistry* / Q000187:drug effects
D005938:Glucocorticoids; D011239:Prednisolone; D006854:Hydrocortisone