Endocrine Abstracts

For investigation of mild glucocorticoid resistance, dexamethasone may be inappropriate because, unlike cortisol, it crosses the blood-brain barrier and suitably low doses are difficult to titrate. Prednisolone has been proposed as an alternative but assay of cortisol as an endpoint is subject to cross-reaction with prednisolone in most ligand assays. Using capillary gas chromatography, we can distinguish urinary cortisol and prednisolone metabolites. We have compared this approach with salivary cortisol immunoassay. Adult volunteers (10 m, 10 f) collected urine for consecutive 3h periods and saliva at 3h intervals for 24h (Day 1). Prednisolone (5mg) was taken at midnight on Day 1. They continued collecting for 24h. Percent suppression pre-post treatment was calculated for each period. Suppression of urine cortisol metabolites was seen in all individuals from 0600 until 1800. Comparing the inter-individual variability for periods over this time, the coefficients of variation (CV) ranged from (m & f) 26 - 50 & 39-49 percent. The lowest CV was obtained for the combined period 0900-1800: 23 & 30 percent, with mean suppression 58 & 55 percent. Suppression of salivary cortisol was only seen in every individual at 0900 and the mean suppression was 41 & 65 percent. Suppression of salivary cortisol and urinary cortisol metabolites was not significantly correlated. The variable suppression noted from the immunoassay data may be attributed to cross reaction with prednisolone or its metabolites: excretion of these in urine continued for up to 18h post dose and did not show simple kinetics.
We conclude that urinary cortisol metabolite assay in conjunction with administration of 5 mg prednisolone is appropriate for investigation of mild glucocorticoid resistance, based on a convenient pre and post dose 0900-1800 collection. Use of immunoassay on salivary samples merits careful evaluation.