Assessing adrenocortical activity by determining levels of urinary free cortisol and urinary 6 beta-hydroxycortisol

A comparative study of urinary free cortisol and urinary 6 beta-hydroxycortisol levels as a diagnostic test for hypercortisolemic states was carried out by measuring the excretion in 24-h specimens from 289 apparently healthy subjects and 10 Cushing patients. The diurnal variations of both variables were examined in normal subjects and subjects with altered adrenal activities. Two of the 289 apparently normal subjects had high values of urinary free cortisol; one had a high, the other a normal 6 beta-hydroxycortisol level; they were later diagnosed as having Cushing's syndrome and infertility, respectively. Three other subjects had high values of the urinary variables, but during 5 years of follow-up did not show any clinical evidence of hypercortisolism. The two urinary variables gave no false-negative results in the Cushing patients. The diurnal variation revealed that levels of 6 beta-hydroxycortisol change in parallel with those of free cortisol in normal subjects and in subjects with altered adrenal activities. However, the ratio of 6 beta-hydroxycortisol to free cortisol during the diurnal variation varied from low values when free cortisol levels were high to high values when free cortisol levels were low. In normal subjects, 1 mg of dexamethasone taken orally at 23.00 h completely suppressed the levels of both variables on the following day. It is concluded that urinary 6 beta-hydroxycortisol is correlated to urinary free cortisol so that measurement of urinary 6 beta-hydroxycortisol levels can be used as a diagnostic test for hypercortisolism in a way comparable to the method using urinary free cortisol.