Urine-free cortisol excretion: evidence of sex-dependence

Measurement of urine-free (unconjugated) cortisol (UFC) excretion is widely used in the investigation of hypercortisolaemia. We have measured 24 h UFC excretion in normal healthy individuals using a radioimmunoassay (RIA) method claimed to be suitable for unextracted urine. Significantly higher rates of excretion were found in a group of 15 men compared with a group of 18 women, with median values of 230 (range 145-334) and 149 (range 67-315) nmol/24 h, respectively (P < 0.005). This method was used to reanalyse the urine samples after extraction with dichloromethane. Although values were significantly lower than those found with unextracted urine (P < 0.001), the male:female difference remained with median values of 140 (range 96-295) and 112 (range 29-196) nmol/24 h, respectively (P < 0.02). Rates of UFC excretion were measured on the same dichloromethane-extracted urine samples using a second, different RIA, which again demonstrated the male:female difference with median values of 151 (range 116-302) and 109 (range 36-205) nmol/24 h, respectively (P < 0.001). There was no significant difference between these values and those obtained with extracted urine in the first assay. The higher rates of UFC excretion in men compared to women does not appear to be due to the presence of interfering compounds since the difference is also present using extracted urine samples and with two methods using different antibodies. These results should be borne in mind by laboratories when interpreting UFC results.