Altered pathways of urinary corticosteroid excretion in liver disease studied by a clinical laboratory method.

A method of sequential extraction of /3-glucuronidase-hydrolyzed urine, which permits the assessment of alternative pathways of corticosteroid excretion, was employedto study urine samplesfrom normal subjects and from patients with hepatic cirrhosis. In patients with hepatic cirrhosis there is a decrease in the excretion ef methylene dichloride-soluble 17-hydroxycorticosteroids; this decrease is due to significantly lower levels of tetrahydrocortisone, with moderately low levels of tetrahydrocortisol. A significant increase was observed in the levels of 17-OH,20,21glycols, confined mainly to cortols in the urine of patients with cirrhosis; a less marked increasein this fraction was also observed in patients with fatty metamorphosis of the liver. Urinary 17-ketosteroids were decreased in patients with hepatic cirrhosis.The intravenous infusion of adrenocorticotropin to normal subjects was followed by increased 17-hydroxycorticosteroidsin all solvent fractions of the urine. In patients with hepatic cirrhosis similarly treated, there was no significant rise in the level of 17-hydroxycorticosteroidsextracted with methylene dichloride, but significant increasesin polar 17-hydroxycorticosteroidswere found. The relative magnitudesof the alternate pathways of corticosteroid excretion were determined by calculation of the ratios of (1) total ketols to total glycols, (2) polar ketols to total glycols,and (3) less polar ketols to polar ketols; it was shown that in hepatic cirrhosis there are significant alterations in the excretory pathways of cortisol metabolites, with relative decreases in the excretion as tetrahydrocortisone and increasesin the excretion as cortols. Basedon these data it is clear that values of routine 17-hydroxycorticosteroidand 17-ketosteroid excretion should be evaluated carefully as to whether they represent abnormal adrenal function or alterations in the peripheral metabolism of cortisol. The method is sufficiently simple to be employed in the clinical laboratory.