Cortisol metabolism in total extrahepatic biliary obstruction

The production and metabolism of cortisol in biliary obstruction have been studied by administration of iv tracers of ¹⁴C-cortisol to 3 patients with total extrahepatic biliary obstruction. The influence of ACTH on ¹⁴C-cortisol metabolism was also studied in 2 cirrhotics and 2 noncirrhotic patients. Results in the biliary obstruction patients were as follows: cortisol production was elevated (26-40 mg/g creatinine-normal 10-20); glucosiduronate formation was decreased (15-34% of the dose-normal 43-66%) to levels similar to those of cirrhotics; the ratio of cortolone (20α) to THE was increased to 3 times normal, an abnormality heretofore uniquely observed in cirrhosis. Certain differences of metabolite pattern between cirrhotics and patients with biliary obstruction (i.e., more THF, R-E and R-epi-E, and less cortolone, R-U and R-epi-U in the obstruction patients) appear to be due to increased cortisol production in obstruction patients, since administration of ACTH to cirrhotics changed their cortisol metabolite pattern so as to eliminate most of the differences between the 2 groups. The fact that biliary obstruction, alone among disease states studied to date, reproduces the key cortisol metabolism abnormality of cirrhosis, i.e., marked elevation of the cortolone/THE ratio, supports our earlier hypothesis (J Clin Endocr 28: 92, 1968) that abnormal cortisol metabolism in cirrhosis is due to cholestasis.