Ahmed A et al. (2008) Induction of hepatic 11β-hydroxysteroid dehydrogenase type 1 in patients with alcoholic liver disease. Clin Endocrinol 68: 898–903

In vivo, type 1 11β-hydroxysteroid dehydrogenase converts inactive cortisone to active cortisol, primarily in the liver, whereas the type 2 isoenzyme catalyzes the reverse process, mainly in the kidney. Ahmed and colleagues previously reported that patients with alcoholic liver disease (ALD) had increased urinary ratios of cortisol to cortisone metabolites. These authors have now demonstrated that patients with alcohol-induced, pseudo-Cushing syndrome have normal secretion but aberrant metabolism of cortisol.

The study included 20 patients with histologically confirmed ALD, 19 with chronic nonalcoholic liver disease (NLD), and 6 otherwise healthy controls with presumed primary aldosteronism. Cortisol concentrations in hepatic venous blood were significantly higher in patients with ALD than in either patients with NLD or controls. However, there were no differences between groups with regard to renal function or renal-vein cortisone concentrations, which suggested that type 2 11β-hydroxysteroid dehydrogenase levels and activity were unaffected. In vitro studies suggested that upregulation of the type 1 isoenzyme rather than alteration of its activity caused the increased hepatic production of cortisol; in liver samples from a different cohort (seven patients with ALD, nine with NLD and six healthy individuals), expression of type 1 11β-hydroxysteroid dehydrogenase mRNA was fivefold greater in patients with ALD than in controls.

The researchers speculate that induction of the type 1 isoenzyme might protect against alcohol-induced hepatic injury. Generation of cortisol in the liver might dampen the inflammatory response and thus limit tissue damage.