Paul M. Stewart, Division of Medical Sciences, University of Birmingham, Birmingham B15 2TH, UK. Tel.: +44 121415 8708; Fax: +44 121415 8712; E-mail: [email protected]

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Summary

Background and aim The alcohol-induced pseudo-Cushing's syndrome is an important differential diagnosis of hypercortisolism that is poorly understood. Two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) interconvert hormonally active cortisol (F) and inactive cortisone (E). Previously we have shown higher urinary F : E metabolite ratios (a reflection of global 11β-HSD activity) in patients with alcoholic liver disease (ALD) compared to patients with chronic liver disease (CLD) of other aetiologies, suggesting that the phenotype of alcoholic pseudo-Cushing's may relate to altered metabolism of F.

Subjects and methods We performed selective venous sampling of the hepatic, renal and peripheral veins measuring F and E concentrations (using in-house radioimmunoassay) in 20 patients with histologically confirmed ALD and 19 patients with CLD. Six patients who also had selective venous sampling for investigation of suspected hyperaldosteronism were used as ‘normal’ controls.

Results There was a significant difference in the hepatic F gradient (mean ± SEM) between groups, indicating increased F production in the liver in patients with ALD (34·5 ± 21·7 nmol/l) compared to those with CLD (–21·0 ± 18·5 nmol/l) (P < 0·05) and normals (–19·7 ± 17·2 nmol/l) (P < 0·05). 11β-HSD1 mRNA expression was increased fivefold in the ALD group compared with normal controls (P < 0·01).

Conclusions These results indicate significant induction of HSD11B1 gene expression and activity in patients with ALD during short- and long-term abstinence from alcohol. The mechanism is unknown but might be explained on the basis of alcohol-induced changes in intracellular redox potential or as a protective mechanism to limit liver inflammation and injury. Selective 11β-HSD1 inhibitors may offer a novel therapeutic approach to treat alcoholic pseudo-Cushing's.

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Volume68, Issue6

June 2008

Pages 898-903

Induction of hepatic 11β-hydroxysteroid dehydrogenase type 1 in patients with alcoholic liver disease

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Induction of hepatic 11β-hydroxysteroid dehydrogenase type 1 in patients with alcoholic liver disease

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