Endocrine Abstracts

The pseudo-Cushing’s syndrome that accompanies both acute alcohol ingestion and alcohol withdrawal 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 total body 11βHSD activity) in patients with alcoholic liver disease (ALD) compared to patients with chronic liver disease (CLD) of other etiologies, suggesting that the phenotype of alcoholic pseudo-Cushing’s may relate to altered hepatic metabolism of F. We have further evaluated hepatic glucocorticoid metabolism by measuring F and E concentrations in the blood obtained simultaneously by selective venous sampling in the hepatic, portal, renal and peripheral veins. 20 patients with histologically confirmed ALD and 19 patients with CLD of other etiologies were admitted for transjugular liver biopsy or insertion of transjugular intrahepatic portosystemic shunt (TIPS) according to clinical indications. Serum F, and E was measured by in-house RIA in each vascular bed. 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). There was no significant difference in the renal E generation between groups (mean +/− SEM) (ALD, 14.3+/−3.9. CLD, 19.1+/−3.9), (P=0.4), eliminating differences in renal 11βHSD2 activity between groups. The hepatic vein F/E ratio was greater then the portal vein ratio (P<0.05) in six patients from both groups. The results indicate increased cortisol and F/E ratio in the hepatic vein in patients with ALD compared with patients with CLD, in keeping with increased hepatic cortisol generation via induction of 11βHSD1 oxo-reductase activity. The mechanism is unknown but might be explained on the basis of alcohol-induced changes in intracellular redox potential. Selective 11β-HSD1 inhibitors may offer a novel therapeutic approach to treat alcohol pseudo-Cushings.