The role of glucocorticoids in sodium retention in cirrhotic patients: a double blind, randomized, crossover study.
OBJECTIVE
Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-β-hydroxysteroid dehydrogenase type-2 activity. This suggests that cortisol--by activation of the mineralocorticoid receptor--may contribute to the abnormal sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients.


METHODS
A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout interval of 14 days separated the two periods. After a basal period of 36 h, dexamethasone (0.5 mg every 6 h) or placebo was given for two days. Urine was collected for 12 h periods, and the concentrations of sodium, potassium, creatinine, cortisol and cortisol metabolites were determined. Blood samples for hemoglobin, glucose, sodium, potassium, creatinine, aldosterone and cortisol were obtained daily.


RESULTS
Dexamethasone treatment decreased S-cortisol 92.3% (82.9-93.4%) (median and range) compared with that in the basal period. Natriuresis (dexamethasone--placebo) increased 55.1 (-26.4-168.7) mmol/day (median and range). No statistically significant differences (dexamethasone--placebo) were found in changes in body weight (0.00 (-0.45-2.20) kg/day), diuresis (0.56 (-0.35-1.43) L/day) or mean arterial pressure (8.33 (-16.0-41.3) mmHg) (median and range) in reference to the preceding 24 h basal period.


CONCLUSIONS
These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver.
Department of Medical Gastroenterology, Odense University Hospital, Odense C, Denmark.
Martin
M
Højmark Hansen
Steffen Skott
SS
Kristensen
Ove B
OB
Schaffalitzky de Muckadell
Helle Charlotte
HC
Thiesson
Ruth
R
Andrew
Annette
A
Dam Fialla
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004231:Diuresis / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000097:blood / Q000652:urine; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D006454:Hemoglobins; D000450:Aldosterone; D003907:Dexamethasone; D012964:Sodium; D003404:Creatinine; D011188:Potassium; D006854:Hydrocortisone