Scandinavian Journal of Gastroenterology. 2012; 47: 1030–1036 ORIGINAL ARTICLE The role of glucocorticoids in sodium retention in cirrhotic patients: A double blind, randomized, crossover study MARTIN HØJMARK HANSEN 1,3 , STEFFEN SKOTT KRISTENSEN 1,3 , OVE B. SCHAFFALITZKY DE MUCKADELL 1,3 , HELLE CHARLOTTE THIESSON 2,3 , RUTH ANDREW 4 & ANNETTE DAM FIALLA 1 1 Department of Medical Gastroenterology, Odense University Hospital, Odense C, Denmark, 2 Department of Medical Nephrology, Odense University Hospital, Odense C, Denmark, 3 University of Southern Denmark, Odense M, Denmark, and 4 Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK Abstract Objective. Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-b-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. Conclusion. These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver. Key Words: 11-b-hydroxysteroid dehydrogenase type 2, cirrhosis, cortisol, liver, mineralocorticoid receptor, sodium retention Introduction The prognosis of liver cirrhosis is poor, and is characterized by increased morbidity and mor- tality, with a 10-year relative survival of 34% [1]. Survival rate is lower if complications such as ascites, variceal bleeding or encephalopathy are present at the time of diagnosis [2]. A better under- standing of the pathophysiology leading to complica- tions may lead to an adequate and improved treatment [3]. According to the forward theory of ascites formation, a relative underfill of the central vascular compartment increases the activity of renin-angiotensin-aldosterone- system (RAAS) and other anti-natriuretic systems. This leads to increased water and sodium retention causing plasma volume expansion leading to ascites formation [4]. In addition a forward increase in splanchnic cap- illary pressure leads to increased lymph production which contributes to the ascites formation [3,5]. How- ever, not all cirrhotic patients have increased levels of aldosterone when accumulating ascites [6]. Correspondence: Ove B. Schaffalitzky de Muckadell, Afdeling for Medicinske Mavetarmsygdomme S, Odense Universitetshospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. E-mail: sdm@ouh.regionsyddanmark.dk Martin Højmark Hansen and Steffen Skott Kristensen contributed equally. (Received 27 February 2012; revised 18 April 2012; accepted 16 April 2012) ISSN 0036-5521 print/ISSN 1502-7708 online Ó 2012 Informa Healthcare DOI: 10.3109/00365521.2012.690044 Scand J Gastroenterol Downloaded from informahealthcare.com by University of Southern Denmark on 02/26/15 For personal use only.