Hepato-Adrenal Syndrome in Decompensated Liver Cirrhosis Attenuated by Midodrine: A Proposed Mechanism in the Pathogenesis of Hepato-Adrenal Syndrome

Introduction: Increased portal venous resistance in cirrhosis leads to formation of porto-systemic shunts and splanchnic vasodilation. This is thought to be responsible for the hyperdynamic circulatory syndrome which is the pathogenetic basis for cirrhosis complications like ascites, gastroesophageal varices, and hepatorenal syndrome. We report a case of hepato-adrenal syndrome in a patient with decompensated cirrhosis. Case Description/Methods: A 70 year old male with history of Still’s disease and cryptogenic cirrhosis complicated by ascites and esophageal varices presented with worsening lower extremity edema, scrotal edema, abdominal distension for 6 months. Hospital course was complicated by refractory ascites requiring six large volume paracenteses, and variceal bleeding requiring multiple transfusions. Course further complicated by persistent hyponatremia and worsening renal failure concerning for hepato-renal syndrome. Hyponatremia did not improve with diuresis or oral urea supplementation. Morning cortisol and ACTH demonstrated evidence of adrenal insufficiency. Patient was started on midodrine. Both sodium level and GFR normalized. Cortisol level improved to three times its baseline, but subsequently decreased in the setting of missed midodrine dosing. Discussion: Recent evidence has demonstrated increased prevalence of relative adrenal insufficiency, coined hepato-adrenal syndrome, in stable, critically-ill, and post-liver transplant patients. There are several proposed mechanisms for the development of hepato-adrenal syndrome, including decreased ApoA1/HDL/LDL, endotoxemia, and adrenal gland structural damage. Treatment of adrenal insufficiency in cirrhosis remains controversial and there is inconsistent data regarding treatment for patients with cirrhosis without sepsis or septic shock. Treatment of hepatorenal syndrome with midodrine is well documented, and works by causing splanchnic vasoconstriction. We propose a mechanism in the pathogenesis of hepato-adrenal syndrome. Cirrhosis-mediated splanchnic vasodilation results in decreased effective circulating volume and organ perfusion leading to hepatorenal and hepato-adrenal syndrome. Midodrine, a potent splanchnic vasoconstrictor, increases effective circulating volume and organ perfusion resulting in improvement in renal and adrenal function, thus increasing sodium level, GFR, and cortisol levels as seen in this patient. Further studies are needed to compare treatment options in relative adrenal insufficiency in stable patients with cirrhosis.Table 1.: Effect of midodrine on blood pressure, sodium level, and AM cortisol.