Adrenocortical dysfunction in liver disease: A systematic review

Abstract

In patients with cirrhosis, adrenal insufficiency (AI) is reported during sepsis and septic shock and is associated with increased mortality. Consequently, the term “hepato‐adrenal syndrome” was proposed. Some studies have shown that AI is frequent in stable cirrhosis as well as in cirrhosis associated with decompensation other than sepsis, such as bleeding and ascites. Moreover, other studies showed a high prevalence in liver transplant recipients immediately after, or some time after, liver transplantation. The effect of corticosteroid therapy in critically ill patients with liver disease has been evaluated in some studies, but the results remain controversial. The 250‐μg adreno‐cortico‐tropic‐hormone stimulation test to diagnose AI in critically ill adult patients is recommended by an international task force. However, in liver disease, there is no consensus on the appropriate tests and normal values to assess adrenal function; thus, standardization of normal ranges and methodology is needed. Serum total cortisol assays overestimate AI in patients with cirrhosis, so that direct free cortisol measurement or its surrogates may be useful measurements to define AI, but further studies are needed to clarify this. In addition, the mechanisms by which liver disease leads to adrenal dysfunction are not sufficiently documented. This review evaluates published data regarding adrenal function in patients with liver disease, with a particular focus on the potential limitations of these studies as well as suggestions for future studies. (HEPATOLOGY 2012)

FGF21 Maintains Glucose Homeostasis by Mediating the Cross Talk Between Liver and Brain During Prolonged Fasting

“…This novel liver-PPARa-FGF21-braincorticosterone circuit can fine tune the cross talk between brain and liver to avoid hypoglycemia during nutrient deprivation or other adverse clinical events. Interestingly, a novel "hepato-adrenal syndrome" has recently been suggested, demonstrating a defect in HPA activation in patients with severe liver disease (38). Hypoglycemia is a common clinical problem in patients with a defect in HPA regulation such as hypopituitarism and Addison disease.…”

Infections in Liver Disease

“…49 In a recent study, low cortisol level was associated with impairments of circulatory and renal function, higher likelihood of development of severe sepsis and type I HRS, as well as higher short-term mortality. 50 Although the occurrence of relative adrenal insufficiency appears to be exaggerated in patients with cirrhosis and septic shock, whether replacement doses of hydrocortisone affect outcome remains unknown.…”

Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis

“…RAI is frequent (51%-77%) in decompensated cirrhosis with severe sepsis or septic shock [107,108], but also occurs in 7-49% of non-critically ill patients [109,110]. However, other factors, like liver failure and systemic inflammation are likely involved as both impaired cholesterol synthesis and enhanced pro-inflammatory cytokine production can reduce adrenal steroidogenesis [111]. Adrenal dysfunction attenuates the vascular effect of angiotensin-II, norepinephrine and vasopressin in decompensated cirrhosis, further activating sympathetic tone [110].…”