Does adrenal insufficiency affect the liver?

From the Guidelines

Adrenal insufficiency can indeed affect the liver, and proper management with hormone replacement therapy is crucial to prevent liver-related complications and maintain normal liver function. Adrenal insufficiency, a condition where the adrenal glands don't produce enough cortisol and sometimes aldosterone, can impact liver function through several mechanisms. Cortisol plays an important role in glucose metabolism in the liver, helping to maintain blood sugar levels through gluconeogenesis. When cortisol is deficient, this can lead to hypoglycemia and altered liver metabolism, as noted in a study published in the Journal of Internal Medicine 1. Additionally, the chronic inflammation that may accompany untreated adrenal insufficiency can potentially affect liver function. In severe cases of adrenal crisis, reduced blood pressure and circulatory shock can cause decreased blood flow to the liver, resulting in liver damage.

Some key points to consider in the management of adrenal insufficiency and its impact on the liver include:

• The importance of hormone replacement therapy with glucocorticoids like hydrocortisone, typically 15-25 mg daily in divided doses, as well as mineralocorticoids like fludrocortisone, usually 0.05-0.2 mg daily, to prevent liver-related complications 1.
• The need for careful monitoring of patients with adrenal insufficiency, particularly in cases of acute decompensation of cirrhosis, where relative adrenal insufficiency is common and associated with higher mortality and complications 1.
• The potential benefits of hydrocortisone treatment in patients with refractory shock requiring high-dose vasopressors, as documented in the ADRENAL and APROCCHSS trials 1.

Overall, proper management of adrenal insufficiency with appropriate hormone replacement therapy is essential to prevent liver-related complications and maintain normal liver function, and healthcare providers should be aware of the potential impact of adrenal insufficiency on the liver in order to provide optimal care for their patients.

From the FDA Drug Label

Although there are a number of instances in which the synthesis of specific proteins is known to be induced by corticosteroids, the links between the initial actions of the hormones and the final metabolic effects have not been completely elucidated In larger doses, fludrocortisone acetate inhibits endogenous adrenal cortical secretion, thymic activity, and pituitary corticotropin excretion; promotes the deposition of liver glycogen; The answer is: Yes, adrenal insufficiency may affect the liver, as fludrocortisone acetate, which is used to treat adrenal insufficiency, promotes the deposition of liver glycogen in larger doses 2.

• Key points:
  • Fludrocortisone acetate affects liver glycogen deposition
  • Adrenal insufficiency treatment with fludrocortisone acetate may have an impact on liver metabolism
  • The exact mechanism of action is not fully understood, but it is known that fludrocortisone acetate has effects on electrolyte balance and carbohydrate metabolism 2

From the Research

Adrenal Insufficiency and Liver Disease

• Adrenal insufficiency is a common condition in patients with liver disease, particularly those with cirrhosis or liver failure 3, 4, 5.
• The term "hepato-adrenal syndrome" has been proposed to describe adrenal insufficiency in patients with advanced liver disease and sepsis or other complications 3, 5.
• Studies have shown that adrenal insufficiency is present in a significant proportion of patients with liver disease, including those with stable cirrhosis, decompensated cirrhosis, and liver transplant recipients 3, 4, 5.

Pathophysiology and Mechanisms

• The mechanisms of adrenal insufficiency in liver disease are not fully understood, but decreased levels of high-density lipoprotein cholesterol and high levels of proinflammatory cytokines and circulatory endotoxin have been suggested as potential contributing factors 3, 5.
• The prevalence of adrenal insufficiency in cirrhotic patients varies widely depending on the stage of liver disease, diagnostic criteria, and methodology used 4, 5.

Clinical Implications and Treatment

• Adrenal insufficiency in patients with liver disease may be associated with increased mortality, particularly in those with septic shock 3, 5.
• The effects of corticosteroid therapy on cirrhotic patients with septic shock and adrenal insufficiency are controversial, with some studies suggesting improved outcomes and others showing no benefit 4, 5.
• A case report has described a patient with acute liver failure due to adrenal insufficiency, highlighting the importance of considering adrenal insufficiency as a potential cause of liver disease 6.

Diagnosis and Assessment

• The diagnosis of adrenal insufficiency in patients with liver disease can be challenging, and there is no consensus on the appropriate tests and normal values to assess adrenal function 4.
• Serum total cortisol assays may overestimate adrenal insufficiency in patients with cirrhosis, and direct free cortisol measurement or its surrogates may be useful in defining adrenal insufficiency 4.