From the Guidelines
Low cortisol levels are not a direct cause of elevated liver function tests, and other underlying causes should be investigated if liver enzyme elevations are present. Cortisol is a hormone produced by the adrenal glands that helps regulate metabolism, immune response, and stress. While cortisol does interact with the liver, insufficient cortisol (as seen in conditions like adrenal insufficiency or Addison's disease) generally doesn't lead to liver enzyme elevations. According to a consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1, increased liver transaminases may be present in some patients, but this is not a direct result of low cortisol levels.
Some key points to consider when evaluating the relationship between low cortisol and liver function tests include:
- The diagnosis of primary adrenal insufficiency requires assessing adrenal cortex function and establishing the etiology 1
- Laboratory findings such as hyponatremia, hyperkalemia, and increased liver transaminases may be present, but are not reliable markers for making a diagnosis 1
- Other causes of elevated liver function tests, such as medications, alcohol use, viral hepatitis, fatty liver disease, or other liver disorders, should be investigated
- Treatment for low cortisol, which typically involves cortisol replacement therapy like hydrocortisone, can help normalize any metabolic abnormalities that might be indirectly affecting liver values.
In some cases, patients with primary adrenal insufficiency may present with mild or moderate hypercalcaemia, anaemia, mild eosinophilia, lymphocytosis, and increased liver transaminases 1. However, these findings are not directly caused by low cortisol levels, and a thorough medical evaluation is necessary to determine the underlying causes of both low cortisol and abnormal liver tests.
From the Research
Relationship Between Cortisol and Liver Function
- The relationship between cortisol levels and liver function is complex, and research has yielded mixed results 2, 3, 4.
- Some studies suggest that low cortisol levels may be associated with liver disease, particularly in patients with cirrhosis 2, 4.
- However, other studies have found that the diagnosis of adrenal insufficiency using total cortisol is not confirmed using free cortisol, and that free cortisol is not associated with renal or cardiac dysfunction 3.
Cortisol and Liver Function Tests
- There is limited research on the direct relationship between low cortisol levels and elevated liver function tests.
- One study found that patients with higher Child-Pugh class had progressively lower free cortisol, suggesting a possible link between liver disease severity and cortisol levels 3.
- Another study found that relative adrenal insufficiency was associated with a high risk of developing sepsis, septic shock, organ failure, and death within 90 days in patients with cirrhosis 4.
Diagnostic Considerations
- The diagnosis of adrenal insufficiency can be challenging, particularly in patients with liver disease 2, 3, 5, 6.
- Different diagnostic tests, such as the insulin tolerance test and morning serum cortisol level, may be used to diagnose adrenal insufficiency 5.
- The use of free cortisol assays, such as liquid chromatography tandem mass spectrometry, may be helpful in diagnosing adrenal insufficiency in patients with binding globulin derangements 6.