Can Oral Hydrocortisone Cause Elevated LFTs?
Yes, oral hydrocortisone can cause elevated liver function tests, though this is uncommon and typically occurs through indirect metabolic effects rather than direct hepatotoxicity.
Mechanism and Clinical Evidence
Hydrocortisone and other corticosteroids can elevate LFTs through several pathways:
Metabolic effects: Corticosteroids induce insulin resistance and promote hepatic steatosis (fatty liver), which secondarily elevates transaminases 1. In patients with secondary adrenal insufficiency on conventional hydrocortisone, hepatic steatosis was documented in 68.8% by ultrasonography, with the hydrocortisone dose being an independent predictor of hepatic steatosis index 1.
Direct hepatotoxicity (rare): While uncommon, corticosteroids can rarely cause direct drug-induced liver injury. A case report documented acute liver failure with AST 18,000 U/L and ALT 12,000 U/L following prednisolone administration, requiring plasma exchange 2. This represents an idiosyncratic reaction rather than dose-dependent toxicity.
Oxidative stress: Animal studies demonstrate that hydrocortisone induces hepatic oxidative stress with significant elevations in ALT and AST, accompanied by destruction of normal hepatic architecture 3.
Clinical Context and Differential Diagnosis
When evaluating elevated LFTs in a patient on oral hydrocortisone, you must systematically exclude more common causes before attributing the elevation to the corticosteroid 4:
- Viral hepatitis (hepatitis A, B, C, E)
- Alcohol consumption
- Other hepatotoxic medications
- Underlying liver disease (NAFLD, autoimmune hepatitis)
- Biliary obstruction
The temporal relationship between drug initiation and LFT elevation is critical for causality assessment 4.
Management Approach
For mild elevations (ALT 1-3x ULN):
- Monitor LFTs weekly to biweekly 5
- Obtain detailed medication history including over-the-counter products and supplements 5
- Continue hydrocortisone with close observation if clinically necessary
For moderate elevations (ALT 3-5x ULN):
- Repeat LFTs within 2-3 days 5
- Consider temporarily holding or reducing the hydrocortisone dose if clinically feasible 6
- Initiate workup for alternative causes including viral serologies, autoimmune markers (ANA, ASMA), and hepatobiliary imaging 5
For severe elevations (ALT >5x ULN):
- Discontinue hydrocortisone immediately 5
- Repeat LFTs within 2-3 days and monitor 2-3 times weekly 5
- Comprehensive evaluation including hepatology consultation 5
- Consider liver biopsy if diagnosis remains unclear or patient fails to improve 5
Important Caveats
Paradoxical use: Corticosteroids like prednisolone and methylprednisolone are actually the treatment for immune-mediated liver injury from other causes (such as checkpoint inhibitor hepatotoxicity), typically at doses of 0.5-2 mg/kg/day 5. This creates a clinical paradox where corticosteroids both treat and (rarely) cause liver injury.
Dose considerations: In patients with chronic liver disease, corticosteroid metabolism is impaired and protein binding is reduced, leading to elevated free cortisol levels 7. These patients may require lower doses and exhibit increased sensitivity to corticosteroid effects 7.
Pattern recognition: Corticosteroid-induced LFT elevation typically shows a hepatocellular pattern (elevated ALT/AST) rather than cholestatic pattern 3. The presence of metabolic syndrome features (obesity, insulin resistance) suggests steatosis as the mechanism 1.
The key clinical principle: While hydrocortisone can elevate LFTs, this is sufficiently uncommon that other causes must be rigorously excluded before attributing the abnormality to the corticosteroid itself 4.