Can carbimazole (antithyroid medication) worsen transaminitis (elevated liver enzymes)?

Carbimazole Can Worsen Transaminitis

Yes, carbimazole can worsen transaminitis and cause hepatotoxicity ranging from mild transaminase elevation to severe liver injury. 1

Hepatotoxicity Profile of Carbimazole

• Carbimazole can cause asymptomatic transient increases in liver enzymes or severe liver injury with either cholestatic or hepatocellular patterns 2
• Hepatotoxicity is a rare but serious side effect of carbimazole therapy 3
• Clinical studies have documented cases of severe hepatotoxicity requiring discontinuation of carbimazole 4, 5
• In a systematic review of antithyroid drug-related liver injury, carbimazole/methimazole was found to be the most common offending agent (55.7% of cases) 1

Clinical Presentation and Patterns of Liver Injury

• Liver injury from carbimazole can present as:
  • Hepatocellular pattern (41.8% of cases) 1
  • Cholestatic pattern (41.3% of cases) 1
  • Mixed pattern (16.9% of cases) 1
• Clinical manifestations may include jaundice, pruritus, abdominal pain, and elevated liver enzymes 3, 5
• Severe cases can progress to liver failure requiring transplantation (6.4% of cases) 1

Monitoring Recommendations

• Baseline liver function tests should be obtained before initiating carbimazole therapy, especially in patients with pre-existing liver disease 6
• Regular monitoring of liver function is recommended during carbimazole treatment 4
• If transaminases exceed three times the upper limit of normal with symptoms or five times the upper limit of normal without symptoms, consider withholding carbimazole 6
• Patients should be educated about symptoms of hepatotoxicity (jaundice, abdominal pain, malaise) and instructed to seek immediate medical attention if these develop 2

Management of Carbimazole-Induced Hepatotoxicity

• Discontinue carbimazole immediately if significant hepatotoxicity is suspected 3, 5
• After discontinuation, liver function tests typically normalize within 4-12 weeks 3
• Alternative treatment options for hyperthyroidism in patients with carbimazole-induced hepatotoxicity include:
  • Radioactive iodine therapy 3
  • Surgical thyroidectomy 3
  • In some cases, switching to propylthiouracil may be considered, though cross-reactivity can occur 3, 2

Risk Factors for Hepatotoxicity

• Advanced age 2
• Higher doses of carbimazole 2, 4
• Pre-existing liver disease 6
• Concomitant use of other hepatotoxic medications 6

Clinical Implications

• Hepatotoxicity from carbimazole is generally reversible upon discontinuation, with complete resolution in approximately 80% of cases 1
• Mortality has been reported in 11.8% of cases of antithyroid drug-induced liver injury 1
• The median time to resolution of liver injury after discontinuation is approximately 45 days 1
• Rechallenge with carbimazole after hepatotoxicity is generally not recommended due to risk of recurrence, though limited data suggests it may be successful in some cases 1

Comparison with Other Antithyroid Drugs

• Propylthiouracil (PTU) may cause more severe hepatotoxicity compared to carbimazole/methimazole, with higher rates of mortality and need for liver transplantation 1
• Switching between carbimazole and methimazole should not be considered in case of side effects as carbimazole is rapidly metabolized to methimazole 2
• Cross-reactivity between thioimidazoles (carbimazole/methimazole) and propylthiouracil can occur, though the mechanism of liver injury differs between these drug classes 3, 2