Does methimazole affect the liver?

Methimazole's Effects on the Liver

Methimazole can affect the liver, but the risk of hepatotoxicity is lower compared to propylthiouracil (PTU), making it the preferred antithyroid medication during the second and third trimesters of pregnancy and for general treatment of hyperthyroidism. 1, 2

Hepatic Effects of Methimazole

Risk Profile

• Methimazole can cause hepatotoxicity, but the incidence is relatively low
• The FDA label specifically states that "although there have been reports of hepatotoxicity (including acute liver failure) associated with methimazole, the risk of hepatotoxicity appears to be less with methimazole than with propylthiouracil, especially in the pediatric population" 2
• In most cases, liver function abnormalities are mild and transient 3

Types of Liver Injury

• Methimazole can cause:
  • Drug-induced hepatitis
  • Cholestatic hepatitis (less common but reported in case studies) 4
  • Acute liver failure (rare) 2

Monitoring and Detection

• Signs of hepatic dysfunction that should prompt evaluation include:

  • Anorexia
  • Pruritus
  • Right upper quadrant pain
  • Jaundice (scleral icterus)
  • Dark urine 2, 4

• Laboratory monitoring:

  • Liver function tests (bilirubin, alkaline phosphatase, ALT, AST)
  • Drug treatment should be discontinued promptly if hepatic transaminase values exceed 3 times the upper limit of normal 2

Mechanisms of Methimazole-Induced Liver Injury

The exact mechanisms of methimazole-induced hepatotoxicity are not fully understood, but several pathways have been proposed:

1. Reactive metabolite formation - Methimazole can be metabolized to reactive intermediates that may bind to cellular proteins 5

2. Immune-mediated toxicity - Many cases appear to be idiosyncratic and immune-mediated 5

3. Oxidative stress - May contribute to hepatocellular damage in hyperthyroid patients 6

Clinical Course and Management

Baseline Liver Function

• Interestingly, hyperthyroidism itself can cause abnormal liver function tests in approximately 32.5% of patients before treatment 3
• In most patients with baseline abnormal liver function tests, methimazole treatment actually results in normalization of serum ALT and AST 3

During Treatment

• Mild elevations (<2× the upper limit of normal) may occur during treatment but are usually not clinically significant 3
• Severe hepatotoxicity is rare but can occur

Management of Hepatotoxicity

• If signs of liver dysfunction develop, promptly evaluate liver function
• Discontinue methimazole if clinically significant evidence of liver abnormality is found, particularly if transaminases exceed 3× upper limit of normal 2
• Consider alternative treatments for hyperthyroidism if hepatotoxicity occurs

Risk Factors for Hepatotoxicity

Several factors may increase susceptibility to methimazole-induced liver injury:

• Age
• Gender
• Metabolism characteristics
• Alcohol consumption
• Underlying liver diseases
• Immunologic mechanisms
• Drug interactions 7

Clinical Recommendations

1. Baseline Assessment: Obtain liver function tests before initiating methimazole therapy

2. Patient Education: Inform patients about potential signs of hepatotoxicity and when to seek medical attention

3. Regular Monitoring: Monitor liver function periodically during treatment, especially in the first few months

4. Prompt Discontinuation: If significant liver abnormalities develop, discontinue methimazole and consider alternative treatments

5. Alternative Options: Consider radioactive iodine or surgery if methimazole causes hepatotoxicity (except in pregnancy, where radioactive iodine is contraindicated) 1

While methimazole can affect the liver, its hepatotoxicity risk is generally lower than propylthiouracil, making it the preferred antithyroid medication in most clinical scenarios except during the first trimester of pregnancy.