What to do if a patient develops elevated liver enzymes (AST 60, ALT 136) after starting methimazole (Generic: Methimazole) 10 mg tid for new onset Grave's disease with normal baseline Liver Function Tests (LFTs) and initial Thyroid-Stimulating Hormone (TSH) less than 0.005 and free T4 6.4?

Management of Elevated Liver Enzymes After Starting Methimazole for Grave's Disease

Methimazole should be discontinued immediately due to the significant elevation in liver enzymes (ALT 136, AST 60) from normal baseline, as this represents likely drug-induced liver injury (DILI). 1

Assessment of Liver Enzyme Elevation

The patient's presentation shows:

• AST 60 and ALT 136 (elevated from normal baseline)
• Started on methimazole 10 mg TID for Grave's disease
• Initial TSH <0.005 and free T4 6.4 (indicating severe hyperthyroidism)

This pattern represents:

• Predominantly hepatocellular pattern of injury (ALT>AST)
• ALT elevation >3× upper limit of normal (ULN)
• Timing consistent with drug-induced liver injury (DILI)

Management Algorithm

1. Immediate Actions:

   • Discontinue methimazole immediately
   • Obtain additional liver function tests including:
     • Total and direct bilirubin
     • Alkaline phosphatase
     • INR
     • Albumin

2. Monitoring:

   • Repeat liver function tests within 7-10 days to assess trend
   • Monitor for symptoms of hepatotoxicity:
     • Right upper quadrant pain
     • Jaundice
     • Pruritus
     • Nausea/vomiting
     • Fatigue

3. Alternative Treatment Options for Hyperthyroidism:

   • Consider radioactive iodine therapy as preferred alternative
   • If medication is necessary, consider propylthiouracil (PTU) with caution
   • Beta-blockers for symptom control during transition
   • Consider surgical thyroidectomy if other options not suitable

Rationale for Discontinuation

The FDA label for methimazole clearly states that "drug treatment should be discontinued promptly in the event of clinically significant evidence of liver abnormality including hepatic transaminase values exceeding 3 times the upper limit of normal." 1 The patient's ALT of 136 significantly exceeds this threshold from a normal baseline.

While some studies suggest that mild LFT elevations during methimazole treatment can normalize despite continued therapy 2, the magnitude of elevation in this case (particularly ALT at 136) warrants immediate discontinuation to prevent progression to severe hepatotoxicity, which can include cholestatic jaundice or even acute liver failure.

Important Considerations

• Methimazole-induced liver injury typically presents within the first few weeks to months of treatment, consistent with this patient's timeline
• Although methimazole-induced liver injury is less common than with propylthiouracil, it can still cause significant hepatotoxicity requiring prompt intervention
• Cholestatic pattern of injury has been reported with methimazole 3, 4, 5, so monitoring for jaundice is essential
• Untreated hyperthyroidism itself can cause mild liver enzyme elevations, but not typically to this degree

Pitfalls to Avoid

1. Do not continue methimazole at the same dose - this could lead to progressive liver injury
2. Do not simply reduce the methimazole dose - even at lower doses, continued exposure can worsen hepatotoxicity
3. Do not delay treatment of hyperthyroidism - untreated severe hyperthyroidism carries significant risks
4. Do not automatically switch to propylthiouracil - while it may be an option in some cases, PTU also carries hepatotoxicity risk and requires careful consideration

The liver enzyme elevations should normalize within 5-12 weeks after discontinuation of methimazole based on case reports 4, 5, but close monitoring is essential to ensure resolution.