Antithyroid Drug

Aka: Antithyroid Drug, Thioamide, Propylthiouracil, PTU, Methimazole, Tapazole

1. See Also
   1. Hyperthyroidism
   2. Hyperthyroidism Management
2. Indications
   1. Hyperthyroidism in children and adolescents
   2. Pregnancy (PTU)
   3. Severe Grave's Disease (e.g. Thyroid Storm)
   4. Subclinical Hyperthyroidism
3. Dose: Grave's Disease
   1. Target dose to Free T4 high end of normal range
   2. Methimazole (Tapazole)
      1. Preferred first-line agent
      2. Advantages over Propylthiouracil (PTU)
         1. Once daily dosing
         2. Decreases T4 and T3 levels more rapidly
         3. Much safer than PTU
            1. Lower risk of Agranulocytosis at moderate doses
            2. Does not carry the same liver toxicity risk as PTU
      3. Dosing: Hyperthyroidism
         1. Start: 10-30 mg PO qd
         2. Titrate Methimazole dose down after 4-6 weeks
            1. Goal: maintain normal Thyroid function
            2. Dose: reduce to 5-10 mg per day
      4. Dosing: Other
         1. Subclinical Hyperthyroidism: 5 mg PO qd
   3. Propylthiouracil (PTU)
      1. Indications (reasons to use PTU instead of Methimazole)
         1. Lactation
         2. Pregnancy (both PTU and Methimazole are Category D)
            1. Use PTU in first trimester
            2. Use Methimazole in second and third trimester
      2. Dosing: Hyperthyroidism
         1. Start: 100 mg po tid
         2. Maximum: 150 mg every 6-8 hours
         3. Titrate PTU dose down after 4-6 weeks
            1. Goal: maintain normal Thyroid function
            2. Dose: reduce to 50-100 mg per day
      3. Dosing: Other
         1. Thyroid Storm: 1 gram load, then 300 mg PO q6 hours
         2. Subclinical Hyperthyroidism: 50-100 mg PO qd
4. Adverse effects (3 per 1000 patients)
   1. Drug-Induced Agranulocytosis (more common with PTU)
      1. Risk: over age 40 years
      2. Presentation: Infection (e.g. Pharyngitis)
      3. Course
         1. Resolves within 2-3 weeks after drug stopped
         2. Severe, refractory course may occur
      4. Contraindication to further Antithyroid Drugs
   2. Jaundice
      1. Cholestatic Jaundice
      2. Occurs more commonly with Methimazole
   3. Hepatitis
      1. Occurs with both Methimazole and Propylthiouracil (PTU)
      2. Propylthiouracil (PTU) is associated with severe liver injury
         1. Adults: 1 in 10,000
         2. Children: 1 in 2,000
   4. Vasculitis
   5. Lupus-like syndrome
   6. Aplastic Anemia
   7. Rash or Pruritus
      1. Switch from PTU to Methimazole if severe
   8. Arthralgia or Polyarthritis
   9. Fever
   10. Congenital abnormalities possible with Methimazole
5. Monitoring
   1. Repeat examination every 3 months
   2. Pregnancy Test before starting therapy
   3. Lab Testing monthly for 6 to 12 months
      1. Complete Blood Count (CBC)
      2. Liver Function Tests
      3. Thyroid Stimulating Hormone (TSH)
      4. Free T4
      5. Free T3
   4. Indications to discontinue medication
      1. TSH normalized for 6-12 months
   5. Indications to consider Thyroid ablation
      1. Inadequate suppression at 12 months from initiation
6. Efficacy: Predictors of Relapse (occurs in 50% of cases)
   1. Tobacco abuse
   2. Large Goiter
   3. Thyroid Stmulating Antibody high at end of treatment