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Antithyroid Drug

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Antithyroid Drug, Thioamide, Thionamide, Propylthiouracil, PTU, Methimazole, Tapazole

  • Indications
  1. Hyperthyroidism in children and adolescents
  2. Pregnancy (PTU)
  3. Severe Grave's Disease (e.g. Thyroid Storm)
  4. Subclinical Hyperthyroidism
  • Mechanism
  1. Thionamides block T3 and T4 synthesis (by inhibiting Thyroid peroxidase)
  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
  • Adverse effects (3 per 1000 patients)
  1. Drug-Induced Agranulocytosis (more common with PTU)
    1. Risk increases over age 40 years
    2. Occurs in 0.17% of those on Methimazole
    3. Presentation: Infection (e.g. Pharyngitis)
    4. Course
      1. Resolves within 2-3 weeks after drug stopped
      2. Severe, refractory course may occur
    5. 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. Methimazole associated hepatitis
      1. Incidence: 3.17 per 1000 person-years
      2. Acute Hepatic Failure: 0.32 per 1000 person-years
    3. 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
  • Monitoring
  1. Repeat examination every 3 months
  2. Pregnancy Test before starting therapy
  3. Lab Testing while on antithyroid medications: Monthly for 6 to 12 months
    1. Complete Blood Count (CBC)
      1. Obtain at baseline
      2. Repeat if Pharyngitis or fever occur (need not be done without symptoms or signs)
    2. Liver Function Tests
      1. Obtain at baseline and if symptoms develop
    3. Thyroid Function Tests (baseline, then every 4-8 weeks, then after stabilizing, every 3 months)
      1. Thyroid Stimulating Hormone (TSH) after stabilizing, once on every 3 month schedule
      2. Free T4
      3. Free T3
  4. Lab Testing after completing antithyroid medications
    1. Obtain Thyroid Function Tests every 1-3 months for 6-12 months
  5. Indications to discontinue medication (via taper)
    1. Total treatment course of 12-18 months AND
    2. TSH normalized for 6-12 months
  6. Indications to consider Thyroid ablation
    1. Inadequate suppression at 12 months from initiation
  • Efficacy
  • Predictors of Relapse (occurs in 30-70% of cases within first year)
  1. Tobacco Abuse
  2. Large Goiter
  3. Thyroid Stmulating Antibody high at end of treatment