II. Indications
- Hyperthyroidism in children and adolescents
- Pregnancy (PTU)
- Severe Grave's Disease (e.g. Thyroid Storm)
- Subclinical Hyperthyroidism
III. Mechanism
- Thionamides block T3 and T4 synthesis (by inhibiting Thyroid peroxidase)
IV. Dose: Grave's Disease
- Target dose to Free T4 high end of normal range
- Methimazole (Tapazole)
- Preferred first-line agent
- Avoid in first trimester due to congenital defect risk
- Esophageal atresia
- Choanal Atresia
- Aplasia cutis
- Abdominal wall defects
- Ventricular Septal Defect
- Advantages over Propylthiouracil (PTU)
- Once daily dosing
- Decreases T4 and T3 levels more rapidly
- Much safer than PTU
- Lower risk of Agranulocytosis at moderate doses
- Does not carry the same liver toxicity risk as PTU
- Dosing: Hyperthyroidism
- Start: 10-30 mg PO qd
- Titrate Methimazole dose down after 4-6 weeks
- Goal: maintain normal Thyroid function
- Dose: reduce to 5-10 mg per day
- Dosing: Other
- Subclinical Hyperthyroidism: 5 mg PO qd
- Propylthiouracil (PTU)
- Indications (reasons to use PTU instead of Methimazole)
- Lactation
- Pregnancy (both PTU and Methimazole are Category D)
- Use PTU in first trimester
- Use Methimazole in second and third trimester
- Dosing: Hyperthyroidism
- Start: 100 mg po tid
- Maximum: 150 mg every 6-8 hours
- Titrate PTU dose down after 4-6 weeks
- Goal: maintain normal Thyroid function
- Dose: reduce to 50-100 mg per day
- Dosing: Other
- Thyroid Storm: 1 gram load, then 300 mg PO q6 hours
- Subclinical Hyperthyroidism: 50-100 mg PO qd
- Indications (reasons to use PTU instead of Methimazole)
V. Adverse effects (3 per 1000 patients)
-
Drug-Induced Agranulocytosis (more common with PTU)
- Risk increases over age 40 years
- Occurs in 0.17% of those on Methimazole
- Presentation: Infection (e.g. Pharyngitis)
- Course
- Resolves within 2-3 weeks after drug stopped
- Severe, refractory course may occur
- Contraindication to further Antithyroid Drugs
-
Jaundice
- Cholestatic Jaundice
- Occurs more commonly with Methimazole
- Hepatitis
- Occurs with both Methimazole and Propylthiouracil (PTU)
- Methimazole associated hepatitis
- Incidence: 3.17 per 1000 person-years
- Acute Hepatic Failure: 0.32 per 1000 person-years
- Propylthiouracil (PTU) is associated with severe liver injury
- Adults: 1 in 10,000
- Children: 1 in 2,000
- Vasculitis
- Lupus-Like Syndrome
- Aplastic Anemia
- Rash or Pruritus
- Switch from PTU to Methimazole if severe
- Arthralgia or Polyarthritis
- Fever
- Congenital abnormalities possible with Methimazole
VI. Monitoring
- Repeat examination every 3 months
- Pregnancy Test before starting therapy
- Lab Testing while on antithyroid medications: Monthly for 6 to 12 months
- Complete Blood Count (CBC)
- Obtain at baseline
- Repeat if Pharyngitis or fever occur (need not be done without symptoms or signs)
- Liver Function Tests
- Obtain at baseline and if symptoms develop
- Thyroid Function Tests (baseline, then every 4-8 weeks, then after stabilizing, every 3 months)
- Thyroid Stimulating Hormone (TSH) after stabilizing, once on every 3 month schedule
- Free T4
- Free T3
- Complete Blood Count (CBC)
- Lab Testing after completing antithyroid medications
- Obtain Thyroid Function Tests every 1-3 months for 6-12 months
- Indications to discontinue medication (via taper)
- Total treatment course of 12-18 months AND
- TSH normalized for 6-12 months
- Indications to consider Thyroid ablation
- Inadequate suppression at 12 months from initiation
VII. Efficacy: Predictors of Relapse (occurs in 30-70% of cases within first year)
- Tobacco Abuse
- Large Goiter
- Thyroid Stmulating Antibody high at end of treatment
VIII. References
Images: Related links to external sites (from Bing)
Related Studies
propylthiouracil (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
PROPYLTHIOURACIL 50 MG TABLET | Generic | $0.42 each |
methimazole (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
METHIMAZOLE 10 MG TABLET | Generic | $0.11 each |
METHIMAZOLE 5 MG TABLET | Generic | $0.06 each |