What is the appropriate propylthiouracil dosing regimen for a 6‑week pregnant woman with confirmed hyperthyroidism?

Propylthiouracil Dosing for Hyperthyroidism at 6 Weeks Gestation

Start propylthiouracil at 300 mg daily, divided into three equal doses given every 8 hours (100 mg three times daily), and plan to switch to methimazole after the first trimester is complete. 1, 2

Initial Dosing Strategy

• Standard starting dose is 300 mg daily in three divided doses (100 mg every 8 hours) for most pregnant women with hyperthyroidism 2
• For severe hyperthyroidism or very large goiters, the initial dose may be increased to 400 mg daily; rarely, 600–900 mg daily may be required initially 2
• At 6 weeks gestation, you are in the critical first trimester window when PTU is strongly preferred over methimazole due to lower teratogenic risk 3, 1

Rationale for PTU in First Trimester

• PTU is the preferred antithyroid medication during the first trimester because methimazole causes a specific pattern of congenital malformations including choanal atresia, aplasia cutis congenita, and facial/cardiac/gastrointestinal anomalies 3, 1, 4
• The American College of Obstetricians and Gynecologists recommends using PTU exclusively during the first trimester, then switching to methimazole for the second and third trimesters to minimize both congenital malformations and maternal hepatotoxicity 1
• While PTU carries a small risk of severe hepatotoxicity (including liver failure requiring transplantation), this risk is outweighed by methimazole's teratogenic effects during organogenesis 1, 4, 5

Treatment Goals and Monitoring

• Target free T4 or free thyroxine index (FTI) in the high-normal range using the lowest effective PTU dose—the goal is mild maternal hyperthyroidism rather than full euthyroidism to avoid fetal thyroid suppression 6, 3, 1
• Check free T4 or FTI every 2–4 weeks to guide dose adjustments 6, 3, 1
• Once stable thyroid function is achieved, check TSH every trimester 1

Medication Transition Plan

• Switch from PTU to methimazole after completing the first trimester (around 12–13 weeks gestation) to reduce the risk of maternal hepatotoxicity while avoiding the teratogenic window for methimazole 1, 4, 5
• Failing to make this switch increases the risk of PTU-related liver injury, which can be severe 1

Maintenance Dosing

• The usual maintenance dose of PTU is 100–150 mg daily once thyroid control is achieved 2
• Continue to use the minimum effective dose throughout treatment to limit drug exposure 1

Critical Safety Monitoring

Agranulocytosis

• Monitor for sore throat and fever, which signal potential agranulocytosis 6, 3, 1
• If these symptoms develop, obtain an immediate complete blood count and discontinue PTU 6, 1

Hepatotoxicity

• Although most severe liver injury cases occurred with PTU doses ≥300 mg/day, cases have been reported with doses as low as 50 mg/day 2
• Remain vigilant for signs of hepatitis, and consider switching to methimazole after the first trimester to mitigate this risk 6, 1

Other Adverse Effects

• Watch for vasculitis and thrombocytopenia as additional thioamide-related toxicities 6, 1

Adjunctive Symptom Management

• Use a beta-blocker such as propranolol temporarily to control tremors, palpitations, and tachycardia until PTU reduces thyroid hormone levels 6, 3, 1
• Discontinue the beta-blocker once biochemical control is achieved 1

Risks of Inadequate Treatment

• Untreated or inadequately controlled hyperthyroidism increases the risk of severe preeclampsia, preterm delivery, heart failure, miscarriage, and low birth weight 3, 1
• These maternal and fetal complications far outweigh the rare risks of antithyroid drug therapy 5

Fetal and Neonatal Considerations

• Transient fetal or neonatal thyroid suppression may occur with thioamide therapy but is usually self-limited and rarely requires treatment 6, 1
• Inform the newborn's physician about maternal Graves' disease to ensure appropriate neonatal thyroid monitoring 6, 3, 1

When Surgery Is Indicated

• Reserve thyroidectomy only for women who fail to respond to thioamide therapy or develop severe drug intolerance (agranulocytosis, marked hepatotoxicity) 6, 3, 1
• If surgery is necessary, perform it during the second trimester to minimize fetal risk 3, 1

Absolute Contraindications

• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy because it causes fetal thyroid ablation 6, 3, 1
• Women must wait at least 4 months after I-131 treatment before breastfeeding 3, 1

Common Pitfalls to Avoid

• Do not continue PTU throughout the entire pregnancy—switch to methimazole after the first trimester to reduce hepatotoxicity risk 1
• Do not aim for mid-normal or low-normal free T4 levels—this can cause fetal hypothyroidism; instead, target the high-normal range 6, 1
• Do not delay treatment while awaiting confirmatory testing—untreated hyperthyroidism poses greater risks than antithyroid drug therapy 5

Breastfeeding Guidance

• Both PTU and methimazole are compatible with breastfeeding, as only small amounts enter breast milk 6, 1