What is the recommended propylthiouracil (PTU) dosage and titration for a pregnant woman with active hyperthyroidism, especially in the first trimester?

PTU Dosage for Pregnancy

Use propylthiouracil exclusively during the first trimester at the lowest dose that maintains free T4 in the high-normal range, then switch to methimazole for the second and third trimesters to minimize both fetal congenital malformations and maternal hepatotoxicity. 1

First Trimester: PTU Dosing Strategy

Target & Titration:

• Aim to maintain free T4 (or free thyroxine index) in the high-normal range—not mid-normal or low-normal—using the minimum effective PTU dose 1, 2
• This strategy maintains mild maternal hyperthyroidism to avoid fetal thyroid suppression while controlling maternal disease 1
• Check free T4 or FTI every 2–4 weeks throughout the first trimester to guide dose adjustments 1, 2, 3

Practical Dosing Considerations:

• While specific starting doses are not detailed in the guidelines, the FDA label notes that severe hepatotoxicity has been reported primarily with PTU doses ≥300 mg/day, though cases occur even at 50 mg/day 4
• Use the absolute minimum dose required to achieve the high-normal free T4 target 1

Switching to Methimazole After First Trimester

Timing & Rationale:

• Switch from PTU to methimazole at the start of the second trimester to reduce maternal hepatotoxicity risk while avoiding the period of organogenesis when methimazole-associated birth defects occur 1, 4
• PTU carries higher risk of liver injury (OR 2.40) and elevated transaminases (OR 3.96) compared to methimazole 5
• Methimazole has higher odds of birth defects during first trimester exposure (OR 1.29), including choanal and esophageal atresia 5, 6, 7

Critical Safety Monitoring

Hematologic Toxicity:

• Watch for sore throat or fever, which signal possible agranulocytosis 1, 2, 3
• Obtain immediate complete blood count and discontinue PTU immediately if agranulocytosis is confirmed 1

Hepatotoxicity:

• Monitor for tiredness, nausea, anorexia, fever, pharyngitis, or malaise—these warrant immediate PTU discontinuation and liver function testing 4
• Severe liver injury including hepatic failure requiring transplantation or resulting in death has been reported with PTU 4

Other Toxicities:

• Remain vigilant for vasculitis and thrombocytopenia as additional thioamide-related adverse effects 1, 3

Adjunctive Symptom Management

Beta-Blockers:

• Use propranolol temporarily to control tremor, palpitations, and tachycardia until PTU lowers thyroid hormone levels 1, 2, 3
• Discontinue beta-blockers once biochemical control is achieved 1
• Note that hyperthyroid patients may have increased clearance of beta-blockers; dose reduction may be needed as euthyroidism is approached 4

Monitoring Schedule

During Active Titration:

• Free T4 or FTI every 2–4 weeks to adjust PTU dosage 1, 2, 3

Once Stable:

• Check TSH every trimester after achieving stable control 1, 2

Fetal & Neonatal Considerations

Monitoring:

• Monitor fetal heart rate and growth in women with Graves' disease 1
• Inform the newborn's physician about maternal thyroid disease due to risk of neonatal thyroid dysfunction 1, 2

Transient Effects:

• Transient fetal or neonatal thyroid suppression may occur with thioamide therapy but is usually self-limited and rarely requires treatment 1

Risks of Inadequate Treatment

Maternal Complications:

• Untreated or inadequately treated hyperthyroidism increases risk of severe preeclampsia, preterm delivery, heart failure, miscarriage, and thyroid storm 1, 2, 3

Fetal Complications:

• Low birth weight and potential thyroid dysfunction are associated with inadequate maternal treatment 1, 2, 3

Special Situations

Hyperemesis Gravidarum:

• Biochemical hyperthyroidism with hyperemesis gravidarum rarely requires treatment unless other clinical signs of hyperthyroidism are present 1, 2

Thyroid Storm:

• This is a medical emergency requiring immediate treatment without waiting for laboratory confirmation 1, 2
• Standard regimen includes PTU (or methimazole), potassium/sodium iodide solutions, dexamethasone, phenobarbital, and supportive care 1, 2
• Avoid delivery during thyroid storm unless absolutely necessary 1, 2

Surgical Intervention:

• Thyroidectomy is reserved only for women who fail thioamide therapy or develop severe drug intolerance (agranulocytosis, marked hepatotoxicity) 1, 2, 3
• If surgery is necessary, perform during the second trimester 1, 2

Absolute Contraindications

Radioactive Iodine:

• I-131 is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation 1, 2, 3
• Women must wait four months after I-131 treatment before breastfeeding 1, 2

Breastfeeding Guidance

• Both PTU and methimazole are compatible with breastfeeding, as only minimal amounts enter breast milk 1, 4

Common Pitfalls to Avoid

• Do not target mid-normal or low-normal free T4 levels—this increases risk of fetal hypothyroidism; always aim for high-normal range 1
• Do not continue PTU beyond first trimester without switching to methimazole—this increases maternal hepatotoxicity risk 1
• Do not delay treatment of overt hyperthyroidism—this poses significant risks to both mother and fetus 3
• Do not use radioactive iodine under any circumstances during pregnancy 2, 3