Treatment of Hyperthyroidism in Pregnancy
Propylthiouracil (PTU) is the preferred antithyroid medication during the first trimester of pregnancy, with consideration to switch to methimazole for the second and third trimesters to minimize maternal hepatotoxicity risk. 1, 2, 3
First-Line Pharmacologic Management
First Trimester Treatment
- Use propylthiouracil (PTU) exclusively during the first trimester because methimazole carries a small but definite risk of specific congenital malformations including choanal atresia, esophageal atresia, and omphalocele. 1, 4, 5
- PTU is safer than methimazole for fetal outcomes in early pregnancy, with meta-analysis confirming lower rates of congenital anomalies (OR 0.80,95% CI 0.69-0.92). 4
Second and Third Trimester Treatment
- Switch from PTU to methimazole after the first trimester to reduce maternal risk of severe hepatotoxicity, which occurs in approximately 0.1% of PTU-exposed adults and can progress to hepatic failure requiring transplantation or resulting in death. 1, 2, 6
- This trimester-specific approach balances fetal teratogenic risk against maternal hepatotoxic risk. 5, 7
Treatment Goals and Monitoring
Dosing Strategy
- Maintain Free T4 or Free T4 Index (FTI) in the high-normal range using the lowest possible thioamide dosage to minimize fetal thyroid suppression while adequately treating maternal disease. 8, 1
- Monitor Free T4 or FTI every 2-4 weeks to adjust medication dosage appropriately. 8, 1
- Once stable, check TSH levels every trimester. 1
Symptomatic Management
- Add beta-adrenergic blockers (e.g., propranolol) for symptomatic relief while awaiting thyroid hormone normalization, particularly for tachycardia, tremor, and anxiety. 8, 9
Critical Safety Monitoring
Maternal Monitoring for Drug Toxicity
- Monitor for agranulocytosis: If sore throat and fever develop, obtain complete blood count immediately and discontinue thioamide. 8, 9
- Monitor for hepatotoxicity with PTU: If tiredness, nausea, anorexia, fever, pharyngitis, or malaise occur, discontinue PTU immediately and obtain liver function tests. 2
- Monitor for vasculitis: Promptly evaluate new rash, hematuria, decreased urine output, dyspnea, or hemoptysis, as vasculitis can result in severe complications and death. 2
- Other serious adverse effects include thrombocytopenia and hepatitis. 8
Fetal and Neonatal Monitoring
- Monitor fetal thyroid size by ultrasound because thioamides cross the placenta and can cause fetal hypothyroidism with or without goiter in approximately 9.5% of exposed fetuses. 10
- Monitor fetal heart rate and growth in women with Graves' disease due to risk of fetal thyrotoxicosis from transplacental passage of thyroid-stimulating antibodies. 1
- Inform the newborn's physician about maternal Graves' disease because neonatal thyroid dysfunction (both hypo- and hyperthyroidism) can occur and requires monitoring. 1, 10
Risks of Untreated Hyperthyroidism
Inadequately treated maternal hyperthyroidism significantly increases risks of:
- Severe preeclampsia 8, 1
- Preterm delivery 8, 1
- Maternal heart failure 8, 1
- Miscarriage 8, 1
- Low birth weight 8, 1
Alternative and Emergency Treatments
Thyroid Storm Management
- Thyroid storm is a medical emergency requiring immediate treatment with propylthiouracil or methimazole, potassium/sodium iodide solutions, dexamethasone, and supportive care. 1
Surgical Management
- Reserve thyroidectomy for women who do not respond to thioamide therapy, have large goiters causing compressive symptoms, or have specific contraindications to medical therapy. 9, 1
- Surgery is preferably performed in the second trimester if needed. 1
Absolute Contraindications
- Radioactive iodine (I-131) is absolutely contraindicated during pregnancy due to fetal thyroid ablation risk. 1
- Women should not breastfeed for four months after I-131 treatment. 1
Breastfeeding Considerations
- Women treated with either propylthiouracil or methimazole can safely breastfeed because both drugs are present in breast milk only in clinically insignificant amounts. 8, 1, 2, 3
- Methimazole is preferred during lactation due to better maternal safety profile. 7