Anti-Thyroid Medication in the 2nd Trimester of Pregnancy
Switch from propylthiouracil (PTU) to methimazole (MMI) for the second trimester of pregnancy, as MMI is the preferred agent during this period while PTU is reserved for the first trimester due to its lower risk of congenital malformations during organogenesis. 1
Medication Selection by Trimester
Second Trimester Approach
- Methimazole is the preferred antithyroid medication for the second and third trimesters 1
- PTU carries a significant risk of severe hepatotoxicity that can progress to liver failure during pregnancy, making it less suitable for prolonged use 2
- The strategy of switching between thionamide drugs aims to minimize both the teratogenic risk of MMI in early pregnancy and the hepatotoxic risk of PTU with continued use 1, 3
Rationale for the Switch
- MMI is associated with congenital malformations (choanal atresia, esophageal atresia, aplasia cutis) primarily when exposure occurs during first-trimester organogenesis 3, 2, 4
- By the second trimester, organogenesis is complete, making MMI's teratogenic risk substantially lower 3
- PTU-induced hepatotoxicity can be catastrophic in pregnancy, with risk of maternal liver failure 2, 4
Treatment Goals and Monitoring
Target Thyroid Levels
- Maintain free T4 (FT4) or free thyroxine index (FTI) in the high-normal to upper one-third of the trimester-specific reference range using the lowest possible thioamide dose 5, 1, 4
- This approach ensures maternal euthyroidism while minimizing fetal thyroid suppression 5
Monitoring Schedule
- Check FT4 or FTI every 2-4 weeks to guide dosage adjustments 5, 1
- Monitor TSH every trimester once stable 5, 1
- A rising serum TSH indicates the need for a lower maintenance dose 3
Critical Safety Considerations
Fetal Thyroid Protection
- Antithyroid drugs cross the placenta and can suppress fetal thyroid function more effectively than maternal thyroid function 6
- By 20 weeks' gestation, the fetal thyroid is fully responsive to both maternal TSH-receptor antibodies and antithyroid drugs 7
- Fetal and neonatal thyroid suppression from thioamides is usually transient and rarely requires treatment 5
Monitoring for Drug Toxicity
- Agranulocytosis presents with sore throat and fever; obtain complete blood count immediately and discontinue the thioamide if suspected 5, 1
- Monitor for hepatitis, vasculitis, and thrombocytopenia 5
- Check prothrombin time before surgical procedures due to potential hypoprothrombinemia 3
Adjunctive Management
Symptom Control
- Beta-blockers (e.g., propranolol) can temporarily manage symptoms like tremors and palpitations until thioamide therapy reduces thyroid hormone levels 5, 1
- Note that beta-blocker dosing may need reduction as the patient becomes euthyroid due to decreased clearance 3
Risks of Inadequate Treatment
- Untreated or inadequately treated hyperthyroidism increases risks of preeclampsia, preterm delivery, heart failure, spontaneous abortion, and stillbirth 1, 3, 7
- Fetal risks include low birth weight and thyroid dysfunction 1
Special Situations
When Surgery May Be Necessary
- Thyroidectomy should be reserved for women who do not respond to thioamide therapy or develop severe drug intolerance (agranulocytosis, severe hepatotoxicity) 1
- If surgery is required, the second trimester is the optimal timing with lower risk than first or third trimester 1, 8
- Caution: Thyroidectomy during active Graves' disease does not immediately eliminate TSH-receptor antibodies and may lead to isolated fetal hyperthyroidism if antithyroid drugs are withdrawn 6
Absolute Contraindications
- Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation 5, 1, 8
- Women must wait 4 months after I-131 treatment before breastfeeding 5, 8