What is the recommended treatment for hyperthyroidism (excessive thyroid hormone production) in pregnancy?

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 hypoprothrombinemia requiring prothrombin time monitoring, especially before surgical procedures. 8, 2, 3

Fetal and Neonatal Monitoring

• Monitor for fetal thyroid dysfunction: Hypothyroidism occurs in approximately 9.5% of fetuses exposed to PTU, with 56.8% developing goiter. 10
• Women with Graves' disease require monitoring for normal fetal heart rate and appropriate growth due to 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 due to transplacental antibody passage. 8, 1

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
• Thyroid storm (a medical emergency requiring intensive treatment with thioamides, potassium/sodium iodide solutions, dexamethasone, and supportive care) 1

Alternative and Contraindicated Treatments

Surgical Management

• Reserve thyroidectomy for women who do not respond to thioamide therapy, have large goiters causing compressive symptoms, or cannot tolerate medical therapy. 9, 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

• Both PTU and methimazole are compatible with breastfeeding, as only clinically insignificant amounts are excreted in breast milk (PTU: 0.025% of maternal dose excreted over 4 hours). 8, 1, 2
• Methimazole is preferred during lactation due to better maternal safety profile. 7

Special Clinical Scenarios

Biochemical Hyperthyroidism with Hyperemesis Gravidarum

• This condition rarely requires antithyroid treatment unless other clinical signs of hyperthyroidism are present, as it typically resolves spontaneously. 1

Preconception Planning

• Women with hyperthyroidism should ideally achieve euthyroidism before pregnancy, as thyroid dysfunction often diminishes as pregnancy progresses, allowing dosage reduction or discontinuation in some cases. 1