What is the recommended management for hyperthyroidism in pregnancy?

Management of Hyperthyroidism in Pregnancy

Use propylthiouracil (PTU) as first-line treatment during the first trimester, then switch to methimazole for the second and third trimesters to minimize both congenital malformations and maternal hepatotoxicity. 1, 2

Medication Selection by Trimester

First Trimester (Weeks 1-13)

• PTU is the preferred agent because methimazole carries a higher risk of congenital malformations, including choanal atresia and a specific embryopathy pattern. 1, 2, 3
• The FDA label confirms that methimazole-associated congenital malformations make PTU preferable during organogenesis. 4
• Start PTU and maintain throughout the first trimester even though PTU carries rare but severe hepatotoxicity risk, as the teratogenic risk of methimazole during organogenesis outweighs this concern. 5, 6

Second and Third Trimesters (Weeks 14-40)

• Switch from PTU to methimazole after the first trimester is complete to reduce the risk of maternal liver failure. 1, 2, 5
• PTU-induced hepatotoxicity can be catastrophic during pregnancy, with risk of liver failure threatening maternal and fetal survival. 6
• The FDA labels for both drugs support this trimester-based switching strategy. 4, 5

Treatment Goals and Monitoring

Target Thyroid Levels

• Maintain free T4 or free thyroxine index (FTI) in the high-normal range using the lowest effective thioamide dose. 1, 2
• Keep TSH in the lower-normal range to avoid overtreatment. 7
• This approach minimizes fetal hypothyroidism risk while controlling maternal hyperthyroidism. 8

Monitoring Schedule

• Check free T4 or FTI every 2-4 weeks to adjust medication dosage. 1, 2
• Monitor TSH every trimester once stable thyroid function is achieved. 1, 2
• Check prothrombin time before surgical procedures due to potential vitamin K inhibition by thioamides. 4, 5

Symptom Management

Beta-Blocker Use

• Propranolol can be used temporarily to control tremors and palpitations until thioamide therapy reduces thyroid hormone levels. 1
• Reduce beta-blocker dose when the patient becomes euthyroid due to decreased clearance. 4, 5

Surgical Intervention

Indications for Thyroidectomy

• Reserve surgery for women who do not respond to thioamide therapy or develop severe drug intolerance (agranulocytosis, severe hepatotoxicity). 1, 2
• The second trimester is the optimal timing if surgery becomes necessary. 1

Absolute Contraindication

• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation. 1, 2
• Women must wait four months after I-131 treatment before attempting pregnancy or breastfeeding. 1

Special Clinical Scenarios

Hyperemesis Gravidarum

• Biochemical hyperthyroidism associated with hyperemesis gravidarum rarely requires treatment unless other clinical signs of hyperthyroidism are present. 1, 2
• Avoid routine thyroid testing in hyperemesis unless hyperthyroid signs exist. 1

Thyroid Storm

• This is a medical emergency presenting with fever, disproportionate tachycardia, altered mental status, vomiting, diarrhea, and cardiac arrhythmia. 1, 2
• Begin treatment immediately without waiting for laboratory confirmation. 1
• Treatment includes PTU or methimazole, potassium/sodium iodide solutions, dexamethasone, phenobarbital, and supportive care. 1, 2
• Avoid delivery during thyroid storm unless absolutely necessary. 1

Monitoring for Drug Toxicity

Warning Signs Requiring Immediate Drug Discontinuation

• Agranulocytosis: sore throat and fever. 1
• Hepatotoxicity: tiredness, nausea, anorexia, fever, pharyngitis, or malaise. 5
• Vasculitis: new rash, hematuria, decreased urine output, dyspnea, or hemoptysis. 5
• Obtain white blood cell count, liver function tests, and transaminase levels immediately if these symptoms develop. 5

Fetal and Neonatal Considerations

Risks of Untreated Hyperthyroidism

• Inadequately treated hyperthyroidism increases risks of preeclampsia, preterm delivery, heart failure, miscarriage, low birth weight, and stillbirth. 1, 2, 5
• These maternal and fetal risks far outweigh the rare adverse effects of antithyroid drugs. 9

Neonatal Monitoring

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

Dose Adjustments During Pregnancy

Natural Disease Course

• Thyroid dysfunction often diminishes as pregnancy progresses, allowing dosage reduction or even discontinuation several weeks to months before delivery in some cases. 2, 4, 5
• A rising TSH indicates the need for a lower maintenance dose. 4, 5

Breastfeeding Considerations

• Women treated with either PTU or methimazole can safely breastfeed, as both drugs are present in breast milk in clinically insignificant amounts. 2, 4, 5