What is the management of hyperthyroidism in the 1st trimester of pregnancy?

Management of Hyperthyroidism in the First Trimester

Propylthiouracil (PTU) is the preferred antithyroid drug during the first trimester of pregnancy due to methimazole's association with rare but serious congenital malformations, despite PTU's risk of severe hepatotoxicity. 1, 2, 3

Pharmacologic Treatment Selection

First Trimester: PTU Preferred

• Use PTU as the first-line agent throughout the first trimester because methimazole has been associated with rare fetal abnormalities including choanal atresia and esophageal atresia, whereas PTU crosses the placenta minimally (only 0.025%) 1, 2, 4
• The FDA specifically states that PTU may be the treatment of choice when an antithyroid drug is indicated during or just prior to the first trimester, despite its black box warning for severe liver injury 3
• PTU should be reserved for patients who cannot tolerate methimazole and in whom radioactive iodine or surgery are not appropriate, except during the first trimester when it becomes preferred 3

Critical Caveat About PTU

• PTU carries a black box warning for severe liver injury and acute liver failure, some cases fatal, requiring liver transplantation in both adult and pediatric patients 3
• Counsel patients to immediately report tiredness, nausea, anorexia, fever, pharyngitis, or malaise, as these may indicate hepatotoxicity 3

Transition Strategy After First Trimester

• Switch from PTU to methimazole after the first trimester (beginning in the second trimester) to minimize maternal hepatotoxicity risk while avoiding the teratogenic window 3, 5, 4
• Methimazole up to 30 mg/day is considered safe in later pregnancy 2

Treatment Goals and Monitoring

Target Thyroid Levels

• Maintain maternal free T4 (FT4) or free thyroxine index (FTI) in the high-normal range or just above normal using the lowest effective thioamide dose 2
• This approach balances preventing maternal thyrotoxicosis complications while minimizing fetal hypothyroidism risk 2

Monitoring Frequency

• Check FT4 or FTI every 2-4 weeks during active treatment until stable 2
• Once TSH level is stable, continue monitoring every 4 weeks 2
• A rising serum TSH indicates the need for dose reduction 6, 5

Important Monitoring Pitfall

• Research shows that even low doses of PTU (≤100 mg daily) or MMI (≤10 mg daily) can cause fetal hypothyroidism in 14-21% of cases, while higher individualized doses may actually prevent fetal hypothyroidism 7
• Do not uniformly use the lowest possible dose; instead, titrate to maintain maternal FT4 in the high-normal range to avoid fetal hypothyroidism 7

Critical Safety Monitoring

Immediate Reporting Requirements

• Instruct patients to immediately report sore throat, fever, or signs of infection (agranulocytosis warning) 2, 3
• Obtain complete blood count immediately and discontinue thioamide if agranulocytosis is suspected 6
• Patients must promptly report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis, as these may indicate vasculitis 2, 3

Other Serious Adverse Effects

• Monitor for hepatitis, vasculitis, and thrombocytopenia 6, 2
• Consider monitoring prothrombin time, especially before surgical procedures, as thioamides may cause hypoprothrombinemia 3, 5

Symptomatic Management

• Use propranolol for symptomatic relief of tachycardia, tremor, and anxiety while awaiting thyroid hormone normalization 6
• Note that hyperthyroidism may cause increased clearance of beta blockers, and dose reduction may be needed when the patient becomes euthyroid 3, 5

Alternative Treatments

Radioactive Iodine

• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy 2, 5

Surgical Thyroidectomy

• Reserve thyroidectomy for patients who fail medical therapy, have large compressive goiters, or strongly prefer surgery 2
• If surgery is necessary, perform during the second trimester when safest 2

Risks of Untreated Hyperthyroidism

• Untreated or inadequately treated maternal hyperthyroidism significantly increases risks of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal or neonatal hyperthyroidism 3, 5, 8
• Outcomes correlate directly with disease control, making treatment essential despite medication risks 1

Fetal Considerations

• Both PTU and methimazole cross placental membranes and can induce fetal goiter and cretinism if excessive doses are used 3, 5
• Maternal thyroid-stimulating antibodies (in Graves' disease) can cross the placenta and cause fetal/neonatal thyroid dysfunction 6, 8
• Inform the pediatrician of maternal Graves' disease due to risk of neonatal thyroid dysfunction from transplacental antibody transfer 6