What is the management of fetal Graves' disease?

Management of Fetal Graves' Disease

Fetal Graves' disease should be treated with carefully titrated maternal antithyroid medication (preferably propylthiouracil in first trimester, then methimazole) with the goal of maintaining maternal FT4 or FTI in the high-normal range using the lowest possible dose to avoid fetal hypothyroidism while controlling hyperthyroidism. 1

Diagnosis and Risk Assessment

High-Risk Pregnancies

• Women with current Graves' disease
• Women with past history of Graves' disease (even post-thyroidectomy or radioactive iodine ablation) 2
• Women with elevated thyroid-stimulating hormone receptor antibodies (TRAbs)

Diagnostic Algorithm

1. Maternal TRAb measurement - critical for risk assessment

   • High risk if TRAb levels exceed 2-3 times upper limit of normal 3
   • TRAbs can cross placenta and cause fetal hyperthyroidism even in mothers who are euthyroid or hypothyroid post-treatment

2. Fetal monitoring starting at 20 weeks gestation 3

   • Serial ultrasound assessments for:
     • Fetal goiter
     • Fetal heart rate (tachycardia >160 bpm suggests hyperthyroidism)
     • Fetal growth
     • Amniotic fluid volume

3. Differential diagnosis of fetal goiter

   • Fetal hyperthyroidism (due to maternal TRAbs)
   • Fetal hypothyroidism (due to excessive maternal antithyroid medication)

Treatment Approach

Medication Management

1. First trimester:

   • Propylthiouracil (PTU) is preferred due to lower risk of embryopathy 4, 5
   • Lowest effective dose to minimize fetal exposure

2. Second and third trimesters:

   • Consider switching to methimazole due to lower risk of hepatotoxicity 4
   • Dose titration based on maternal thyroid function and fetal assessment

3. Dosing principles:

   • Aim for high-normal or slightly elevated maternal thyroid function 1, 6
   • Antithyroid drugs block fetal thyroid more effectively than maternal thyroid 7
   • Progressively reduce dosage as pregnancy advances (hyperthyroidism often improves in later pregnancy) 6

Monitoring Protocol

• Maternal FT4 or FTI every 2-4 weeks 1
• Fetal heart rate and growth monitoring
• Ultrasound assessment of fetal thyroid gland

Management of Specific Scenarios

1. Fetal hyperthyroidism detected:

   • Increase maternal antithyroid medication dose
   • Consider adding beta-blockers (e.g., propranolol) for maternal symptom control 1

2. Fetal hypothyroidism detected (goiter with normal heart rate):

   • Decrease maternal antithyroid medication dose
   • Antithyroid drugs cross placenta more readily than levothyroxine, so adding levothyroxine to mother has limited benefit for fetus 7

3. Severe fetal tachycardia or heart failure:

   • Urgent consultation with maternal-fetal medicine specialist
   • Intensified monitoring and treatment adjustment

Important Considerations and Pitfalls

Medication Cautions

• Avoid radioactive iodine (I-131) - absolutely contraindicated in pregnancy 1
• Avoid surgical thyroidectomy during pregnancy if possible
  • Does not immediately eliminate TRAbs
  • Can lead to isolated fetal hyperthyroidism if antithyroid drugs are withdrawn 7

Neonatal Implications

• Inform pediatrician about maternal Graves' disease before delivery 1
• Neonatal thyroid dysfunction may require treatment for 1-3 months until maternal antibodies clear 3
• Monitor neonate for:
  • Hyperthyroidism (tachycardia, irritability, poor weight gain)
  • Hypothyroidism (if mother received high-dose antithyroid drugs)

Medication Side Effects

• Monitor for agranulocytosis (sore throat, fever) - discontinue medication and obtain CBC if suspected 1, 4
• Monitor for hepatotoxicity, especially with PTU 5
• Bleeding risk may be increased, particularly with surgical procedures 5

By following this management approach, the risks of both maternal and fetal complications from Graves' disease can be minimized, optimizing outcomes for both mother and baby.