What is the treatment for a pregnant patient with Graves' disease?

Treatment of Graves' Disease in Pregnancy

Treat Graves' disease in pregnancy with thioamide medications, using propylthiouracil (PTU) during the first trimester and switching to methimazole for the second and third trimesters, while maintaining maternal free T4 in the high-normal range with the lowest effective dose. 1, 2, 3

First Trimester: Propylthiouracil (PTU)

• PTU is the preferred agent during the first trimester because methimazole carries a risk of congenital malformations including aplasia cutis, choanal atresia, and esophageal atresia. 1, 3
• Start PTU and monitor free T4 or free thyroxine index (FTI) every 2-4 weeks initially. 4, 1
• The goal is to maintain maternal free T4 at the upper limit of normal or slightly elevated to minimize fetal thyroid suppression while preventing maternal complications. 1, 5, 6

Second and Third Trimesters: Switch to Methimazole

• Switch from PTU to methimazole after the first trimester due to PTU's risk of severe maternal hepatotoxicity, including hepatic failure. 1, 2, 3
• Methimazole is preferred for pediatric patients and has a better safety profile for maternal liver function compared to PTU. 3
• Continue targeting free T4 in the high-normal range using the lowest possible dose. 1, 6

Monitoring Strategy

• Check thyroid function (TSH and free T4) every 2-4 weeks during dose adjustments, then every trimester once stable. 4, 1
• Monitor for signs of inadequate control at each visit: persistent tachycardia (>100 bpm at rest), excessive weight loss, hypertension, and tremors. 1
• Measure thyrotropin receptor antibodies (TRAb) early in the third trimester if not already done, as elevated levels (>3 times upper limit of normal) predict fetal and neonatal thyrotoxicosis. 4, 7, 6
• If TRAb levels are significantly elevated (e.g., >200 IU/L), continue treatment throughout pregnancy regardless of maternal euthyroid status to prevent fetal thyrotoxicosis. 4

Symptomatic Management

• Propranolol can be used temporarily to control symptoms like palpitations and tachycardia until thioamide therapy reduces thyroid hormone levels. 4
• Beta-blockers should be used cautiously and for short duration, as prolonged use may affect fetal growth. 4

Critical Safety Monitoring

For PTU (First Trimester):

• Warn patients to immediately report symptoms of hepatotoxicity: anorexia, pruritus, right upper quadrant pain, jaundice, dark urine, or pale stools. 2
• Monitor for agranulocytosis: instruct patients to report sore throat, fever, skin eruptions, or general malaise immediately. 2
• Obtain white blood cell count with differential if any signs of infection develop. 2

For Methimazole (Second/Third Trimesters):

• Monitor for agranulocytosis and vasculitis: patients should report sore throat, fever, new rash, hematuria, decreased urine output, or hemoptysis. 3
• Check prothrombin time before surgical procedures as both drugs may cause hypoprothrombinemia. 2, 3

Dose Adjustment Principles

• Reduce dosage progressively as pregnancy advances, since thyroid dysfunction typically ameliorates in later stages of pregnancy. 5
• In approximately one-third of patients, antithyroid medication can be discontinued in the second half of pregnancy. 5
• A rising serum TSH indicates the need for a lower maintenance dose. 2, 3

Thyroid Storm Management

• Recognize thyroid storm as a medical emergency: fever, tachycardia disproportionate to fever, altered mental status, vomiting, diarrhea, and cardiac arrhythmia. 1
• Treat immediately without waiting for confirmatory labs using PTU or methimazole, saturated solution of potassium iodide or sodium iodide, dexamethasone, and phenobarbital. 1

Surgical Considerations

• Reserve thyroidectomy for women who cannot tolerate thioamide medications or have severe adverse reactions. 1
• If surgery is necessary, perform during the second trimester to minimize risks of spontaneous abortion (first trimester) and preterm labor (third trimester). 1
• Radioactive iodine (I-131) is absolutely contraindicated in pregnancy. 1

Fetal and Neonatal Considerations

• Inform the newborn's physician about maternal Graves' disease due to risk of neonatal immune-mediated hyperthyroidism or hypothyroidism from transplacental antibody passage. 4
• Fetal thyroid suppression from maternal thioamide therapy is usually transient and rarely requires treatment. 4
• If maternal TRAb levels are elevated, consider fetal ultrasound monitoring for goiter and fetal heart rate assessment. 6
• Measure cord blood TSH and free T4 at delivery in women with active Graves' disease or history of thyroid ablation with positive TRAb. 6

Postpartum Management

• Evaluate thyroid function 6 weeks postpartum as hyperthyroidism may recur as Graves' disease or postpartum thyroiditis. 1, 7
• Breastfeeding is safe while taking PTU or methimazole, as both are present in breast milk in clinically insignificant amounts. 1, 2, 3
• Use the lowest effective dose during lactation and monitor infant thyroid function at frequent (weekly or biweekly) intervals initially. 3

Common Pitfalls to Avoid

• Do not over-treat: excessive thioamide dosing can cause fetal hypothyroidism and goiter. Target high-normal maternal free T4, not complete normalization. 1, 5, 6
• Do not continue PTU beyond first trimester due to maternal hepatotoxicity risk. 1, 2
• Do not use methimazole in first trimester if avoidable due to teratogenic risk. 1, 3
• Do not prescribe large quantities of medication without scheduled follow-up, as patients may continue treatment unsupervised. 5
• Do not ignore elevated TRAb levels: these require continued treatment and neonatal monitoring even if mother is euthyroid. 4