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

Management of Graves' Disease in Pregnancy

Treat all pregnant patients with Graves' disease using thioamide medications, with propylthiouracil (PTU) as first-line during the first trimester, then switch to methimazole for the second and third trimesters, maintaining free T4 in the high-normal range with the lowest possible dose. 1

Diagnostic Confirmation

• Confirm Graves' disease by measuring TSH (suppressed) and free T4 or free thyroxine index (elevated) in the absence of thyroid nodules 1
• Look for distinctive clinical features that differentiate Graves' disease from normal pregnancy: eyelid lag/retraction, pretibial myxedema, thyroid bruit, tremors, excessive sweating beyond typical pregnancy changes, and tachycardia disproportionate to gestational age 1
• Measure TSH receptor antibodies (TRAb) early in the third trimester—elevated levels (e.g., >200 IU/L) indicate risk for fetal and neonatal thyrotoxicosis and necessitate continued treatment throughout pregnancy 2, 3

Medication Selection Algorithm

First Trimester (Weeks 1-13)

• Use propylthiouracil (PTU) exclusively because methimazole carries risk of congenital malformations including aplasia cutis, choanal atresia, and esophageal atresia 1, 4, 5
• PTU is preferred despite its hepatotoxicity risk because teratogenic effects of methimazole during organogenesis are the greater concern 4

Second and Third Trimesters (Weeks 14-40)

• Switch from PTU to methimazole due to PTU's risk of severe maternal hepatotoxicity including hepatic failure 1, 4
• This switch is critical—PTU hepatotoxicity can be life-threatening and methimazole's teratogenic risk is confined to the first trimester 5

Dosing Strategy and Monitoring

• Target free T4 in the high-normal range or just above the upper limit of normal using the lowest possible thioamide dose 1, 3, 6
• This approach minimizes fetal thyroid suppression while preventing maternal complications (preeclampsia, preterm delivery, miscarriage, heart failure) 1, 7
• Monitor free T4 or free thyroxine index every 2-4 weeks initially, then adjust based on stability 2, 7
• Reduce dosage progressively as pregnancy advances—hyperthyroidism typically ameliorates in later pregnancy, and approximately one-third of patients can discontinue medication in the second half of pregnancy 6

Critical Monitoring for Complications

• Assess at each visit for signs of inadequate control: persistent tachycardia, excessive weight loss, hypertension 1
• Monitor for medication side effects: agranulocytosis (sore throat, fever), hepatitis (anorexia, pruritus, right upper quadrant pain), vasculitis (new rash, hematuria, decreased urine output, dyspnea, hemoptysis) 4, 5
• Obtain white blood cell count and differential if any signs of illness develop 4, 5
• Consider beta-blockers (propranolol or atenolol) for symptomatic relief of palpitations and tachycardia while awaiting thioamide effect 2

Fetal Considerations

• Elevated maternal TRAb levels require continued antithyroid treatment throughout pregnancy regardless of maternal thyroid status, as these antibodies cross the placenta and can cause fetal thyrotoxicosis 2, 3
• Evaluate fetal thyroid by ultrasound if TRAb levels are elevated in the third trimester, looking for goiter, tachycardia, or growth restriction 3, 8
• Inform the newborn's physician about maternal Graves' disease—measure cord blood TSH and free T4 at delivery in all cases 2, 3
• Neonatal thyrotoxicosis can develop in the first few days after birth as maternal antithyroid drug clears, lasting several months until maternal antibodies clear 3

Common Pitfalls to Avoid

• Never use radioactive iodine (I-131) in pregnancy—it is absolutely contraindicated 1
• Avoid over-treatment with antithyroid drugs, as they block fetal thyroid function more effectively than maternal thyroid function, and maternal levothyroxine replacement does not adequately reach the fetus 8
• Do not perform thyroidectomy during pregnancy except in rare cases of medication intolerance or non-response—surgery does not immediately resolve the autoimmune process and withdrawal of antithyroid medication post-operatively creates high risk for isolated fetal hyperthyroidism 1, 8
• Limit PTU prescriptions to only the amount needed until the next visit, as patients may continue medication unsupervised 6

Thyroid Storm Management

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

Postpartum Management

• Evaluate thyroid function 6 weeks postpartum—hyperthyroidism frequently recurs as Graves' disease or postpartum thyroiditis 1, 7
• Women can safely breastfeed while taking PTU or methimazole, as both are present in breast milk in clinically insignificant amounts 1, 5
• Monitor thyroid function in breastfeeding mothers at frequent (weekly or biweekly) intervals 5

Preconception Counseling

• Ideally, treat Graves' disease definitively with radioiodine or surgery before pregnancy to avoid the complexities of managing hyperthyroidism during gestation 6
• For women who have had prior thyroid ablation or thyroidectomy, measure TRAb during pregnancy as these antibodies can persist and affect the fetus even after definitive maternal treatment 9