Management of Grave's Disease in Pregnancy
Treat Grave's disease in pregnancy with thioamide medications (propylthiouracil in 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 to prevent severe maternal complications including preeclampsia, heart failure, preterm delivery, and fetal thyrotoxicosis. 1, 2, 3
Diagnosis and Initial Assessment
Confirm the diagnosis by measuring TSH and free T4 (FT4) or free thyroxine index (FTI) - Grave's disease presents with elevated FT4 and suppressed TSH in the absence of thyroid nodules 1. Look specifically for:
- Distinctive clinical features: eyelid lag/retraction, pretibial myxedema, thyroid bruit 1
- Symptoms distinguishing pathologic hyperthyroidism from normal pregnancy: tremors, excessive sweating beyond typical pregnancy changes, tachycardia out of proportion to gestational age 1
Measure TSH-receptor antibodies (TRAb) in all pregnant women with Grave's disease to predict risk of fetal/neonatal thyroid dysfunction 4, 5. Elevated TRAb in the third trimester necessitates fetal thyroid ultrasound monitoring even in women with previously ablated disease 4.
Medical Management Strategy
First Trimester Treatment
Use propylthiouracil (PTU) as the preferred agent during the first trimester because methimazole carries risk of congenital malformations including aplasia cutis 2, 3, 6. However, both drugs have similar rates of fetal anomalies, and exposure to both drugs sequentially increases malformation risk compared to either alone 1, 5.
Second and Third Trimester Treatment
Switch from PTU to methimazole after the first trimester due to PTU's risk of severe maternal hepatotoxicity 2, 3, 6. The FDA labels explicitly state that methimazole is preferred in pediatric patients due to severe liver injury reports with PTU, and this maternal hepatotoxicity risk makes switching appropriate 2, 3.
Dosing Goals and Monitoring
Target FT4 in the high-normal range (upper third of reference range or just above normal) using the lowest possible thioamide dose 1, 7, 8. This approach minimizes fetal thyroid suppression while preventing maternal complications 1, 9.
Monitor thyroid function every 2-4 weeks by measuring FT4 or FTI (not TSH, which remains suppressed) 1, 7, 8. Adjust medication dosage based on FT4 levels, recognizing that many women experience spontaneous improvement as pregnancy progresses and may require dose reduction or discontinuation weeks before delivery 1, 2.
Symptomatic Management
Add propranolol or other beta-blockers for symptomatic relief (tachycardia, tremor, anxiety) until thioamide therapy reduces thyroid hormone levels 1. Beta-blocker doses may need reduction as the patient becomes euthyroid due to decreased clearance 2, 3.
Monitoring for Complications
Maternal Monitoring
Assess for signs of inadequate control at each visit: persistent tachycardia, excessive weight loss, hypertension 1. Untreated or inadequately treated hyperthyroidism increases risk of:
- Severe preeclampsia
- Heart failure
- Preterm delivery
- Miscarriage 1
Watch for thioamide adverse effects, particularly:
- Agranulocytosis: Instruct patients to report sore throat, fever, or general malaise immediately and obtain CBC with differential 1, 2, 3
- Hepatotoxicity (especially with PTU): Monitor for anorexia, pruritus, right upper quadrant pain 3
- Vasculitis: Report new rash, hematuria, decreased urine output, dyspnea, hemoptysis 2, 3
Fetal Monitoring
Monitor for fetal thyroid dysfunction in women with:
- High TRAb levels (check early in third trimester) 4, 5
- History of thyroid ablation or thyroidectomy with persistent antibodies 4
Perform fetal thyroid ultrasound when TRAb is elevated to assess for goiter 1, 4. Fetal thyroid function depends on the balance between transplacental maternal thyroid-stimulating antibodies and thyroid-inhibiting antithyroid drugs 4.
Adjust maternal medication if fetal hyperthyroidism is detected - maternal antithyroid drugs can treat fetal thyrotoxicosis 4.
Thyroid Storm Management
Recognize thyroid storm as a medical emergency characterized by: fever, tachycardia disproportionate to fever, altered mental status (nervousness, confusion, seizures), vomiting, diarrhea, cardiac arrhythmia, often with an inciting event (infection, labor, surgery) 1.
Treat immediately without waiting for confirmatory labs using:
- Propylthiouracil or methimazole
- Saturated solution of potassium iodide or sodium iodide (or Lugol's solution, lithium)
- Dexamethasone
- Phenobarbital
- Supportive care: oxygen, antipyretics, appropriate monitoring 1
Avoid delivery during thyroid storm unless absolutely necessary 1.
Surgical Considerations
Reserve thyroidectomy for women who do not respond to thioamide therapy or cannot tolerate medications 1.
Radioactive iodine (I-131) is absolutely contraindicated in pregnancy 1. If inadvertent exposure occurred before 10 weeks gestation, fetal thyroid ablation is unlikely; after 10 weeks, counsel regarding risk of congenital hypothyroidism and pregnancy continuation 1.
Neonatal Management
Measure cord blood TSH and T4 at delivery in all infants born to mothers with active Grave's disease or history of ablation with persistent antibodies 4.
Monitor newborns for thyrotoxicosis in the first days of life after maternal antithyroid drug clears, which can persist for months until maternal antibodies clear 4. Inform the pediatric team of maternal Grave's disease diagnosis 1.
Postpartum Considerations
Evaluate thyroid function 6 weeks postpartum as hyperthyroidism may recur as Grave's disease or postpartum thyroiditis 9.
Women can safely breastfeed while taking propylthiouracil or methimazole, as both are present in breast milk in clinically insignificant amounts 1, 2, 3. However, avoid breastfeeding for 4 months after I-131 treatment 1.
Key Pitfalls to Avoid
- Do not use TSH for monitoring treatment response - use FT4 or FTI every 2-4 weeks, as TSH remains suppressed during active disease 1, 7
- Do not continue methimazole through first trimester if pregnancy is planned - switch to PTU preconceptionally or immediately upon pregnancy recognition 2, 3, 6
- Do not over-treat - fetal/neonatal thyroid suppression from excessive maternal medication is usually transient but should be avoided 1
- Do not assume gestational transient thyrotoxicosis - biochemical hyperthyroidism with hyperemesis gravidarum rarely requires treatment, but true Grave's disease with clinical hyperthyroidism demands active management 1