What is the recommended management of Graves disease in pregnancy?

Management of Graves' Disease in Pregnancy

Treat Graves' disease in pregnancy with propylthiouracil (PTU) 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, 2, 3

Diagnosis and Confirmation

• Confirm Graves' disease by measuring TSH (suppressed) and free T4 or free thyroxine index (FTI) (elevated), ensuring no thyroid nodules are present. 1

• Look for distinctive clinical features that distinguish pathologic hyperthyroidism from normal pregnancy changes: 1

  • Eyelid lag or retraction
  • Pretibial myxedema
  • Thyroid bruit
  • Tremors
  • Excessive sweating beyond typical pregnancy changes
  • Tachycardia out of proportion to gestational age

• Measure thyrotropin receptor antibodies (TRAb) in all women with Graves' disease, as elevated levels (e.g., >200 IU/L) predict fetal and neonatal thyrotoxicosis risk and guide treatment decisions. 4, 5

Medical Management Algorithm

First Trimester (Weeks 1-13)

• Use propylthiouracil (PTU) as the preferred agent because methimazole carries a risk of congenital malformations during organogenesis. 1, 2

• PTU is preferred despite its hepatotoxicity risk because methimazole-associated birth defects (aplasia cutis, choanal atresia, esophageal atresia) occur during this critical period. 2, 3

Second and Third Trimesters (Weeks 14-40)

• Switch from PTU to methimazole after the first trimester due to PTU's risk of severe maternal hepatotoxicity, including liver failure requiring transplantation. 1, 3

• Methimazole allows once-daily dosing, improving adherence, and has lower hepatotoxicity risk after organogenesis is complete. 2, 6

Dosing Strategy Throughout Pregnancy

• Target free T4 in the high-normal range (upper third of reference range or just above normal) using the lowest possible thioamide dose to minimize fetal thyroid suppression while preventing maternal complications. 1, 7

• Monitor free T4 or FTI every 2-4 weeks initially, then every trimester once stable. 4

• Adjust dosage based on free T4 levels, not TSH, as TSH may remain suppressed even with adequate treatment. 1

Adjunctive Symptom Management

• Use beta-blockers (propranolol) temporarily to control symptoms like palpitations and tachycardia until thioamide therapy reduces thyroid hormone levels. 4, 6

• Beta-blocker dosage may need reduction as the patient becomes euthyroid due to decreased clearance. 2

Monitoring for Maternal Complications

• Assess for signs of inadequate control at each visit: 1

  • Persistent tachycardia (heart rate >100 bpm at rest)
  • Excessive weight loss
  • Hypertension
  • Tremors or heat intolerance

• Untreated or inadequately treated hyperthyroidism increases risk of severe preeclampsia, preterm delivery, miscarriage, and maternal heart failure. 1, 2

• Monitor for thioamide side effects: 2, 3

  • Agranulocytosis: sore throat, fever (obtain white blood cell count immediately)
  • Hepatotoxicity: nausea, vomiting, right upper quadrant pain, dark urine, jaundice
  • Vasculitis: new rash, hematuria, decreased urine output, dyspnea

Fetal and Neonatal Considerations

• Women with elevated TRAb levels require continued treatment throughout pregnancy regardless of current thyroid status to prevent fetal and neonatal thyrotoxicosis from transplacental antibody passage. 4

• Monitor fetal heart rate and growth; inform the newborn's physician about maternal Graves' disease due to risk of neonatal immune-mediated hyperthyroidism or hypothyroidism. 4, 7

• Fetal thyroid suppression from maternal thioamide therapy is usually transient and rarely requires treatment, making benefits of maternal treatment outweigh this risk. 4

Thyroid Storm Management

• Recognize thyroid storm as a medical emergency characterized by: 1

  • Fever
  • Tachycardia disproportionate to fever
  • Altered mental status (nervousness, restlessness, confusion, seizures)
  • Vomiting and diarrhea
  • Cardiac arrhythmia

• Treat immediately without waiting for confirmatory labs using: 1

  • Propylthiouracil or methimazole
  • Saturated solution of potassium iodide or sodium iodide (alternatives: Lugol's solution, lithium)
  • Dexamethasone
  • Phenobarbital
  • General supportive measures (oxygen, antipyretics, appropriate monitoring)

• Avoid delivery during thyroid storm unless deemed necessary; evaluate fetal status with ultrasound, nonstress testing, or biophysical profile depending on gestational age. 8

Surgical Considerations

• Reserve thyroidectomy for women who do not respond to thioamide therapy or cannot tolerate medications. 1

• If surgery is necessary, perform preferably during the second trimester when surgical risk is lowest. 8

• Radioactive iodine (I-131) is absolutely contraindicated in pregnancy as it damages the fetal thyroid gland, causing fetal hypothyroidism. 1, 6

Postpartum Management

• Evaluate thyroid function 6 weeks postpartum as hyperthyroidism may recur as Graves' disease or postpartum thyroiditis. 1, 7

• Women can safely breastfeed while taking propylthiouracil or methimazole, as both are present in breast milk in clinically insignificant amounts. 1, 2

• Monitor thyroid function at frequent (weekly or biweekly) intervals in nursing infants if concerned, though long-term studies of 139 thyrotoxic lactating mothers found no toxicity in nursed infants. 2

Critical Pitfalls to Avoid

• Do not use both PTU and methimazole simultaneously in early pregnancy, as exposure to both antithyroid drugs increases congenital malformation risk compared to either agent alone. 5

• Do not aim for low-normal free T4 levels, as this increases risk of fetal hypothyroidism and goiter development from overtreatment. 9

• Do not rely on TSH levels alone for monitoring, as TSH may remain suppressed throughout pregnancy even with adequate treatment. 1

• Do not discontinue treatment based solely on maternal euthyroid status if TRAb levels remain elevated, as fetal thyrotoxicosis risk persists. 4