What is the recommended management for 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 effective dose. 1, 2, 3

Diagnosis and Confirmation

• Confirm Graves' disease by measuring TSH (suppressed) and free T4 (elevated), looking specifically for distinctive clinical features including eyelid lag/retraction, pretibial myxedema, and thyroid bruit. 1

• Distinguish pathologic hyperthyroidism from normal pregnancy by identifying tremors, excessive sweating beyond typical pregnancy changes, and tachycardia disproportionate to gestational age. 1

• Avoid confusing Graves' disease with gestational transient thyrotoxicosis (hyperemesis gravidarum-associated), which presents with biochemical hyperthyroidism but rarely requires treatment and resolves spontaneously. 4

First-Line Medical Management: Thioamide Therapy

First Trimester Strategy

• Use propylthiouracil (PTU) as the preferred agent during the first trimester because methimazole carries a documented risk of congenital malformations including aplasia cutis, choanal atresia, and esophageal atresia. 1, 2, 5

• Target free T4 in the high-normal range using the lowest possible PTU dose to minimize fetal thyroid suppression while preventing maternal complications including heart failure, preeclampsia, preterm delivery, and miscarriage. 1, 6

Second and Third Trimester Strategy

• Switch from PTU to methimazole after the first trimester due to PTU's risk of severe maternal hepatotoxicity, which can progress to hepatic failure requiring liver transplantation. 1, 2, 3

• Continue methimazole at the lowest effective dose throughout the remainder of pregnancy, as methimazole is safer for the mother after organogenesis is complete. 1, 3

Critical Dosing Principles

• Aim for maternal free T4 at the upper limit of normal or even slightly elevated rather than mid-normal range, because antithyroid drugs block fetal thyroid function more effectively than maternal thyroid function. 7, 8

• Reduce PTU/methimazole dosage progressively as pregnancy advances, anticipating the customary amelioration of hyperthyroidism that occurs in later stages of pregnancy. 6

• Discontinue antithyroid drugs entirely in approximately one-third of patients during the second half of pregnancy if thyroid function normalizes. 6

Monitoring Protocol

• Assess thyroid function and clinical status every 3 weeks if progress is satisfactory, more frequently if control is inadequate. 6

• Monitor for signs of inadequate control at each visit, including persistent tachycardia, excessive weight loss, and hypertension. 1

• Obtain white blood cell count with differential immediately if the patient develops sore throat, fever, skin eruptions, or general malaise to detect agranulocytosis. 2, 3

• Monitor prothrombin time before surgical procedures as thioamides may cause hypoprothrombinemia and bleeding. 2, 3

Thyroid Storm Management

• Recognize thyroid storm as a medical emergency characterized by fever, tachycardia disproportionate to fever, altered mental status (nervousness, restlessness, confusion, seizures), vomiting, diarrhea, and cardiac arrhythmia. 4, 1

• Initiate treatment immediately without waiting for confirmatory laboratory results using a standard drug regimen: propylthiouracil or methimazole, saturated solution of potassium iodide or sodium iodide, dexamethasone, and phenobarbital. 4, 1

• Provide general supportive measures including oxygen, antipyretics, and appropriate monitoring while treating the underlying precipitating cause (surgery, infection, labor, delivery). 4

• Avoid delivery during thyroid storm unless deemed absolutely necessary, and evaluate fetal status with ultrasound, nonstress testing, or biophysical profile depending on gestational age. 4

Surgical Considerations

• Reserve thyroidectomy exclusively for women who do not respond to thioamide therapy or cannot tolerate medications, as surgery during pregnancy carries significant risks. 1

• Avoid surgical thyroidectomy in pregnant women with active Graves' disease because the combination of thyroidectomy, withdrawal of antithyroid medication, and levothyroxine replacement creates a high risk of isolated fetal hyperthyroidism due to persistent maternal TSH-receptor antibodies crossing the placenta. 7

• If surgery is absolutely necessary, perform thyroidectomy during the second trimester when risks are lowest. 9

• Radioactive iodine (I-131) is absolutely contraindicated in pregnancy and should not be administered until after delivery. 4, 1, 9

Postpartum Management

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

• Counsel patients that breastfeeding is safe while taking propylthiouracil or methimazole at the lowest effective dose, as both drugs are present in breast milk in clinically insignificant amounts. 1, 2, 3

• Consider definitive treatment with radioactive iodine or surgery postpartum to prevent recurrent episodes of pregnancy complicated by hyperthyroidism in future pregnancies. 6

Critical Pitfalls to Avoid

• Do not aim for mid-normal maternal thyroid function, as this approach risks fetal hypothyroidism because antithyroid drugs cross the placenta more effectively than maternal thyroid hormone. 7

• Do not add levothyroxine to antithyroid drug therapy (block-replace regimen) during pregnancy, as levothyroxine has limited placental transfer and will not adequately protect the fetus from hypothyroidism. 7

• Do not continue PTU beyond the first trimester due to hepatotoxicity risk, and do not use methimazole during the first trimester due to teratogenicity risk. 1, 2, 3

• Do not prescribe more than a 3-week supply of antithyroid drugs to ensure patients return for monitoring and prevent unsupervised continuation of therapy. 6