How should the antithyroid drug regimen be managed in a woman of reproductive age with hyperthyroidism who wishes to become pregnant?

Management of Antithyroid Drugs in Women Planning Pregnancy

If a woman with hyperthyroidism wishes to become pregnant, she should ideally receive definitive treatment (thyroidectomy or radioactive iodine) before conception to avoid the risks of antithyroid drug exposure during pregnancy, but if antithyroid drugs must be continued, propylthiouracil (PTU) should be used exclusively during the first trimester, then switched to methimazole for the remainder of pregnancy. 1, 2

Preconception Strategy: Definitive Treatment First

The optimal approach is to offer definitive therapy (thyroidectomy or radioactive iodine ablation) to hyperthyroid women of childbearing potential before they attempt conception. 3 This strategy completely eliminates the risks of:

• Teratogenic drug exposure during organogenesis 4, 3
• Maternal hepatotoxicity from thionamides 2, 3
• Uncontrolled hyperthyroidism affecting the fetus 5, 6

Radioactive Iodine Timing

• Women must wait at least 4 months after radioactive iodine (I-131) treatment before attempting conception 2, 7
• I-131 is absolutely contraindicated once pregnancy occurs, as it causes fetal thyroid ablation 1, 2, 7

Thyroidectomy Considerations

• Thyroidectomy provides immediate resolution without radiation exposure 2, 7
• Women can attempt conception once thyroid hormone replacement is optimized post-operatively 2

If Antithyroid Drugs Must Be Continued

When definitive treatment is not feasible or the patient declines, the medication regimen must be carefully managed:

First Trimester (Weeks 1-13)

Use propylthiouracil (PTU) exclusively during the first trimester. 1, 2, 7, 6

• PTU carries lower risk of congenital malformations compared to methimazole 1, 6
• Methimazole exposure in the first trimester is associated with specific birth defects including choanal atresia, esophageal atresia, and aplasia cutis 6, 3
• Approximately 40% of women on low-dose antithyroid drugs (<10 mg methimazole equivalent) before conception can discontinue therapy during the first trimester 8

Second and Third Trimesters (Weeks 14-40)

Switch from PTU to methimazole after the first trimester is complete. 1, 2, 6

• This switch minimizes the risk of PTU-induced severe hepatotoxicity, which predominantly occurs with continued use beyond the first trimester 2, 3
• PTU-associated liver failure can be catastrophic during pregnancy, threatening both maternal and fetal survival 3
• Methimazole has a more favorable hepatic safety profile in the second and third trimesters 2, 6

Treatment Targets and Monitoring

Thyroid Function Goals

Maintain free T4 (or free thyroxine index) in the high-normal range using the lowest effective antithyroid drug dose. 2, 7

• The goal is mild maternal hyperthyroidism, not full euthyroidism, to prevent fetal thyroid suppression 2
• Targeting mid-normal or low-normal free T4 increases the risk of fetal hypothyroidism 2

Monitoring Schedule

• Check free T4 (or FTI) every 2-4 weeks throughout pregnancy to guide dose adjustments 1, 2, 7
• Once stable, check TSH every trimester 2
• A rising TSH indicates the need for a lower maintenance dose 9, 5

Critical Safety Monitoring

Agranulocytosis Warning

Instruct the patient to report sore throat or fever immediately. 2, 7, 5

• Obtain a complete blood count stat if these symptoms develop 2, 7
• Discontinue the thionamide immediately if agranulocytosis is confirmed 2, 7

Hepatotoxicity Surveillance

Monitor for signs of liver injury, particularly with PTU doses ≥300 mg/day, though hepatotoxicity can occur at doses as low as 50 mg/day. 2

• Symptoms include anorexia, pruritus, jaundice, light-colored stools, dark urine, and right upper quadrant pain 5
• Measure liver function tests (bilirubin, alkaline phosphatase) and hepatocellular enzymes (ALT/AST) if symptoms occur 5

Other Adverse Effects

• Monitor for vasculitis (new rash, hematuria, decreased urine output, dyspnea, hemoptysis) 9, 5
• Watch for thrombocytopenia 2
• Consider monitoring prothrombin time before surgical procedures due to potential vitamin K inhibition 9, 5

Adjunctive Symptom Management

Use beta-blockers (e.g., propranolol) temporarily to control tremor, palpitations, and tachycardia until antithyroid therapy lowers thyroid hormone levels. 2, 7

• Discontinue beta-blockers once biochemical control is achieved 2
• Avoid atenolol specifically, as it is associated with lower birth weight 1

Risks of Inadequate Treatment

Untreated or inadequately treated hyperthyroidism significantly increases maternal and fetal risks. 2, 7, 5, 6

Maternal complications include:

• Severe preeclampsia 2
• Heart failure 2, 5
• Thyroid storm 2, 7

Fetal/neonatal complications include:

• Spontaneous abortion 5, 6
• Preterm delivery 2, 5
• Stillbirth 7, 5
• Low birth weight 2
• Fetal or neonatal hyperthyroidism 5

Special Considerations

Women Already Well-Controlled Before Conception

Women treated for more than 6 months before conception have better outcomes. 8

• These women require lower antithyroid drug doses during pregnancy 8
• 40% can discontinue therapy in the first trimester (though 14.2% relapse) 8
• Up to 55% can discontinue therapy by the third trimester 8
• They experience fewer fetal complications compared to women diagnosed during pregnancy 8

Postpartum Planning

• Inform the newborn's physician about maternal hyperthyroidism to enable appropriate neonatal thyroid monitoring 2, 7
• Both PTU and methimazole are compatible with breastfeeding 2, 9
• Hyperthyroidism relapses postpartum in 83% of Graves' disease patients, typically at 3 months 8

Thyroidectomy During Pregnancy (Last Resort)

Reserve thyroidectomy only for women who fail antithyroid drug therapy or develop severe drug intolerance (agranulocytosis, marked hepatotoxicity). 2, 7

• If surgery is necessary, perform it during the second trimester to minimize fetal risk 1, 2, 7

Common Pitfalls to Avoid

• Do not continue PTU beyond the first trimester without switching to methimazole, as this increases maternal hepatotoxicity risk 2
• Do not target euthyroid or low-normal free T4 levels, as this causes fetal thyroid suppression; maintain high-normal range 2
• Do not use radioactive iodine during pregnancy under any circumstances 1, 2, 7
• Do not fail to counsel about definitive treatment options before conception, as this is the safest long-term strategy 3
• Do not assume thyroid function is stable; one-third of pregnancies show suboptimal thyroid status, particularly after definitive treatment 4