How to manage hyperthyroidism in a pregnant lady in her third trimester with low Thyroid-Stimulating Hormone (TSH) and elevated Thyroxine (T4) levels while on methimazole (generic name) 5mg Once Daily (OD)?

Management of Third Trimester Hyperthyroidism on Methimazole with Suppressed TSH and Elevated T4

Immediate Action Required: Switch to Propylthiouracil

You should immediately switch from methimazole to propylthiouracil (PTU) for the remainder of this pregnancy, as methimazole carries significant teratogenic risks that persist throughout pregnancy, though the risk is highest in the first trimester. 1

While the critical period for methimazole-associated congenital malformations (aplasia cutis, choanal atresia, esophageal atresia, omphalocele) occurs primarily in the first trimester 1, continuing methimazole in the third trimester exposes the fetus to ongoing risks of fetal hypothyroidism and goiter, as methimazole readily crosses the placental membrane 1.

Current Thyroid Status Assessment

The patient's laboratory values indicate inadequately controlled hyperthyroidism:

• TSH 0.01 mIU/L (suppressed, indicating hyperthyroidism) 2
• T4 13.27 (assuming pmol/L, this is elevated above normal range of 9-19 pmol/L) 3
• Current dose of methimazole 5mg daily is insufficient 1

This represents overt hyperthyroidism with both suppressed TSH and elevated free T4, not subclinical disease 2. The severely suppressed TSH (<0.1 mIU/L) indicates active thyroid hormone excess 2.

Treatment Algorithm for Third Trimester

Step 1: Medication Switch (Within 24-48 Hours)

• Discontinue methimazole immediately 1
• Start PTU 100-150mg three times daily (total 300-450mg/day), as PTU is preferred in pregnancy despite hepatotoxicity risks because methimazole's teratogenic effects remain a concern 1
• PTU has lower placental transfer than methimazole, reducing fetal exposure 1

Step 2: Dose Titration Strategy

The goal is to maintain maternal free T4 at or slightly above the upper limit of normal to minimize fetal exposure to antithyroid drugs while preventing maternal thyrotoxicosis 1:

• Target maternal TSH will remain suppressed (0.1-1.0 mIU/L is acceptable in pregnancy) 1
• Target free T4 in the high-normal to slightly elevated range 1
• Use the lowest possible dose of antithyroid medication to achieve this target 1

Step 3: Monitoring Schedule

Monitor thyroid function tests every 2-4 weeks in the third trimester 1:

• Measure both TSH and free T4 1
• More frequent monitoring (every 2 weeks) is warranted given current inadequate control 1
• Adjust PTU dose based on free T4 levels, not TSH 1

Step 4: Fetal Monitoring

• Assess for fetal goiter via ultrasound if maternal hyperthyroidism remains poorly controlled 1
• Monitor fetal heart rate (fetal tachycardia >160 bpm suggests fetal hyperthyroidism) 1
• Coordinate with obstetrics for increased surveillance 1

Critical Pitfalls to Avoid

Pitfall 1: Continuing Methimazole

Never continue methimazole when PTU is available, as methimazole's teratogenic profile makes it inappropriate for pregnancy, particularly given the FDA's explicit warnings about congenital malformations 1. While the highest risk is in the first trimester, fetal goiter and hypothyroidism remain risks throughout pregnancy 1.

Pitfall 2: Overtreating to Normalize TSH

Do not increase antithyroid medication dose to normalize maternal TSH 1. In pregnancy, maternal TSH naturally runs lower, and aggressive treatment to normalize TSH will cause fetal hypothyroidism 1. The fetus depends on maternal thyroid hormone, especially in early pregnancy, and excessive antithyroid drugs cross the placenta more readily than thyroid hormone 1.

Pitfall 3: Undertreating Maternal Hyperthyroidism

Current control is inadequate with TSH 0.01 and elevated T4 2. Uncontrolled maternal hyperthyroidism increases risks of:

• Maternal heart failure 1
• Preterm birth 1
• Fetal/neonatal hyperthyroidism 1
• Stillbirth 1

Pitfall 4: Ignoring Thyroid Antibodies

If not already measured, check TSH receptor antibodies (TRAb or TSI) 4. High levels (>3 times upper limit of normal) in the third trimester predict neonatal hyperthyroidism and should prompt neonatal thyroid function testing at birth 4.

Special Considerations for Third Trimester

Postpartum Planning

• Many women experience worsening hyperthyroidism in the postpartum period as pregnancy-induced immunosuppression resolves 1
• Plan for close postpartum monitoring (TSH and free T4 at 2-4 weeks postpartum) 1
• PTU can be continued during breastfeeding with monitoring, as it has minimal breast milk transfer 1
• Consider definitive therapy (radioactive iodine or thyroidectomy) after breastfeeding is complete 1

Delivery Considerations

• Coordinate with anesthesia regarding potential for thyroid storm during labor 1
• Have beta-blockers available for maternal tachycardia management 2
• Ensure neonatal thyroid function testing is ordered at birth 1

Evidence Quality Considerations

The recommendation to switch from methimazole to PTU in pregnancy is based on FDA drug labeling (highest quality evidence for drug safety) 1. Methimazole carries a Pregnancy Category D designation, meaning there is positive evidence of human fetal risk 1. The FDA explicitly states that "it may be appropriate to use an alternative anti-thyroid medication in pregnant women requiring treatment for hyperthyroidism particularly in the first trimester of pregnancy during organogenesis" 1.

While some sources suggest methimazole may be acceptable in the second and third trimesters after switching from PTU 1, the current inadequate disease control and third trimester timing make PTU the safer choice for the remainder of this pregnancy 1.