How is hyperthyroidism (elevated thyroid hormone levels) with low Thyroid-Stimulating Hormone (TSH) levels managed during pregnancy?

Management of Hyperthyroidism with Low TSH During Pregnancy

Hyperthyroidism in pregnancy should be treated with antithyroid drugs (thionamides), using propylthiouracil (PTU) in the first trimester and switching to methimazole for the second and third trimesters, with the goal of maintaining free T4 in the high-normal range using the lowest possible medication dose. 1, 2

Initial Assessment and Diagnosis

• Distinguish true hyperthyroidism from gestational transient thyrotoxicosis, which occurs in 1-2% of pregnancies and is typically associated with hyperemesis gravidarum, mediated by high human chorionic gonadotropin levels 1, 3
• Gestational transient thyrotoxicosis rarely requires treatment and usually resolves spontaneously 1
• Measure TSH, free T4 (or free thyroxine index), and free T3 to confirm biochemical hyperthyroidism (undetectable TSH with elevated free T4/T3) 1
• If clinical hyperthyroidism is present beyond nausea and vomiting, antithyroid drug treatment is indicated 1

Treatment Algorithm with Antithyroid Drugs

First Trimester Management

• Start propylthiouracil (PTU) as the preferred agent in the first trimester to avoid the rare but serious congenital malformations (choanal and esophageal atresia) associated with methimazole/carbimazole exposure during organogenesis 1, 4, 5
• PTU is preferred despite its hepatotoxicity risk because the teratogenic risk of methimazole is highest during the first trimester 4, 6, 5

Second and Third Trimester Management

• Switch from PTU to methimazole after the first trimester (around 12-16 weeks gestation) to minimize the risk of PTU-induced severe hepatotoxicity, which can be catastrophic in pregnancy with risk of liver failure 4, 6, 5
• Methimazole becomes the preferred agent after organogenesis is complete 4, 5

Dosing and Monitoring Strategy

• Use the lowest possible thioamide dose to maintain free T4 or free thyroxine index in the high-normal range (upper one-third of the trimester-specific reference range) 1, 2, 5
• Avoid overtreatment, as this can induce fetal hypothyroidism and goiter since antithyroid drugs cross the placenta 1, 4
• Monitor free T4 (or free thyroxine index) every 2-4 weeks during dose titration 1
• Once stable, check thyroid function every trimester to adjust dosing as needed 1, 2
• Many pregnant women experience spontaneous improvement in hyperthyroidism as pregnancy progresses, allowing dose reduction or even discontinuation several weeks to months before delivery 4, 5

Critical Considerations and Risks

Maternal Risks of Untreated Hyperthyroidism

• Untreated or inadequately treated maternal hyperthyroidism increases risk of severe preeclampsia, preterm delivery, heart failure, miscarriage, and spontaneous abortion 1, 4, 3
• Thyroid storm is a life-threatening emergency occurring in less than 1% of pregnant women with hyperthyroidism, characterized by fever, tachycardia disproportionate to fever, altered mental status, vomiting, diarrhea, and cardiac arrhythmia 1

Fetal and Neonatal Risks

• Low birth weight can occur with inadequately treated maternal hyperthyroidism 1
• Fetal thyrotoxicosis must be considered in women with current or past Graves' disease due to transplacental passage of thyroid-stimulating antibodies 1, 3
• Neonatal hyperthyroidism or hypothyroidism can occur due to maternal antibodies or antithyroid drug effects 1, 5
• Fetal thyroid status should be evaluated with ultrasound (looking for goiter, growth restriction, hydrops) and appropriate consultation sought if fetal thyrotoxicosis is suspected 1, 3

Drug-Specific Adverse Effects

• PTU carries risk of severe hepatotoxicity that can progress to liver failure in pregnancy, though this is uncommon 6, 5
• Methimazole/carbimazole exposure in the first trimester is associated with congenital malformations including choanal atresia, esophageal atresia, and aplasia cutis 4, 6, 5
• Both drugs can induce fetal goiter and cretinism if maternal dosing is excessive 4

Management of Thyroid Storm in Pregnancy

• Do not delay treatment while awaiting laboratory confirmation—diagnosis is clinical based on fever, severe tachycardia, altered mental status, and an inciting event (surgery, infection, labor) 1
• Standard drug regimen includes: propylthiouracil or methimazole; saturated solution of potassium iodide or sodium iodide; dexamethasone; and phenobarbital 1
• Provide supportive care with oxygen, antipyretics, and appropriate monitoring 1
• Treat the underlying precipitating cause 1
• Avoid delivery during thyroid storm unless absolutely necessary 1
• Monitor fetal status with ultrasound, nonstress testing, or biophysical profile depending on gestational age 1

Special Situations

Beta-Blocker Use

• Until thioamide therapy reduces thyroid hormone levels, a beta-blocker may be used for symptomatic control of tachycardia and tremor 1
• Be aware that beta-blocker dosing may need reduction as the patient becomes euthyroid due to decreased clearance 4

Breastfeeding

• Both methimazole and propylthiouracil are compatible with breastfeeding 1, 4
• Long-term studies of nursing infants whose mothers received methimazole showed no toxicity 4
• Monitor infant thyroid function at frequent (weekly or biweekly) intervals if the mother is taking antithyroid drugs 4

Preconception Counseling

• Women with known hyperthyroidism should ideally achieve euthyroid status before conception 7
• Consider definitive treatment (thyroidectomy or radioactive iodine) before pregnancy in appropriate candidates to avoid antithyroid drug exposure during pregnancy 6, 7
• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy and lactation and can cause fetal hypothyroidism if exposure occurs after the first trimester 1
• Women should not breastfeed for 4 months after I-131 treatment 1

Common Pitfalls to Avoid

• Do not perform routine thyroid testing in pregnant women with only nausea and vomiting unless other signs of hyperthyroidism are present 1
• Avoid using methimazole/carbimazole during the first trimester when PTU is available 4, 6, 5
• Do not continue PTU beyond the first trimester due to hepatotoxicity risk—switch to methimazole 4, 6, 5
• Avoid overtreating maternal hyperthyroidism, as this can induce fetal hypothyroidism 1, 4
• Do not miss the diagnosis of fetal thyrotoxicosis in women with Graves' disease, as this requires urgent treatment via maternal antithyroid drug administration 1, 3
• Ensure adequate monitoring frequency—thyroid function can change rapidly during pregnancy and requires assessment every 2-4 weeks during active management 1, 2