What is the recommended management of hyperthyroidism in a pregnant woman, including diagnosis, treatment options for each trimester, monitoring, and postpartum care?

Management of Hyperthyroidism in Pregnancy

Use propylthiouracil (PTU) as first-line therapy during the first trimester, then switch to methimazole for the second and third trimesters to minimize both teratogenic risk and maternal hepatotoxicity. 1

Diagnostic Approach

Initial screening and confirmation:

• Measure TSH as the initial screening test; when hyperthyroidism is suspected, obtain both TSH and free T4 (FT4) or free thyroxine index (FTI) simultaneously 2, 1
• Diagnosis requires elevated FT4 or FTI with suppressed TSH in the absence of thyroid mass or nodular goiter 2, 1
• Critical pitfall: Always use trimester-specific TSH reference ranges to avoid misinterpretation and underdiagnosis 2

Clinical features to identify:

• Tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, hypertension, and goiter 2
• Distinctive signs specific to Graves' disease: eyelid lag or retraction, pretibial myxedema 2, 1
• Graves' disease accounts for approximately 95% of hyperthyroidism cases in pregnancy 2, 1

Additional testing for Graves' disease:

• Measure thyroid-stimulating hormone-receptor antibodies (TSH-receptor antibodies) in women with current or prior Graves' disease to guide management and assess fetal risk 1

Trimester-Specific Pharmacologic Management

First Trimester

Propylthiouracil (PTU) is the preferred agent:

• PTU carries lower risk of congenital malformations compared to methimazole during organogenesis 3, 1, 4
• Methimazole has been associated with rare congenital abnormalities including aplasia cutis, choanal atresia, and esophageal atresia 5, 4
• Use the lowest effective dose to maintain FT4 or FTI in the high-normal range 1

Second and Third Trimesters

Switch from PTU to methimazole:

• This switch minimizes maternal risk of PTU-associated hepatotoxicity, which can be severe and even fatal 3, 1, 4
• Continue targeting FT4 in the high-normal range with the lowest effective thioamide dose 1
• The teratogenic window has passed, making methimazole safer in later pregnancy 5, 4

Monitoring Protocol

Thyroid function monitoring:

• Check FT4 or FTI every 2-4 weeks initially to guide dose adjustments 1
• Once euthyroid status is achieved, measure TSH at least once each trimester 1
• Aim to keep FT4 in the high-normal range throughout pregnancy 1

Safety monitoring for thioamide therapy:

• Monitor complete blood count for agranulocytosis, especially if patient develops fever or sore throat 1, 5, 4
• Discontinue thioamide immediately if agranulocytosis is suspected 1, 5, 4
• Monitor for other rare adverse effects: hepatitis, vasculitis, thrombocytopenia 1, 4
• Check prothrombin time before surgical procedures due to potential vitamin K inhibition 5, 4

Fetal monitoring:

• Monitor fetal heart rate and growth throughout pregnancy 1
• Perform ultrasound for fetal goiter only if clinical concerns arise 1
• In women with TSH-receptor antibodies, assess risk of fetal thyrotoxicosis due to transplacental antibody passage 2, 1

Adjunctive Symptomatic Management

Beta-blocker therapy:

• Provide short-acting β-blockers (e.g., propranolol) for symptomatic control of tremor, tachycardia, or palpitations 1
• Continue only until thyroid hormone levels normalize 1
• Note that hyperthyroidism increases clearance of beta-blockers; dose reduction may be needed once euthyroid 5, 4

Special Clinical Scenarios

Hyperemesis Gravidarum

• Biochemical hyperthyroidism with undetectable TSH and elevated FT4 occurs due to high hCG levels in first trimester 2, 6
• Antithyroid therapy is rarely needed unless overt clinical signs of thyrotoxicosis are present 1
• Routine thyroid testing is not recommended for isolated hyperemesis 1

Thyroid Storm

Recognize as a medical emergency:

• Presents with fever, marked tachycardia, altered mental status, gastrointestinal symptoms, and arrhythmia 1, 7
• Mortality rate exceeds 10% 7
• Treat immediately without waiting for laboratory confirmation: use PTU or methimazole, inorganic iodide, dexamethasone, phenobarbital, and supportive care 1
• Avoid delivery unless absolutely necessary 1

Surgical Management

• Reserve thyroidectomy for patients who fail thioamide therapy or develop severe drug intolerance (agranulocytosis, hepatotoxicity) 1, 8
• If surgery is required, schedule in the second trimester 1

Absolute Contraindications

Radioactive iodine (I-131):

• Strictly contraindicated throughout pregnancy as it ablates the fetal thyroid after 10 weeks gestation 1, 8
• Women must wait at least 4 months after I-131 therapy before attempting pregnancy or breastfeeding 1

Maternal and Fetal Risks of Inadequate Treatment

Maternal complications:

• Severe preeclampsia, preterm delivery, maternal heart failure, miscarriage 2, 1, 9
• Thyroid storm (rare but life-threatening) 2, 7

Fetal and neonatal complications:

• Low birth weight, intrauterine growth restriction 2, 1, 9
• Fetal thyrotoxicosis from transplacental passage of TSH-receptor antibodies 2, 1
• Neonatal thyroid dysfunction (hyperthyroidism or hypothyroidism) requiring close monitoring 2, 1
• Transient fetal thyroid suppression from maternal thioamide therapy usually requires no specific treatment 1

Postpartum Care

Breastfeeding:

• Women treated with PTU or methimazole during pregnancy may breastfeed safely 1, 5, 4
• Both drugs are present in breast milk in clinically insignificant amounts 5, 4

Neonatal monitoring:

• Notify the newborn's care team of maternal Graves' disease to monitor for neonatal thyroid dysfunction 1
• Monitor thyroid function in neonates at frequent intervals if mother had TSH-receptor antibodies 1

Critical Pitfalls to Avoid

• Never postpone treatment while awaiting repeat thyroid tests—fetal harm can occur before maternal symptoms develop 1
• Never use methimazole in the first trimester when PTU is available due to higher teratogenic risk 3, 1
• Never continue PTU beyond the first trimester without switching to methimazole, given the risk of maternal hepatotoxicity 1, 4
• Never use radioactive iodine during pregnancy 1, 8
• Promptly evaluate any fever or sore throat with complete blood count and discontinue thioamide if agranulocytosis is suspected 1, 5, 4