How is hyperthyroidism (overactive thyroid) managed during pregnancy to minimize complications?

Management of Hyperthyroidism During Pregnancy

Antithyroid drugs (ATDs) are the primary treatment for hyperthyroidism in pregnancy, with propylthiouracil (PTU) preferred in the first trimester due to methimazole's teratogenic risk, then switching to methimazole for the second and third trimesters to avoid PTU's hepatotoxicity. 1, 2

First-Line Pharmacologic Management

First Trimester (Weeks 0-13)

• Use propylthiouracil (PTU) as the preferred agent during weeks 6-10 of pregnancy when organogenesis occurs, as methimazole exposure during this critical window can cause severe birth defects including aplasia cutis, choanal atresia, and esophageal atresia 1, 3
• PTU crosses the placenta minimally (0.025% into breast milk) compared to methimazole 4
• However, PTU carries significant hepatotoxicity risk including hepatic failure requiring transplantation or resulting in death 2

Second and Third Trimesters (Weeks 14-40)

• Switch from PTU to methimazole after the first trimester to minimize maternal hepatotoxicity risk while organogenesis is complete 1, 2
• Methimazole up to 30 mg/day is considered safe in later pregnancy 4
• Both drugs cross the placenta and can induce fetal goiter and hypothyroidism, requiring careful dose titration 1, 2

Treatment Goals and Monitoring Strategy

Target Thyroid Levels

• Maintain maternal free T4 (FT4) or free thyroxine index (FTI) in the high-normal range or just above normal using the lowest effective thioamide dose 4, 5
• This approach minimizes fetal thyroid suppression while controlling maternal hyperthyroidism 4
• Use free T4 and free T3 measurements rather than total levels, as total thyroid hormones are physiologically elevated in pregnancy due to increased thyroxine-binding globulin 6

Monitoring Frequency

• Check FT4 or FTI every 2-4 weeks during active treatment until stable 4
• Monitor every 4 weeks once TSH level is stable 7
• A rising TSH indicates excessive treatment and necessitates dose reduction 4
• Measure TSH suppression (undetectable TSH with elevated FTI) to confirm biochemical hyperthyroidism 7

Fetal Monitoring

• Assess thyroid receptor antibodies (TSI) in all hyperthyroid pregnant women to predict risk of fetal or neonatal thyroid dysfunction 5
• By 20 weeks' gestation, the fetal thyroid is fully responsive to both maternal TSI and antithyroid drugs 6
• Perform fetal ultrasound to evaluate for goiter if maternal disease is poorly controlled 7
• Transient neonatal TSH elevation may occur but typically normalizes without intervention 4

Symptomatic Management

• Use propranolol for symptomatic relief of tachycardia, tremor, and anxiety while awaiting thyroid hormone normalization 4
• Beta-blockers cross the placenta readily, so use the lowest effective dose 6
• Hyperthyroidism increases clearance of beta-blockers; dose reduction may be needed as the patient becomes euthyroid 1, 2

Critical Safety Monitoring

Agranulocytosis Risk

• Instruct patients to immediately report sore throat, fever, or signs of infection 4, 1, 2
• Obtain complete blood count immediately if agranulocytosis is suspected 4
• Discontinue thioamide immediately if confirmed 4

Other Serious Adverse Effects

• Monitor for vasculitis, hepatitis, and thrombocytopenia 4, 1, 2
• Patients should promptly report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis as these may indicate vasculitis 1, 2
• Check prothrombin time before surgical procedures as ATDs may cause hypoprothrombinemia 1, 2

Thyroid Storm Management

Thyroid storm is a life-threatening emergency requiring immediate treatment without waiting for confirmatory lab results. 7

Diagnostic Criteria

• Fever with tachycardia out of proportion to temperature elevation 7
• Altered mental status (nervousness, restlessness, confusion, seizures) 7
• Gastrointestinal symptoms (vomiting, diarrhea) 7
• Cardiac arrhythmia 7
• Often precipitated by infection, surgery, labor, or delivery 7

Treatment Protocol

• Administer standard drug series: propylthiouracil or methimazole; saturated solution of potassium iodide or sodium iodide (alternatives: Lugol's solution, lithium); dexamethasone; and phenobarbital 7
• Provide general supportive measures including oxygen, antipyretics, and appropriate monitoring 7
• Treat the underlying precipitating cause 7
• Avoid delivery during thyroid storm unless absolutely necessary 7
• Evaluate fetal status with ultrasound, nonstress testing, or biophysical profile depending on gestational age 7

Alternative Treatment Options

Thyroidectomy

• Reserve surgical thyroidectomy for patients who fail medical therapy, have large compressive goiters, or strongly prefer surgery 4
• If surgery is necessary, perform during the second trimester when safest 7
• Surgery carries risks of anesthesia complications and should be avoided during thyroid storm 7

Radioactive Iodine (I-131)

• Radioactive iodine is absolutely contraindicated during pregnancy and lactation 7, 4
• I-131 can induce congenital hypothyroidism if administered after fetal thyroid development 7
• Women must not breastfeed for 4 months after I-131 treatment 7, 4

Special Clinical Scenarios

Hyperemesis Gravidarum

• Nausea and vomiting of pregnancy is associated with biochemical hyperthyroidism (undetectable TSH, elevated FTI) mediated by high hCG levels 7, 8
• This condition rarely causes clinical hyperthyroidism and usually requires no treatment 7
• Routine thyroid testing is not recommended unless other signs of hyperthyroidism are present 7

Disease Course During Pregnancy

• Thyroid dysfunction often diminishes as pregnancy progresses, allowing dose reduction or even discontinuation of ATDs several weeks to months before delivery 1, 2, 5
• Graves' disease may improve during pregnancy due to maternal immune system changes 3
• Hyperthyroidism may recur postpartum as Graves' disease flares or as postpartum thyroiditis 5

Postpartum Considerations

• Evaluate thyroid function 6 weeks after delivery to detect postpartum thyroiditis or Graves' disease recurrence 5
• Postpartum thyroiditis occurs in 5-10% of women and many ultimately develop permanent hypothyroidism 8
• Diagnosis requires new onset of abnormal TSH or FT4 levels; antibody testing may confirm the diagnosis 7
• Risk of permanent hypothyroidism is greatest with highest TSH levels and antithyroid peroxidase antibodies 7

Screening Recommendations

• Screen pregnant women with symptoms of thyroid disease, history of thyroid disease, thyroid nodules, or goiter 7
• Universal screening is not currently recommended by ACOG, though some experts advocate for it given the association between maternal hypothyroidism and neuropsychological deficits in offspring 7, 9
• Look specifically for weight loss, eye signs, and thyroid bruit in pregnant women 6

Critical Pitfalls to Avoid

• Do not use methimazole during weeks 6-10 of pregnancy when birth defects are most likely to occur 1, 3
• Do not continue PTU beyond the first trimester due to severe hepatotoxicity risk 1, 2
• Do not over-treat with ATDs, as this causes fetal hypothyroidism and goiter; aim for maternal levels in the high-normal range 4, 5
• Do not administer radioactive iodine during pregnancy or within 4 months of breastfeeding 7, 4
• Do not delay treatment of thyroid storm while awaiting lab confirmation 7