Hyperthyroidism In PregnancyEdit

Hyperthyroidism in pregnancy is a complex clinical state that intersects maternal health, fetal development, and obstetric management. Most cases during pregnancy arise from Graves' disease, but the condition can also reflect gestational changes driven by human chorionic gonadotropin (hCG) or maternal thyroid autoimmunity. Because thyroid hormones play a critical role in fetal brain development, timing and intensity of treatment matter for both mother and child. Proper diagnosis and carefully chosen therapy aim to keep maternal free thyroid hormone in the normal range while minimizing fetal exposure to medications with potential adverse effects thyroid-stimulating hormone signaling and other risks. See also pregnancy and Graves' disease for related context.

Pathophysiology and etiologies

• Graves' disease is the most common cause of persistent hyperthyroidism in pregnant women. In this condition, autoantibodies stimulate the TSH receptor, increasing thyroid hormone production. Some of these autoantibodies can cross the placenta and stimulate the fetal thyroid, potentially causing fetal thyrotoxicosis if levels are high TSH receptor antibodies.
• Gestational thyrotoxicosis refers to transient hyperthyroidism driven by high circulating levels of hCG, particularly in the first trimester. hCG can weakly stimulate the fetal thyroid axis, leading to maternal thyrotoxicosis without underlying autoimmune disease. This form often resolves as hCG levels fall later in pregnancy.
• Subclinical hyperthyroidism during pregnancy—where TSH is suppressed but free T4 remains normal—has a different risk profile and typically requires different management than overt hyperthyroidism.
• Iodine status and the overall hormonal milieu of pregnancy (including estrogen-induced increases in thyroid-binding globulin) alter thyroid hormone levels and the interpretation of laboratory tests, making clinical context essential for diagnosis and monitoring iodine and pregnancy physiology.

Diagnosis

• Clinical features can include tachycardia, weight loss, heat intolerance, tremor, and anxiety, but many symptoms overlap with normal pregnancy. Objective testing is essential.
• Laboratory tests typically show suppressed or undetectable TSH with elevated free thyroxine (free T4) or, less commonly, elevated free triiodothyronine (free T3). In early pregnancy, trimester-specific reference ranges help avoid misclassification due to physiologic changes in thyroid function.
• Autoantibodies are especially relevant in Graves' disease. Detecting TSH receptor antibodies helps assess risk of fetal thyrotoxicosis and guides decisions about fetal monitoring.
• Fetal assessment may include Doppler ultrasound for fetal heart rate and growth trends in pregnancies at higher risk (e.g., maternal Graves’ disease with high TRAb). In some cases, fetal thyroid status can be inferred from neonatal screening after birth.
• Distinguishing Graves' disease–related hyperthyroidism from gestational thyrotoxicosis is important for management, because the fetal risk profile and treatment strategy differ. See gestational thyrotoxicosis for comparison.

Management principles

• The goal is to maintain maternal thyroid hormone in the upper-normal or mid-normal range for pregnancy, avoiding both maternal thyrotoxicosis and iatrogenic hypothyroidism, which can also harm fetal development.
• Antithyroid drugs are the mainstay of therapy for most pregnant patients with overt hyperthyroidism arising from autoimmune disease or persistent disease:
  • Propylthiouracil (PTU) has been preferred in the first trimester due to concerns about methimazole (MMI)–related congenital anomalies. PTU carries a risk of liver toxicity and transaminase elevation, so the lowest effective dose is sought and therapy is reassessed regularly.
  • Methimazole (MMI) is commonly used in the second and third trimesters to reduce the risk of PTU-induced hepatotoxicity, with careful monitoring to avoid overtreatment.
  • The choice and sequence of PTU then MMI dosing should be individualized, and in many guidelines the practice is to use PTU in the first trimester and switch to MMI in the second trimester, with reevaluation as pregnancy progresses. Some high-risk patients with severe disease may continue PTU beyond the first trimester if clinically necessary.
  • Dosing is titrated to achieve a normal maternal free T4 level while avoiding maternal hypothyroidism. Regular monitoring of TSH and free T4 is essential, and adjustments are often needed as pregnancy progresses and placental transfer of hormones changes.
• Beta-blockers such as propranolol may be used temporarily to control tachycardia or tremor, especially in severe cases. However, they cross the placenta and can be associated with fetal effects if used long term; short-term use with careful fetal monitoring is sometimes warranted.
• Iodine therapy is generally avoided during pregnancy for treatment of maternal hyperthyroidism due to potential fetal thyroid dysfunction; iodine is essential for the fetal thyroid, but excess or deficient exposure can cause problems.
• Radioactive iodine therapy is contraindicated during pregnancy because it crosses the placenta and permanently damages the fetal thyroid; treatment planning must occur before conception if active disease is present.
• In mothers with Graves' disease, maternal TRAb levels guide risk assessment for fetal thyrotoxicosis. If TRAb levels are high, the fetus may require closer monitoring and, in some cases, in-utero therapy or earlier neonatal assessment after birth. See neonatal thyrotoxicosis for related outcomes.
• Delivery planning and postpartum management depend on disease activity and maternal thyroid status. Thyroid function often improves after delivery as hCG levels fall, but thyroid hormone management may need to be adjusted in the postpartum period.

Fetal and neonatal considerations

• Fetal thyrotoxicosis can occur when maternal TSH receptor-stimulating antibodies cross the placenta. It may present with tachycardia, growth restriction, hydrops, and fetal distress. Early recognition and treatment of the mother can mitigate fetal effects, but neonatal thyroid function should be checked after birth in at-risk infants.
• Fetal hypothyroidism is less common in the setting of maternal hyperthyroidism but remains a consideration when antithyroid drugs cross the placenta in higher doses.
• Neonatal screening for thyroid function is used to identify and promptly treat any neonatal thyroid dysfunction, reducing long-term neurodevelopmental risk.

Controversies and debates

• Screening in pregnancy: There is ongoing debate about universal versus targeted screening for thyroid disease in pregnancy. Some clinicians advocate screening all pregnant patients to identify subclinical disease that might affect outcomes, while others emphasize cost-effectiveness and the risk of overdiagnosis. Guidelines vary by country and professional society, with some endorsing targeted screening based on risk factors and clinical signs.
• Treatment thresholds: The decision of what constitutes an indication to treat subclinical disease, or how aggressively to treat borderline cases, remains debated. Proponents argue that overtreatment carries drug-related risks, while opponents worry about missing clinically significant disease that could harm fetal development.
• Antithyroid drug safety: The long-standing debate about the teratogenic risk of MMI in the first trimester versus PTU-associated liver toxicity continues. Clinicians weigh the comparative risks and tailor treatment to individual patient circumstances, weighing fetal outcomes and maternal safety.
• Fetal monitoring intensity: The optimal level of fetal surveillance for pregnancies affected by maternal hyperthyroidism is not universally fixed. Some care pathways advocate for targeted fetal monitoring in pregnancies with high TRAb titers or poor maternal control, while others reserve intensive monitoring for overt fetal signs of thyroid dysfunction.

See also

• Graves' disease
• gestational thyrotoxicosis
• thyroid-stimulating hormone
• free T4
• antithyroid drugs (e.g., propylthiouracil, methimazole)
• neonatal thyrotoxicosis
• thyroid receptor antibodies
• radioactive iodine (contraindicated in pregnancy)
• thyroid function tests
• American Thyroid Association