What is the recommended management of hyperthyroidism (excessive production of thyroid hormone) in pregnancy?

Management of Hyperthyroidism in Pregnancy

Propylthiouracil (PTU) is the preferred antithyroid drug during the first trimester of pregnancy, with consideration to switch to methimazole for the second and third trimesters to minimize maternal hepatotoxicity risk. 1, 2, 3

First-Line Pharmacologic Treatment

First Trimester Strategy

• Use propylthiouracil as the primary antithyroid medication during the first trimester because methimazole has been associated with rare congenital malformations during organogenesis. 1, 2, 3
• PTU crosses the placenta minimally and reduces the risk of fetal abnormalities compared to methimazole during early pregnancy. 2, 4

Second and Third Trimester Strategy

• Switch from PTU to methimazole after the first trimester due to the significant risk of severe maternal hepatotoxicity with PTU, including hepatic failure requiring transplantation or resulting in death. 1, 2, 3
• Methimazole becomes the safer option for maternal health once organogenesis is complete. 1, 3

Treatment Goals and Monitoring

Target Thyroid Levels

• Maintain maternal free T4 (FT4) or free thyroxine index (FTI) in the high-normal to slightly elevated range using the lowest effective thioamide dose to avoid fetal hypothyroidism. 5, 4
• Use free T4 and free T3 measurements rather than total hormone levels, as total T4 and T3 are physiologically elevated in pregnancy due to increased thyroxine-binding globulin. 4

Monitoring Schedule

• Check FT4 or FTI every 2-4 weeks during active treatment to ensure adequate control without overtreatment. 5
• A rising TSH level indicates excessive treatment and necessitates dose reduction to prevent fetal thyroid suppression. 5, 1
• Adjust levothyroxine requirements every 4 weeks if hypothyroidism develops, as thyroid hormone requirements frequently increase during pregnancy. 6

Symptomatic Management

• Use propranolol for symptomatic relief of tachycardia, tremor, and anxiety while awaiting normalization of thyroid hormone levels. 5
• Beta-blockers are effective for rate control, though doses may need adjustment as the patient becomes euthyroid due to increased clearance in hyperthyroid states. 6, 1

Critical Safety Monitoring

Immediate Reporting Requirements

• Instruct patients to immediately report sore throat, fever, pharyngitis, or any signs of infection as these may indicate agranulocytosis, a life-threatening complication. 5, 2
• Obtain complete blood count immediately and discontinue the thioamide if agranulocytosis is suspected. 5

Other Serious Adverse Effects

• Monitor for hepatitis (particularly with PTU), vasculitis, and thrombocytopenia. 5, 2
• PTU-associated vasculitis can result in severe complications and death; promptly evaluate new rash, hematuria, decreased urine output, dyspnea, or hemoptysis. 2
• Propylthiouracil should be discontinued immediately if patients develop tiredness, nausea, anorexia, fever, or malaise, with immediate liver function testing. 2

Prothrombin Time Monitoring

• Monitor prothrombin time during therapy, especially before surgical procedures, as both methimazole and PTU may cause hypoprothrombinemia and bleeding. 1, 2

Contraindicated Treatments

• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it crosses the placenta and causes fetal thyroid destruction and congenital hypothyroidism. 6, 5
• Women must not breastfeed for 4 months after I-131 treatment. 6, 5

Surgical Management

• Reserve thyroidectomy for patients who fail medical therapy, have large goiters causing compressive symptoms, or cannot tolerate antithyroid drugs. 5, 4
• If surgery is necessary, perform it preferably during the second trimester when anesthetic risks are lowest. 6

Special Considerations for Graves' Disease

Fetal and Neonatal Monitoring

• Inform the pediatrician of maternal Graves' disease due to risk of fetal/neonatal thyroid dysfunction from transplacental passage of thyroid-stimulating antibodies. 5, 7
• Thyroid-stimulating immunoglobulins (TSI) readily cross the placenta and can cause fetal hyperthyroidism, particularly after 20 weeks when the fetal thyroid becomes fully responsive. 4
• Fetal/neonatal thyroid suppression from thioamides is usually transient and rarely requires treatment. 5

Disease Course in Pregnancy

• Many pregnant women with Graves' disease experience improvement as pregnancy progresses, allowing dose reduction or even discontinuation of antithyroid drugs several weeks to months before delivery. 1, 2, 4

Gestational Transient Thyrotoxicosis (Hyperemesis Gravidarum)

• No treatment is usually required for biochemical hyperthyroidism associated with hyperemesis gravidarum, as it is rarely associated with clinical hyperthyroidism and resolves spontaneously. 6
• Routine thyroid testing is not recommended unless other signs of hyperthyroidism are present. 6

Thyroid Storm Management

• Thyroid storm is a medical emergency with high risk of maternal heart failure requiring immediate aggressive treatment without waiting for confirmatory laboratory results. 6
• Use a standard drug regimen: propylthiouracil or methimazole, saturated solution of potassium iodide or sodium iodide, dexamethasone, and phenobarbital. 6
• Provide supportive measures including oxygen, antipyretics, and appropriate monitoring. 6
• Avoid delivery during thyroid storm unless absolutely necessary, and evaluate fetal status with ultrasound, nonstress testing, or biophysical profile depending on gestational age. 6

Maternal and Fetal Risks of Untreated Hyperthyroidism

• Uncontrolled thyrotoxicosis significantly increases the risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal/neonatal hyperthyroidism. 1, 2, 7, 4
• Adequate treatment is essential to prevent these serious complications. 7, 8, 4