What is the treatment of choice for a pregnant patient with a hyperthyroid (overactive thyroid) nodule?

From the Guidelines

The treatment of choice for a pregnant patient with a hyperthyroid nodule is typically propylthiouracil (PTU) during the first trimester, followed by methimazole for the remainder of pregnancy. This approach is based on the most recent and highest quality evidence, which suggests that PTU has less risk of rare congenital abnormalities compared to methimazole in early pregnancy 1. The typical starting dose of PTU is 100-150 mg three times daily, adjusted based on thyroid function tests, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 1.

Key Considerations

• After the first trimester, switching to methimazole (typically 10-20 mg daily) is recommended as it requires less frequent dosing and has better compliance 1.
• Regular monitoring of thyroid function every 2-4 weeks initially, then every 4-6 weeks once stabilized, is essential to maintain thyroid hormone levels in the low-normal range 1.
• The medication dose should be kept at the minimum effective level to avoid fetal hypothyroidism.
• Beta-blockers like propranolol may be used short-term for symptom control, as they can help reduce symptoms until thioamide therapy reduces thyroid hormone levels 1.
• Surgery is generally avoided during pregnancy unless absolutely necessary, and radioactive iodine is absolutely contraindicated due to the risk of fetal harm.

Potential Side Effects

• Agranulocytosis, a side effect of thioamides, usually presents with sore throat and fever, and requires immediate discontinuation of the medication and a complete blood cell count 1.
• Other side effects of thioamides include hepatitis, vasculitis, and thrombocytopenia, which should be monitored closely during treatment 1.

Importance of Treatment

Untreated hyperthyroidism poses significant risks to both mother and fetus, including preeclampsia, preterm birth, and fetal growth restriction, making it essential to achieve euthyroidism before pregnancy 1.

From the FDA Drug Label

In pregnant women with untreated or inadequately treated Graves’ disease, there is an increased risk of adverse events of maternal heart failure, spontaneous abortion, preterm birth, stillbirth and fetal or neonatal hyperthyroidism Because methimazole crosses placental membranes and can induce goiter and cretinism in the developing fetus, hyperthyroidism should be closely monitored in pregnant women and treatment adjusted such that a sufficient, but not excessive, dose be given during pregnancy Due to the rare occurrence of congenital malformations associated with methimazole use, it may be appropriate to use an alternative anti-thyroid medication in pregnant women requiring treatment for hyperthyroidism particularly in the first trimester of pregnancy during organogenesis. Given the potential maternal adverse effects of propylthiouracil (e.g., hepatotoxicity), it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters. Since methimazole may be associated with the rare development of fetal abnormalities propylthiouracil may be the preferred agent during the first trimester of pregnancy

The treatment of choice for a pregnant patient with a hyperthyroid nodule is propylthiouracil in the first trimester and methimazole in the second and third trimesters 2 3.

• Key considerations:
  • Monitor thyroid function closely
  • Adjust treatment to give a sufficient, but not excessive, dose
  • Be aware of the potential risks of congenital malformations and hepatotoxicity
• Alternative treatment: In some cases, it may be necessary to switch from one medication to the other due to adverse effects or other factors.

From the Research

Treatment Options for Hyperthyroidism in Pregnancy

• The treatment of choice for a pregnant patient with a hyperthyroid nodule depends on the trimester of pregnancy and the severity of the condition 4, 5.
• During the first trimester, propylthiouracil (PTU) is recommended due to its lower risk of congenital malformations compared to methimazole (MMI) 4, 5.
• In the second and third trimesters, low-dose MMI can be considered due to the risk of PTU-induced hepatotoxicity 4, 5.
• Radioactive iodine ablation and surgical thyroidectomy are generally avoided during pregnancy due to the risk of harming the fetus 6, 7.

Considerations for Treatment

• The choice of treatment should be individualized and based on the underlying diagnosis, presence of contraindications, severity of hyperthyroidism, and patient preference 6, 7.
• Antithyroid drugs, such as PTU and MMI, are commonly used to treat hyperthyroidism in pregnancy, but their use requires careful monitoring of maternal and fetal health 4, 5.
• Close monitoring is necessary to prevent disease complications or progression to overt hyperthyroidism, especially in cases of subclinical hyperthyroidism 8.

Risks and Complications

• Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes 7.
• PTU-induced hepatotoxicity is a rare but serious complication that can occur in approximately 0.1% of exposed adults 4, 5.
• MMI has been associated with an increased risk of congenital malformations, including ectodermal anomalies, choanal atresia, esophageal atresia, and omphalocele, although the absolute risk appears to be very small 4, 5.