In a first‑trimester pregnant patient with hyperthyroidism or thyroid storm, should propylthiouracil (PTU) or methimazole be used?

Propylthiouracil (PTU) is the Preferred Agent During First Trimester Pregnancy and Thyroid Storm

For first-trimester pregnant patients with hyperthyroidism or thyroid storm, propylthiouracil (PTU) should be used as the primary antithyroid medication. 1

First Trimester Pregnancy Management

PTU as First-Line Agent

• PTU is recommended during the first trimester due to lower risk of congenital abnormalities compared to methimazole 1
• Meta-analysis confirms pregnant women treated with methimazole had significantly higher risk of congenital anomalies than those treated with PTU (OR 0.80,95%CI 0.69-0.92, P = 0.002) 2
• Methimazole has been associated with rare but specific teratogenic effects including choanal atresia and a characteristic pattern of birth defects (MMI embryopathy) when used in the first trimester 3

Switching Strategy After First Trimester

• Consider switching from PTU to methimazole for the second and third trimesters 1, 4
• This approach balances the teratogenic risk of methimazole in early pregnancy against the hepatotoxic risk of prolonged PTU exposure 3, 5
• The FDA drug label explicitly states: "Given the potential for maternal hepatotoxicity from propylthiouracil, it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters during pregnancy" 4

Important Caveat on Placental Transfer

• Both PTU and methimazole cross the placenta equally 6
• A perfused human placental lobule study demonstrated similar transfer kinetics for both drugs, with no significant difference in clearance rates 6
• The traditional belief that PTU crosses the placenta less freely than methimazole is not supported by pharmacokinetic evidence 6
• The preference for PTU is based on teratogenic risk, not placental transfer differences 6, 3

Thyroid Storm Management

PTU in Emergency Settings

• Thyroid storm is a medical emergency requiring immediate treatment with PTU or methimazole without waiting for laboratory confirmation 1
• Treatment includes PTU or methimazole, potassium/sodium iodide solutions, dexamethasone, phenobarbital, and supportive care 1
• PTU is specifically indicated for thyroid storm in adults, representing one of the few situations where PTU remains appropriate outside of first-trimester pregnancy 5, 7

Avoid Delivery During Thyroid Storm

• Delivery should be avoided during thyroid storm unless absolutely necessary 1
• Stabilize the mother's thyroid status before proceeding with delivery when possible 1

Dosing and Monitoring Strategy

Treatment Goals

• Maintain free T4 or free thyroxine index (FTI) in the high-normal range using the lowest possible thioamide dosage 1
• Use the minimum effective dose to avoid fetal hypothyroidism and goiter 4

Monitoring Schedule

• Monitor free T4 or FTI every 2-4 weeks to guide dosage adjustments 1
• Check TSH level once each trimester 1
• In many pregnant women, thyroid dysfunction diminishes as pregnancy proceeds, allowing dose reduction or discontinuation several weeks before delivery 4

Adjunctive Therapy

• Beta-blockers (e.g., propranolol) can be used temporarily to manage symptoms like tremors and palpitations until thioamide therapy reduces thyroid hormone levels 1
• Beta-blockers should only be used when overt hyperthyroid symptoms develop, not for purely biochemical abnormalities 8

Critical Safety Considerations

Hepatotoxicity Risk with PTU

• PTU carries a risk of severe hepatic failure, particularly with prolonged use 4, 5, 7
• The FDA issued a black box warning for PTU-related hepatotoxicity in 2009 5, 7
• In adult cases, PTU-induced liver injury occurred after relatively long treatment periods (4 months to >1 year) in 64% of cases 5
• This hepatotoxicity risk is the primary reason to switch to methimazole after the first trimester 4, 3

Monitoring for Adverse Effects

• Monitor for agranulocytosis (presenting with sore throat and fever), hepatitis, vasculitis, and thrombocytopenia 1, 4
• The FDA drug label warns: "Inform patients to promptly report symptoms that may be associated with vasculitis including new rash, hematuria or decreased urine output, dyspnea or hemoptysis" 4
• If patients develop tiredness, nausea, anorexia, fever, pharyngitis, or malaise, PTU should be discontinued immediately and liver function tests obtained 4

Fetal and Neonatal Considerations

• Inform the newborn's physician about maternal Graves' disease due to risk of neonatal thyroid dysfunction 1
• PTU crosses placental membranes and can induce goiter and cretinism in the developing fetus if excessive doses are used 4
• Fetal monitoring should include assessment for normal heart rate and appropriate growth 8

Special Clinical Scenarios

Hyperemesis Gravidarum with Biochemical Hyperthyroidism

• Antithyroid drugs are NOT recommended for hyperemesis gravidarum with isolated biochemical hyperthyroidism (no overt symptoms) 8
• This represents transient gestational thyrotoxicosis that resolves spontaneously with treatment of vomiting 8
• Beta-blockers should only be used if overt hyperthyroid symptoms develop (tachycardia disproportionate to dehydration, tremor, heat intolerance) 8

When Surgery is Necessary

• Thyroidectomy should be reserved for women who do not respond to thioamide therapy or develop intolerance (agranulocytosis, severe hepatotoxicity) 1
• If surgery is necessary, the second trimester is the preferred timing 1
• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy 1

Risks of Inadequate Treatment

• Untreated or inadequately treated hyperthyroidism increases risks of preeclampsia, preterm delivery, heart failure, miscarriage, low birth weight, and fetal thyroid dysfunction 1, 4
• In pregnant women with untreated or inadequately treated Graves' disease, there is increased risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal or neonatal hyperthyroidism 4

Breastfeeding Considerations

• Women treated with PTU or methimazole can breastfeed safely 1
• PTU is present in breast milk to a small extent, resulting in clinically insignificant doses to the nursing infant (mean 0.025% of administered dose excreted in 4 hours) 4

Common Pitfalls to Avoid

• Do not use methimazole in the first trimester due to teratogenic risk 1, 3, 2
• Do not continue PTU throughout entire pregnancy without considering switch to methimazole after first trimester 1, 4, 3
• Do not treat hyperemesis gravidarum with biochemical hyperthyroidism using antithyroid drugs 8
• Do not use PTU in children except in rare instances where methimazole is not tolerated and surgery/radioactive iodine are inappropriate 4, 5, 7