What is the preferred treatment between Propylthiouracil (PTU) and Medamidoxole for a patient with hyperthyroidism, particularly those with Graves' disease, considering pregnancy status and potential contraindications?

PTU vs Methimazole for Hyperthyroidism

For non-pregnant patients with Graves' disease, methimazole is the preferred first-line antithyroid drug due to superior safety profile, once-daily dosing, and lower cost, while propylthiouracil (PTU) should be reserved for first trimester pregnancy or methimazole intolerance. 1

Treatment Selection Algorithm

For Non-Pregnant Adults

• Methimazole is the drug of choice for initial treatment of Graves' hyperthyroidism 1
• Starting dose: 10-30 mg once daily 2
• Methimazole has fewer major side effects compared to PTU and allows convenient single daily dosing 2
• PTU requires dosing every 6 hours (100-300 mg per dose), making adherence more challenging 2

Critical caveat: PTU carries a black box warning for severe hepatotoxicity, including hepatic failure requiring liver transplantation or resulting in death 3. This risk is particularly concerning in the pediatric population, where PTU is not recommended except when methimazole is not tolerated and ablative therapies are inappropriate 3.

For Pregnant Women

First Trimester (Weeks 0-13):

• PTU is the preferred agent due to lower risk of congenital abnormalities compared to methimazole 4
• Methimazole has been associated with specific teratogenic effects including aplasia cutis and choanal/esophageal atresia 2, 5
• Women on methimazole who are planning pregnancy should be switched to PTU 1

Second and Third Trimesters (Weeks 14-40):

• Switch from PTU to methimazole is preferable given the potential for maternal hepatotoxicity from PTU 3
• The American Academy of Family Physicians recommends methimazole as preferred during second and third trimesters 4
• This trimester-specific approach balances fetal teratogenic risk (higher with methimazole in first trimester) against maternal hepatotoxic risk (higher with PTU throughout pregnancy) 5

Monitoring Requirements

Thyroid Function

• Monitor free T4 or free thyroxine index (FTI) every 2-4 weeks initially to adjust dosage 4
• Goal: maintain free T4 in the high-normal range using the lowest possible dose 4
• Check TSH every trimester once stable 4

Safety Monitoring

• For PTU: Monitor for signs of hepatotoxicity (tiredness, nausea, anorexia, fever) and vasculitis (new rash, hematuria, decreased urine output, dyspnea, hemoptysis) 3
• For both drugs: Monitor for agranulocytosis (sore throat, fever) - patients should discontinue immediately and contact physician if these symptoms develop 4, 3
• Consider monitoring prothrombin time, especially before surgical procedures, as PTU may cause hypoprothrombinemia 3

Special Clinical Scenarios

High TRAb Levels in Pregnancy

• Patients with elevated thyrotropin receptor antibodies (TRAb) require continued antithyroid treatment throughout pregnancy to prevent fetal and neonatal thyrotoxicosis, regardless of maternal euthyroid status 6
• Maternal TRAb crosses the placenta and can stimulate fetal thyroid 6
• Inform the newborn's physician about maternal Graves' disease due to risk of neonatal thyroid dysfunction 4, 6

Thyroid Storm

• Medical emergency requiring immediate treatment without waiting for laboratory confirmation 4
• Treatment includes PTU or methimazole, potassium/sodium iodide solutions, dexamethasone, phenobarbital, and supportive care 4
• Avoid delivery during thyroid storm unless absolutely necessary 4

Common Pitfalls to Avoid

• Do not use radioactive iodine (I-131) during pregnancy - it is absolutely contraindicated as it causes fetal thyroid ablation 4
• Do not continue PTU throughout entire pregnancy when methimazole is a safer option for second and third trimesters 3
• Do not use PTU in children except in rare instances when methimazole is not tolerated and ablative therapies are inappropriate 3
• Do not undertreated hyperthyroidism in pregnancy - this increases risks of preeclampsia, preterm delivery, heart failure, miscarriage, low birth weight, and fetal thyroid dysfunction 4

Duration of Treatment

• Standard course: 12-18 months for adults 1, 7
• Children: 24-36 months recommended 1
• Approximately 50% of patients relapse after completing antithyroid drug therapy, at which point definitive treatment (radioactive iodine or thyroidectomy) should be offered 7