What is the difference between Propylthiouracil (PTU) and Carbimazole in treating hyperthyroidism?

Differences Between Propylthiouracil (PTU) and Carbimazole in Treating Hyperthyroidism

Propylthiouracil (PTU) should be used in the first trimester of pregnancy, while carbimazole/methimazole is preferred in non-pregnant patients and after the first trimester due to their different side effect profiles and efficacy. 1, 2

Mechanism of Action

• Both drugs: Thionamides that inhibit thyroid hormone synthesis
• PTU: Additionally blocks peripheral conversion of T4 to T3
• Carbimazole: Rapidly metabolized to methimazole (its active form) after absorption 3

Efficacy

• Carbimazole/Methimazole:

  • More potent on a milligram basis
  • Longer half-life allowing once-daily dosing
  • Better compliance due to less frequent dosing 4

• PTU:

  • Shorter half-life requiring multiple daily doses
  • Typically dosed 3 times daily 2

Side Effect Profiles

Carbimazole/Methimazole:

• Teratogenic risk: Higher risk of congenital malformations (aplasia cutis congenita) when used in first trimester 3, 5
• Hepatotoxicity: Lower risk of severe liver injury compared to PTU 6
• Dosing convenience: Once-daily dosing due to longer half-life 2

Propylthiouracil (PTU):

• Teratogenic risk: Lower risk of birth defects in first trimester compared to carbimazole/methimazole 6
• Hepatotoxicity: Higher risk of severe liver injury, especially in children and adolescents 3, 6
  • Odds of liver function injury 2.4 times higher than with methimazole 6
  • Odds of elevated transaminases nearly 4 times higher than with methimazole 6

Common Side Effects for Both:

• Agranulocytosis (rare but serious, typically within first 3 months)
• Rash and urticaria
• Arthralgias (1-5% of patients)
• Dose-dependent hypothyroidism 3

Clinical Applications

Pregnancy:

• First trimester: PTU preferred due to lower teratogenic risk 2, 5
• Second and third trimesters: Switch to carbimazole/methimazole due to lower hepatotoxicity risk 2

Non-pregnant adults:

• Carbimazole/methimazole is generally preferred due to:
  • Once-daily dosing
  • Lower hepatotoxicity risk
  • Similar efficacy 4

Children and adolescents:

• Historically PTU was used, but current recommendations favor carbimazole/methimazole due to PTU's higher risk of severe hepatotoxicity in this population 3

Breastfeeding:

• Both drugs are considered compatible with breastfeeding 2, 3

Monitoring

• Both drugs: Monitor thyroid function every 2-4 weeks initially, then every 3-6 months once stable 2
• Target: Maintain free T4 or Free T4 Index in the high-normal range using lowest possible dose 2
• Side effect monitoring: Watch for symptoms of agranulocytosis (sore throat, fever) and hepatotoxicity (abdominal pain, jaundice) 1, 2

Important Considerations

• Switching between carbimazole and methimazole is not recommended for side effects as carbimazole is metabolized to methimazole 3
• Cross-reactions between thioimidazoles (carbimazole/methimazole) and PTU can occur with some side effects 3
• For patients with Graves' disease, treatment duration is typically 12-18 months 7