What is the preferred treatment between Propylthiouracil (PTU) and Methimazole for hyperthyroidism in the emergent setting?

From the Guidelines

Methimazole is generally the preferred treatment for hyperthyroidism in the emergent setting, except in the first trimester of pregnancy or in cases of severe adverse reactions to methimazole. The choice between Propylthiouracil (PTU) and Methimazole for hyperthyroidism in the emergent setting depends on several factors, including the patient's pregnancy status and the severity of the condition.

• In non-pregnant patients or those beyond the first trimester, methimazole is often preferred due to its more favorable dosing schedule and side effect profile 1.
• However, in the first trimester of pregnancy, PTU is preferred due to the risk of methimazole-associated birth defects 1.
• In cases of thyroid storm, a life-threatening emergency, PTU may be preferred initially at higher doses because it has the additional benefit of blocking peripheral conversion of T4 to T3 1. Key considerations in the emergent setting include:
• The need for rapid control of thyrotoxicosis
• The potential for severe adverse reactions to thionamide medications
• The importance of accompanying treatment with beta-blockers to control sympathetic symptoms
• The potential need for adjunctive therapies such as iodine solutions, glucocorticoids, and cholestyramine in severe cases. It's worth noting that both methimazole and PTU are effective thionamide medications that block thyroid hormone synthesis, but they have different advantages and disadvantages, and the choice between them should be individualized based on the patient's specific situation 1.

From the FDA Drug Label

Because of postmarketing reports of severe liver injury in pediatric patients treated with propylthiouracil, methimazole is the preferred choice when an antithyroid drug is required for a pediatric patient 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. Propylthiouracil is indicated: in patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment option.

In the emergent setting, methimazole is generally the preferred treatment over propylthiouracil (PTU) for hyperthyroidism due to the potential for severe liver injury associated with PTU, especially in pediatric patients 2. However, in pregnant women, particularly during the first trimester, PTU may be considered as an alternative due to the rare occurrence of congenital malformations associated with methimazole use 2. But, given the potential maternal adverse effects of PTU, such as hepatotoxicity, it may be preferable to switch from PTU to methimazole for the second and third trimesters 2. PTU is indicated for patients who are intolerant of methimazole 3.

• Key considerations:
  • Severe liver injury associated with PTU
  • Congenital malformations associated with methimazole use
  • Maternal adverse effects of PTU, such as hepatotoxicity
• Preferred treatment: Methimazole, except in pregnant women during the first trimester, where PTU may be considered as an alternative.

From the Research

Comparison of PTU and Methimazole in Hyperthyroidism Treatment

• The choice between Propylthiouracil (PTU) and Methimazole for treating hyperthyroidism, especially in the emergent setting, depends on several factors including the severity of hyperthyroidism, potential side effects, and the specific characteristics of the patient's condition.
• A study from 2007 4 compared the efficacy and adverse reactions of Methimazole (MMI) and Propylthiouracil (PTU) in patients with hyperthyroidism caused by Graves' disease, suggesting that MMI may be more effective in normalizing serum free T4 (FT4) levels, especially in patients with severe hyperthyroidism.
• However, the same study noted that PTU had a higher incidence of mild hepatotoxicity, which is a significant consideration in the choice of treatment.
• Another study from 1981 5 highlighted the inhibition of peripheral deiodination of T4 to T3 by PTU, which could be beneficial in treating hyperthyroidism but also pointed out potential adverse effects related to this inhibition.
• The risk of hepatotoxicity with both drugs is a critical consideration, as emphasized by a case report from 2018 6 where a patient experienced acute hepatitis with both MMI and PTU, underscoring the need for regular monitoring of liver function.
• Agranulocytosis is another significant side effect associated with both PTU and Methimazole, as discussed in a study from 1977 7, which can be life-threatening and requires immediate attention.
• The comparison of acute changes in T3 and T4 levels during therapy with antithyroid agents, as studied in 1974 8, suggests that PTU and MMI have different effects on T3 production, with PTU causing a more significant decrease in serum T3 levels, potentially due to its inhibition of peripheral T3 production.

Side Effects and Efficacy

• The efficacy of PTU and Methimazole can vary based on the severity of hyperthyroidism and individual patient responses.
• Side effects such as hepatotoxicity and agranulocytosis are critical considerations in the choice between PTU and Methimazole.
• Regular monitoring of liver function and blood cell counts is essential for patients on either medication.

Treatment Choice in the Emergent Setting

• In the emergent setting, the choice between PTU and Methimazole may lean towards Methimazole due to its potentially lower risk of hepatotoxicity and its effectiveness in rapidly reducing thyroid hormone levels, as suggested by some studies 4.
• However, the decision should be tailored to the individual patient's condition, including the severity of hyperthyroidism, presence of any contraindications to either drug, and the ability to monitor for potential side effects closely.