From the Guidelines
Propylthiouracil (PTU) works by inhibiting the synthesis of thyroid hormones in the thyroid gland, specifically blocking the enzyme thyroid peroxidase, and also inhibiting the peripheral conversion of T4 to T3 by blocking the enzyme 5'-deiodinase. This dual mechanism of action makes PTU a useful medication for treating hyperthyroidism, including in pregnant women, as noted in the American College of Obstetricians and Gynecologists (ACOG) practice bulletin on thyroid disease in pregnancy 1. The goal of treatment with PTU is to maintain FT4 or FTI in the high-normal range using the lowest possible dosage, with monitoring of FT4 or FTI every two to four weeks to adjust the dose as needed.
Some key points to consider when using PTU include:
- The medication is typically dosed at 100-150 mg orally three times daily initially for hyperthyroidism, with maintenance doses of 50-150 mg daily once euthyroid state is achieved
- PTU is preferred over methimazole during the first trimester of pregnancy due to lower risk of birth defects, though it carries a higher risk of hepatotoxicity, as noted in the ACOG practice bulletin 1
- Patients should be monitored for side effects including rash, arthralgias, and the rare but serious complications of agranulocytosis and liver failure, with discontinuation of the medication and further evaluation if symptoms such as sore throat and fever develop 1
- Full therapeutic effect may take 4-8 weeks as the medication does not affect already formed thyroid hormones circulating in the bloodstream.
From the FDA Drug Label
CLINICAL PHARMACOLOGY: Propylthiouracil inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. The mechanism of action (MOA) of prophylthiouracil is:
- Inhibition of thyroid hormone synthesis
- Inhibition of the conversion of thyroxine to triiodothyronine in peripheral tissues 2
From the Research
Mechanism of Action of Propylthiouracil
- Propylthiouracil (PTU) is a thiourea-based compound that inhibits thyroid hormone biosynthesis and decreases the conversion of T4 to T3 3.
- PTU irreversibly inhibits thyroid peroxidase (TPO), a heme enzyme that uses iodide and hydrogen peroxide to perform iodination and phenolic coupling reactions 3.
- PTU also inhibits type 1 deiodinase (ID-1), which is involved in the conversion of T4 to T3, by reacting with the selenenyl iodide intermediate 3.
- The presence of the -N(H)-C(═O)- functionality in PTU allows it to form hydrogen bonds with nearby amino acid residues in the selenenyl sulfide state, contributing to its ID-1 inhibitory activity 3.
Clinical Use of Propylthiouracil
- PTU is used to treat hyperthyroidism, particularly in patients with Graves' disease 4, 5.
- Combination therapy with PTU and cholestyramine has been shown to be effective in reducing thyroid hormone levels in patients with Graves' hyperthyroidism 5.
- PTU has also been shown to have antioxidant properties, reducing lipid peroxidation and increasing antioxidant status in hyperthyroid patients 6.