From the Guidelines
Propylthiouracil works by inhibiting the synthesis of thyroid hormones in the thyroid gland, primarily through the inhibition of thyroid peroxidase, and also by blocking the peripheral conversion of T4 to T3. The medication's mechanism of action involves blocking the enzyme thyroid peroxidase, which is crucial for incorporating iodine into thyroglobulin, a key step in thyroid hormone production 1. This inhibition prevents the iodination of tyrosine residues and the coupling of iodotyrosines, effectively reducing the formation of the active thyroid hormones thyroxine (T4) and triiodothyronine (T3). Some key points to consider when using propylthiouracil include:
- The goal of treatment is to maintain FT4 or FTI in the high-normal range using the lowest possible thioamide dosage 1
- Measuring the FT4 or FTI every two to four weeks can be helpful in adjusting the dosage 1
- Potential side effects of propylthiouracil include agranulocytosis, hepatitis, vasculitis, and thrombocytopenia, and patients should be monitored for these conditions 1
- Propylthiouracil is preferred over methimazole during the first trimester of pregnancy due to a lower risk of specific birth defects, although it carries a higher risk of liver injury than other antithyroid drugs.
From the FDA Drug Label
Propylthiouracil inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. The drug does not inactivate existing thyroxine and triiodothyronine that are stored in the thyroid or circulating in the blood, nor does it interfere with the effectiveness of thyroid hormones given by mouth or by injection. Propylthiouracil inhibits the conversion of thyroxine to triiodothyronine in peripheral tissues and may therefore be an effective treatment for thyroid storm.
The mechanism of action (MOA) of propylthiouracil 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
The mechanism of action of propylthiouracil (PTU) involves several key aspects:
- Inhibition of thyroid peroxidase (TPO): PTU inhibits the TPO-catalyzed oxidation and iodination reactions, which are essential for thyroid hormone synthesis 3.
- Inhibition of selenocysteine-containing enzyme ID-1: PTU reacts with the selenenyl iodide intermediate (E-SeI) to inhibit the ID-1 enzyme 3.
- Blockage of extrathyroidal conversion of thyroxine to triiodothyronine: PTU inhibits the peripheral deiodination of thyroxine (T4) and triiodothyronine (T3), decreasing the metabolic effectiveness of T4 4.
- Preferential inhibition of thyroxine and 3,5,3'-triiodothyronine formation: PTU has a specific inhibitory effect on the coupling reaction, independent of its inhibitory effect on peroxidase-catalyzed iodination 5.
Clinical Implications
The clinical implications of PTU's mechanism of action include:
- Effective treatment of Graves' disease: PTU is a valuable thyrostatic drug for the treatment of thyrotoxic patients with Graves' disease 6.
- Alternative to methimazole: PTU can be used as an alternative to methimazole, especially for thyrotoxic nursing mothers and patients who experience side effects with methimazole 6.
- Recommended for pregnant women: PTU is recommended for the treatment of thyrotoxicosis in pregnant women due to its comparatively little placental transfer 6.