A 47-year-old woman presents with complaints of nervousness and increased sensitivity to hot weather. She is diagnosed with hypehyroidism and prescribed propylthiouracil. What is the principal mechanism by which this drug acts?
Propylthiouracil works primarily by inhibiting the peripheral conversion of T4 to T3. The thyroid extracts iodide from the plasma and, in an oxidative process, iodinated tyrosine residues in thyroglobulin molecules. Monoiodotyrosine and diiodotyrosine are formed and then coupled to produce either thyroxine (tetraiodothyronine, T4) or triiodothyronine (T3). Proteolytic cleavage of thyroglobulin molecules leads to free T3 or T4, which is then released into the circulation; T3 is several times more potent than T4. Peripheral deiodination of T4 at the 5&; position leads to T3 formation (mainly in the liver); this step is inhibited by propylthiouracil. Decreasing the efficacy of TSH binding, decreasing the rate of thyroglobulin proteolysis, increasing the amount of rT3 formation, and inhibiting the uptake of iodide into the thyroid, would all tend to decrease the formation of thyroid hormones in the thyroid itself. Ref : K.D TRIPATHI 8th ed
Decreasing the efficacy of TSH binding to the thyroid TSH receptor
Decreasing the rate of proteolysis of thyroglobulin
Increasing the amount of 3,3',5'-triiodothyronine (reverse T3; rT3)
Inhibiting deiodination of thyroxine (T4)
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