What is the principal mechanism by which this drug act?

A 47-year-old woman presents with complaints of nervousness and increased
sensitivity to hot weather. She is diagnosed with hyperthyroidism and prescribed
propylthiouracil. What is the principal mechanism by which this drug acts?
a) Decreasing the efficacy of TSH binding to the thyroid TSH
receptor
b) Decreasing the rate of proteolysis of thyroglobulin
c) Increasing the amount of 3,3’,5’-triiodothyronine (reverse T3;
rT3)
d) Inhibiting deiodination of thyroxine (T4)
Correct Answer - D
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.