Effect of 5- and 6-Propylthiouracil on the Metabolism of L-Thyroxine in Man

The effect of 5-propylthiouracil (5-PTU) and 6-propylthiouracil (6-PTU) on the metabolism of thyroxine was studied in 10 euthyroid patients. After a single dose of I131-labeled L-thyroxine given intravenously, radioactivity in the serum, urine and stool was measured daily. Potassium perchlorate was given throughout the study to block recycling of iodide by the thyroid. After an 8- to 9-day control period, either 5-PTU (400 mg daily) or 6-PTU (400–800 mg daily) was given for 8 days. 5-PTU reduced urinary I131 30–44 % and increased fecal I131 in all patients. 6-PTU reduced urinary I131 only 0–11 % and increased fecal I131 in only 1 patient. Decay in serum was slowed significantly in 2 patients given 5-PTU. In 5 patients the serum decay curve during treatment was slightly elevated above the extrapolated control decay curve, but the slope was unchanged. Serum protein-bound iodine (PBI) was increased 1.2±0.4 μg/100 ml in 7 patients. In 2 of 3 patients, counting over the liver indicated increased concentration of radioactivity during treatment. The study showed that in man 5-PTU was a more potent inhibitor of the deiodination of thyroxine than was 6-PTU. The inhibition of deiodination was accompanied by increased concentration of radioactivity in the liver and increased fecal radioactivity, a slight rise in protein-bound iodine, and occasional slowing of degradation in serum.