Metabolism of131I- and14C-Labeled Thyroxines

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Abstract
Thyro-xine metabolism was studied with 4 radiothyroxines labeled as follows: 1) with I131 at 3[image] , 5[image] positions 2) with C14 in the beta carbon of the alanine side chain, 3) with C14 in the alanine side chain and ring A, and 4)wlth C14 in ring B. The study was made in thyroidectomized rats, maintained in a euthyroid state by a daily injection of thyroxine (T4), 15 [mu]/kg- At the start of an experiment, the replacement therapy was substituted with the injection of a radiothyroxine. Their biological t 1/2, urinary and fecal excretion, and the metabolites in blood, bile, urine and feces of these radiothyraxies were compared. The latter 2 radiothyraxines had t1/2s of 28.9 and 20.8 hr, while the first 2 radiothy-roxines showed similart1/2s of 16.6 hr. The total recovery of radioactivity over 10 days was 70-90% in all experiments, approximately 3/4 of which was recovered in the feces. The urinary recovery varied between groups: more I131 than Ci4 was recovered and the least C14 was recovered from the ring B-labeled T4. In the blood, only T4 and iodide were present in detectable amounts. T4 was present mainly as T4 glucuronide in the bile and was excreted along with trace amounts of iodide and several unidentified T4 metabolites, some of which had no 3[image] , 5[image] -iodine. Free Ta and a trace of tetraiodothyroacetic acid were recovered in the feces. In the urine, iodide and 3 unidentified metabolites were observed. These urinary C14-metabolites were deiodinated in 3[image] , 5[image] positions but still kept an intact diphenyl ether structure. The data suggest that in the rat the bulk of T4 is degraded without rupturing the diphenyl ether linkage.