Urinary metabolites of <sup>14</sup>C-labeled thyroxine in man

Constance S. Pittman; Melvin W. Buck; Joseph B. Chambers

doi:10.1172/JCI106977

Urinary metabolites of ¹⁴C-labeled thyroxine in man

Constance S. Pittman, Melvin W. Buck, and Joseph B. Chambers Jr.

Published July 1, 1972 - More info

View PDF

Abstract

Studies were carried out to determine the chemical structures of thyroxine metabolites after total deiodination. Normal subjects were given thyroxine labeled with ¹⁴C on the nonphenolic ring and the alanine side chain, 8-11 μg/day for 10 days. By paper chromatography of fresh urine, six or more ¹⁴C-labeled compounds were separated. The ¹⁴C-labeled metabolites were concentrated by passing the urine through a nonionic polymeric adsorbent. Two major thyroxine metabolites were identified. The identification was made by three different methods: (a) chromatography, (b) synthesis of derivatives, and (c) recrystallization to constant specific activity. One ¹⁴C-labeled metabolite was identified as thyroacetic acid or 4-phenoxy-(4′-hydroxy) phenyl-acetic acid. Another one was identified as thyronine. Of the total urinary ¹⁴C radioactivity, 43.7% was recovered as thyroacetic acid and 19.8% was recovered as thyronine. Approximately one-fifth of each of these metabolites was present in the urine in bound form which released the free metabolites during acid hydrolysis. The average daily excretion of thyroacetic acid was 13.7% of the renal disposal rate of thyroxine, or approximately 7.5 μg/day. The average daily excretion of thyronine was 6.5% of the renal disposal rate of thyroxine or approximately 3.9 μg/day while the urinary iodide made up 64.7% of the renal disposal rate of thyroxine. Our findings provide the needed proof that the major metabolic pathways of thyroxine remove the iodine atoms by substituting hydrogen for iodine and leave the diphenyl ether nucleus intact.