Urinary metabolites of 14C-labeled thyroxine in man

Abstract

A B S T R A C T Studies were carried out to determine the chemical structures of thyroxine metabolites after total deiodination. Normal subjects were given thyroxine labeled with "C on the nonphenolic ring and the alanine side chain, 8-11 Ag/day for 10 days. By paper chromatography of fresh urine, six or more "C-labeled compounds were separated. The "C-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 "C-labeled metabolite was identified as thyroacetic acid or 4-phenoxy-(4'-hydroxy) phenylacetic acid. Another one was identified as thyronine. Of the total urinary "C 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 ig/day. The average daily excretion of thyronine was 6.5% of the renal disposal rate of thyroxine or approximately 3.9 ug/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.

Clinical Pharmacokinetics of Hypolipidaemic Drugs

“…Thyroxine is metabolised in man primarily to thyroacetic acid (44 % of the dose) and thyronine (20 % of the dose) with about a fifth of each metabolite being present in urine as glucuronide or sulphate conjugates (Pittman et al, 1972). The average daily rate of the conversion of thyroxine to triiodothyronine was 4 % of the extrathyroidal thyroxine pool (Pittman et al,197 I).…”

Thyroid Hormone and the Kidney

“…Deiodination is the most important metabolic pathway of thyroid hor mones [112,133] [127], considerable evidence attests to the versatility and significance o f the kidney as a major organ in volved in thyroid hormone metabolism. In addition to its ability to carry out all the major degradative pathways mentioned, the kidney also stores more T\i, T3, and inorganic iodide per unit mass than other extrathyroidal tissues [148], and is the most important route for the excretion of inorganic iodide [112].…”

“…In addition to its ability to carry out all the major degradative pathways mentioned, the kidney also stores more T\i, T3, and inorganic iodide per unit mass than other extrathyroidal tissues [148], and is the most important route for the excretion of inorganic iodide [112]. In the first report, C h a n and L a n d o n …”

Histamine mediates behavioural and metabolic effects of 3‐iodothyroacetic acid, an endogenous end product of thyroid hormone metabolism

“…In the presence of deiodinases, TA0 can also be produced. TA1 was recognized as the main oxidative metabolite of T1AM (Wood et al ., ; Saba et al ., ; Agretti et al ., ), while TA0 was identified in human urine as the final end product of thyroid hormone metabolism (Pittman et al ., ). In turn, TA1 can be transformed into T0A, in cells expressing deiodinase activity.…”