Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects

Abstract

A B S T R A C T Studies of the possibility that thyroxine (T4) is converted to 3,5,3'-triiodo-L-thyronine (T3) in the extrathyroidal tissues in man have been conducted in 13 patients, all but two of whom were athyreotic or hypothyroid, and all of whom were receiving at least physiological replacement doses of synthetic sodium-Lthyroxine.T3 was found in the sera of all patients, in concentrations ranging between 243 and 680 ng/100 ml (normal range 170-270 ng/100 ml). These concentrations were far in excess of those which would have been expected on the basis of the T3 contamination of the administered T4, as measured by the same technique employed in the analysis of serum. When oral medication was enriched with 'I-labeled T4 for 8 or more days, labeled T3 and tetraiodothyroacetic acid (Tetrac or TA4) were found in the serum to the extent of approximately 2-5% of total radioactivity, as assessed by unidimensional paper chromatography. The same results were obtained with a specially purified lot of radioactive T4 containing less than 0.1% T3 as a contaminant. The identities of the 'I-labeled T3 and TA4 were verified by two-dimensional chromatography as well as by specific patterns of binding in serum. The labeled T3 isolated was bound by albumin and by T4-binding globulin (TBG), but not by T4-binding prealbumin (TBPA); in contrast the labeled TA4 was bound by albumin and TBPA, but not by TBG.To exclude the possibility that the conversion of T4 to T3 was a peculiarity of the oral route of administra- There is no doubt whatsoever that at least a portion of the T3 in the blood results from direct secretion by the thyroid gland, T3 having been found in the thyroid venous effluent, and in concentrations substantially higher than in the concurrently sampled arterial blood (4, 5). What has remained uncertain, however, is what fraction, if any, of the T3 in the blood arises from the

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

“…Several previous studies suggest that about 85% of T4 produced daily is metabolized by deiodination (26,(30)(31)(32)(33); the rest is apparently lost as T4 or its conjugates (32) or is metabolized by deamination and decarboxylation of alanine side chain to tetraiodothyroacetic acid (34). It has also been demonstrated that deiodination of T4 can occur both in the phenolic and in the tyrosyl ring of the T4 molecule (1,35).…”

“…Thus (34), it seems possible that in addition to the above-mentioned abnormalities in T4 metabolism, the pathway of conversion of T4 to tetraiodothyroacetic acid or another side chain derivative of T4 may be accelerated in a systemic illness such as hepatic cirrhosis.…”

“…It seems possible, however, that the apparent shunting of T4 from conversion to highly potent T3 (39) to the production of calorigenically inactive rT3 (40,41) or other metabolites of T4 such as tetraiodothyroacetic acid (34,42) may reflect a defense reaction of the body intended to safeguard against excessive metabolic stimulation during illness. Obviously, much further study will be needed before this or an alternative possibility can be established.…”

“…The Journal of Clinical Investigation Volume 58 July 1976- [32][33][34][35][36][37][38][39][40] turnover rate of reverse T3. Similarly, little information is available regarding the relative significance of the contribution of the thyroidal secretion and the peripheral metabolism of T4 to serum rTa in man.…”

Thyroid hormone action in metabolic regulation

“…The biologically active form of thyroid hormone is T3, whereas T4 is the most abundant thyroid hormone in the blood. In target tissues, type I or type II 5'-deiodinase (DI or DII) catalyzes the deiodination of T4 and controls the local T3 concentration in cells (Braverman et al, 1970;Köhrle, 2000).…”