Determination of Iodothyronine Absorption and Conversion of L-Thyroxine (T4) to L-Triiodothyronine (T3) using Turnover Rate Techniques

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Abstract
The absorption of L-thyroxine (T4) and L-triiodothyronine (T3) and the fractional rate of conversion of T4 to T3 were determined from the turnover rates of T4 and T3 in seven patients without endogenous thyroid function during separate treatment periods with these iodothyronines. Serum T3 concentration was measured by a radioimmunoassay procedure in which the iodothyronines are separated from the plasma proteins before incubation with anti-T3 antibody. Metabolic clearance rates were calculated by an integral (noncompartmental) approach since the use of single compartment kinetics led to a 40% overestimation of the metabolic clearance rate of T3. Based on the amount of hormone ingested and the observed hormonal turnover rates, the absorption of T4 and T3 (iodothyronine turnover/iodothyronine ingested) in man could be estimated. Absorption of T3 was complete in three subjects but decreased to 43% in a fourth who was suffering from mild congestive heart failure. Mean T4 absorption was 48.0±2.6% (SEM) for seven subjects. The mean fractional rate of T4 to T3 conversion determined during T4 replacement therapy (T3 turnover/T4 turnover) was 42.6% (range 30.7-50.8%). Thus, approximately one-half of the T4 which was deiodinated was converted to T3 suggesting that monodeiodination is an obligatory step in the peripheral metabolism of T4. Calculations based on these results together with other available data suggest that under normal physiologic circumstances the major portion of the T3 pool is derived from monodeiodination of T4.