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

Abstract

The absorption of L-thyroxine (T(4)) and L-triiodothyronine (T(3)) and the fractional rate of conversion of T(4) to T(3) were determined from the turnover rates of T(4) and T(3) in seven patients without endogenous thyroid function during separate treatment periods with these iodothyronines. Serum T(3) concentration was measured by a radioimmunoassay procedure in which the iodothyronines are separated from the plasma proteins before incubation with anti-T(3) 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 T(3). Based on the amount of hormone ingested and the observed hormonal turnover rates, the absorption of T(4) and T(3) (iodothyronine turnover/iodothyronine ingested) in man could be estimated. Absorption of T(3) was complete in three subjects but decreased to 43% in a fourth who was suffering from mild congestive heart failure. Mean T(4) absorption was 48.0+/-2.6% (SEM) for seven subjects. The mean fractional rate of T(4) to T(3) conversion determined during T(4) replacement therapy (T(3) turnover/T(4) turnover) was 42.6% (range 30.7-50.8%). Thus, approximately one-half of the T(4) which was deiodinated was converted to T(3) suggesting that monodeiodination is an obligatory step in the peripheral metabolism of T(4). Calculations based on these results together with other available data suggest that under normal physiologic circumstances the major portion of the T(3) pool is derived from monodeiodination of T(4).