Determination of iodothyronine absorption and conversion of L-thyroxine (T 4 ) to L-triiodothyronine (T 3 ) using turnover rate techniques.

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).

A new radioimmunoassay for plasma L-triiodothyronine: measurements in thyroid disease and in patients maintained on hormonal replacement.

A new procedure for the radioimmunoassay of l-triiodothyronine (T(3)) in human plasma is described in which the iodothyronines are separated from the plasma proteins before incubation with a specific antiserum to T(3). The antibody bound and free T(3) are separated with dextran-coated charcoal. In this system, the mean recovery of T(3) added to plasma was 97.9% and both in vitro conversion of l-thyroxine (T(4)) to T(3) and cross-reaction between T(4) and the anti-T(3) antibody were undetectable (less than 0.1%). The assay procedure allowed the measurement of T(3) in up to 0.5 ml of plasma resulting in improved assay sensitivity (6 ng/100 ml). The mean plasma T(3) in normal subjects was 146+/-24 ng/100 ml (sd). Mean T(3) concentration was increased in hyperthyroidism (665+/-289 ng/100 ml) and decreased in hypothyroidism (44+/-26 ng/100 ml). In patients with severe hypothyroidism, plasma T(3) was between 7 and 30 ng/100 ml. Plasma T(3) concentration was relatively constant throughout the day in three euthyroid subjects. In contrast, in hypothyroid subjects on replacement therapy with T(3), a T(4): T(3) combination or desiccated thyroid plasma T(3) was markedly elevated for several hours after ingestion of the medication. Plasma T(3) was unchanged throughout the day in patients treated with T(4). Thus, insofar as plasma T(3) levels are concerned, replacement therapy with T(4) appears to mimic the euthyroid state more closely than other preparations.

Specific triiodothyronine binding sites in the anterior pituitary of the rat.

Studies with L-[(125)l] triiodothyronine and L-[(125)l] thyroxine, and with equilibrium dialysis of plasma proteins indicate that rat pituitary binds L-triiodothyronine 9.8 times as strongly as it does L-thyroxine. Injection of even small doses of nonradioactive L-triiodothyronine reduces the pituitary/ plasma ratio of radioactive L-triiodothyronine, an indication of the existence of pituitary binding sites with a limited capacity for L-triiodothyronine. Limited capacity binding sites for L-thyroxine could not be demonstrated.