Peripheral Metabolism of Thyroid Hormones in Man, I. Direct Measurement of the Conversion Rate of Thyroxine to 3,5,3'-Triiodothyronine (T₃) and Determination of the Peripheral and Thyroidal Production of T₃

Abstract

We describe here a new method for the direct measurement of the conversion rate of T4 to T3 in man. The metabolic study was performed in 23 subjects: 13 healthy controls, 7 T4-treated hypothyroids, and 3 sick euthyroid patients. The experimental protocol involved the simultaneous iv bolus injection of [125I]T4 and [131I]T3, and the use of Sephadex G-25 column chromatography to determine the plasma concentrations of [125I]T4, [131I]T3, and [125I]T3 newly formed through 5'-monodeiodination of labeled T4 in the peripheral tissues. The T4 and T3 kinetic parameters were determined by noncompartmental analysis. The conversion rate of T4 to T3 was computed by a method based on the precursor-product relationship, using the [131I]T3 disappearance curve for correcting the concentrations of newly formed [125I]T3 (convolution method). The conversion rate of T4 to T3 was 0.2541 +/- 0.0125 (mean +/- SEM) in the control group and was significantly reduced (0.1283 +/- 0.0204; P less than 0.001) in the sick euthyroid patients, while it was slightly, though not significantly, increased in the T4-treated patients (0.2932 +/- 0.0220). A close agreement was found between the values for the conversion rate obtained by the convolution approach and those derived from the ratio between the serum concentrations of [125I]T3 and [125I]T4 at equilibrium. The conversion rates obtained by the convolution approach were also in good agreement with the values estimated from the molar ratio between the turnover rates of T3 and T4. In the control group, 72.0 +/- 3.6% of the circulating T3 was produced by 5'-monodeiodination of T4 in the peripheral tissues, and 28.0 +/- 3.6% of the circulating T3 derived from direct thyroidal secretion. The sick euthyroid patients showed a significantly smaller proportion of circulating T3 deriving from peripheral conversion of T4 (52.5 +/- 3.9%; P less than 0.025).

Seasonal influence on thyroidal response to thyrotrophin-releasing hormone in cattle and buffaloes

“…In man about 70% of circulating T3 is derived from peripheral monodeiodination of T4 (Bianchi, Mariani, Molea et al 1983). In some species, during hot climatic condi¬ tions, peripheral monodeiodination of T4 has been shown to be suppressed (Pathak & Chandola, 1982).…”

Role of serum carrier proteins in the peripheral metabolism and tissue distribution of thyroid hormones in familial dysalbuminemic hyperthyroxinemia and congenital elevation of thyroxine-binding globulin.

“…The consensual change oftotal serum T4 concentration and overall T4 to T3 conversion (n = 7, r = 0.70) in FDH subjects is at variance with the inverse correlation between these parameters reported by other authors and by us in subjects without alteration of thyroid hormones serum carrier proteins (12,41,42). However, the overall T4 to T3 conversion ratio appears to bear a closer relationship to T4 PR than to serum T4 concentration.…”

“…Venous blood samples were taken at frequent intervals for the first 24 h (0.08, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 18, 24 h), then every 12, 24 h until 144-192 h after injection, and the plasma disappearance curves of 125I-T4 and '3'1-T3 and concentrations of '25I-T3 newly formed from 5'-monodeiodination of tracer '25I-T4 were determined by a chromatographic system using Sephadex G-25 (Superfine, Pharmacia, Uppsala, Sweden) as previously described (12). This method allows quantitative recovery and complete separation of labeled T4 and T3 from their labeled metabolites.…”

“…The plasma appearance curve of 1251-T3 generated in vivo from the injected 125I-T4 was used to estimate the 14 to T3 conversion ratio (CR) using a convolution approach previously described (12,25,26). The peripheral production rate of T3 was then obtained as the product of the T4 production rate by the T4 to T3 CR (after correction for the T3/=4 molecular weight ratio); the thyroidal T3 secretion rate (T3 SR) was obtained as the difference between the total T3 production rate (T3 PR) and the peripheral T3 production rate.…”

Thyroid Function Testing

“…Most methods use radiolabeled iodothyronine tracers injected intravenously. 231,233,234 Their disappearance is monitored in serum samples obtained at various intervals after injection of the tracers by means of chromatographic and immunologic techniques of separation. Kinetic parameters can be calculated by noncompartmental analysis or by two-or multiple-compartment analysis.…”