Urinary immunoprecipitation method for estimation of thyroxine to triiodothyronine conversion in altered thyroid states.

A new method is described for the estimation of T4 to T3 conversion in man and is applied to the study of hyperthyroid and hypothyroid clinical states. The method employs simultaneous iv injection of [125I]T4 and [131I]T3 with isolation of the labeled T3 tracers in 4- to 8-day pooled urine samples by a combination of solvent extraction, desalting, and immunoprecipitation procedures. Using [131I]T3 as a recovery standard, the T4 to T3 conversion ratio was found to be 0.470 +/- 0.011 in euthyroid subjects. This confirmed our earlier findings of 0.482 +/- 0.014 using a paper chromatographic method and nonsimultaneous isotope administration. The conversion ratio was increased in hypothyroidism to 0.535 +/- 0.011 (P less than 0.02) and decreased in hyperthyroidism to 0.415 +/- 0.009 (P less than 0.01). These changes parallel the fraction of the radioiodine collected in the urine for both T4 and T3; normal values are 77 +/- 4% for T4 and 76 +/- 4% for T3, values in hypothyroidism are 79 +/- 1% for T4 and 79 +/- 3% for T3, and values in hyperthyroidism are 58 +/- 3% for T4 and 58 +/- 5% for T3 (P less than 0.01). These findings indicate that 1) urinary T4 to T3 conversion values are highly reproducible in euthyroid as well as hyperthyroid and hypothyroid states; 2) the reduction in T4 to T3 conversion in hyperthyroidism probably reflects increased T4 disposal by nondeiodinative pathways and possibly the reverse in hypothyroid states; and 3) since urinary T4 to T3 conversion values in euthyroid subjects exceeded all reported conversion values in blood, there may be an alternate pathway of T3 production and disposal which is not reflected in the blood T3 production rate.

[1]  J. Nicoloff,et al.  A new method for measurement of the conversion ratio of thyroxine to triiodothyronine in euthyroid man. , 1981, The Journal of clinical endocrinology and metabolism.

[2]  S. Ingbar,et al.  The effect of thyroidectomy, hypophysectomy, and hormone replacement on the formation of triiodothyronine from thyroxine in rat liver and kidney. , 1978, Endocrinology.

[3]  M. Kaplan,et al.  Iodothyronine metabolism in liver and kidney homogenates from hyperthyroid and hypothyroid rats. , 1978, Endocrinology.

[4]  P. Larsen,et al.  Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute in , 1978, The Journal of clinical investigation.

[5]  R. Yalow,et al.  Preparation, purification, and stability of high specific activity 125I-labeled thyronines. , 1978, Endocrinology.

[6]  L. Gavin,et al.  Extrathyroidal conversion of thyroxine to 3,3',5'-triiodothyronine (reverse-T3) and to 3,5,3'-triiodothyronine (T3) in humans. , 1977, The Journal of clinical endocrinology and metabolism.

[7]  J. Chambers,et al.  Reduced peripheral conversion of thyroxine to triiodothyronine in patients with hepatic cirrhosis. , 1975, The Journal of clinical investigation.

[8]  K. Torizuka,et al.  Estimation of thyroxine and triiodothyronine distribution and of the conversion rate of thyroxine to triiodothyronine in man. , 1975, The Journal of clinical investigation.

[9]  M. Surks,et al.  Determination of iodothyronine absorption and conversion of L-thyroxine (T 4 ) to L-triiodothyronine (T 3 ) using turnover rate techniques. , 1973, The Journal of clinical investigation.

[10]  E. Newman,et al.  Conversion of Thyroxine to Triiodothyronine in Normal Human Subjects , 1970, Science.

[11]  L. Braverman,et al.  Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects. , 1970, The Journal of clinical investigation.