Establishment of the sulfated 3,3'-diiodothyronine radioimmunoassay and its application in pregnant women.

: Sulfation of iodothyronines is a major alternate pathway of thyroid hormone metabolism during fetal development. Sulfated 3,3'-diiodothyronine (T2S) is a low end metabolite of this pathway. Its clinical implications in the prenatal evaluation of fetal thyroid disorders are now being intensively investigated. A highly sensitive and reproducible radioimmunoassay (RIA) for T2S has been established in our laboratory. The detection threshold of the RIA approximated 5 pg T2S. The dose-response curve of T2S was essentially linear between 5-200 pg. An essentially parallel correlation of the dose-response curves for inhibition of binding of radiolabeled T2S and T2S antiserum was found between serial dilutions of serum extracts and the standards. The average intra- and inter-assay coefficients of variation were 7% and 15%, respectively. By applying the T2S RIA, we found that serum titers of T2S in pregnant women increased proportionately to the gestational age (first trimester vs. second trimester vs. third trimester: 30.1 +/- 1.4 vs. 41.6 +/- 1.9 vs. 98.0 +/- 3.9 ng/dL; p < 0.001 each). A high concentration of T2S was detected in cord and maternal serum at birth as compared to the results for non-pregnant women (165.1 +/- 10.3 vs. 113.7 +/- 5.6 vs. 7.5 +/- 0.9 ng/dL). The T2S levels decreased remarkably in maternal circulation 10 days after partuition. Four pregnant women who had two blood samplings four or more weeks apart during the third trimester showed invariable increases of serum T2S titers at later sampling times. Additionally, in the case of a pregnant woman who received two doses of T4 injections (200 micrograms/wk) intraamniotically for a previous Cretin birth, the maternal serum levels of T2S increased promptly from 47 ng/dL [corrected] to 96 ng/dL. Our findings imply that the established T2S RIA is clinically applicable, provide further evidence that the coincident increase of serum T2S titers in pregnant women may reflect ontogenesis of fetal thyroid hormone maturation, and provide a clue to the fetal thyroid status in the prenatal stage. However, more knowledge is still needed regarding the transfer and transformation of sulfated iodothyronine(s) from the fetal compartment to maternal circulation.