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THE DIFFERENCE IN THYROID HORMONE METABOLISM BETWEEN MAMMALIAN FETUSES AND ADULTS AND ITS IMPLICATIONS
Sing-Yung Wu, M.D., Ph.D.
The neonatal screening program for congenital hypothyroidism (CH) implemented nearly half a century ago has helped a lot of neonates with CH. However, judging from the early involvement of thyroid hormone (TH) in brain development, the reliance on the neonatal strategy to reverse 'ALL' of the cerebral and other developmental anomalies may be in question, and there is room for improvement. The study from our group in the past three decades has demonstrated that sulfo-conjugation is the primary pathway for TH metabolism in developing fetuses in utero that is distinctly different from adults. Our studies have also shown that 3,3'-diiodothyronine sulfate (3, 3'-T2S) is a major fetal metabolite in inactivating TH in the developing mammals that do not need the active catabolic hormones. Further, 3, 3'-T2S has been shown to cross the placenta and return to the maternal circulation. The appearance of W-compound, a material detected by3, 3'-T2S-specific antibody in human maternal and fetal circulation has been shown to correlate significantly to fetal thyroid function. It is time to consider a different approach by taking advantage of the difference in TH metabolism between fetuses and adults. Further study on the sulfation pathway may provide an alternative strategy to the current neonatal screening and the "catch-up" therapy after birth.[Full Text Article]