Maternal compound W serial measurements for the management of fetal hypothyroidsm

Objective: The diagnosis of fetal hypothyroidism is based at present on mea surements of TSU and free thyrosine (FT-1) in fetal blood samples obtained by cordocentesis. The measurement of maternal serum and urinary concentrati ons of compound W, immunologically similar to but chromatograpically distin ct from diiodothyronine sulfate (T2S), has been advocated as a new possible marker for fetal hypothyroidism. Design: In this paper, we measured serum compound W levels in 84 pregnant w omen, 20 with and 64 without thyroid disorders before and during specific t reatment. Compound W was also assessed in fetal blood obtained by cordocent esis from 49 normal fetuses and 4 fetuses with suspected hypothyroidism due to transplacental passage of propylthiouracil (PTU). Compound W levels wer e measured by T2S RIA in maternal and fetal serum. To assess the possible u sefulness of 3,5,3'-triiodothyroacetic acid (TRIAC) for therapy of fetal hy pothyroidism we evaluated the transplacental passage of TRIAC by administer ing the drug to four pregnant women before therapeutic abortion. Results: In normal pregnancies, both maternal and fetal compound W levels i ncreased progressively during gestation with a significant direct correlati on (P <0.001, in both mothers and fetuses). Moreover, a significant positiv e correlation was observed between fetal compound W and fetal FT4 values (P <0.005), whereas no correlation was observed between maternal serum compou nd W and maternal FT4 in either euthyroid or hyperthyroid women, suggesting the fetal origin of compound W. The hypothyroid fetuses of PTU-treated mot hers showed low compound W levels, and maternal compound W values were in t he low normal range and did not show the typical increase during progressio n of gestation. A significant increase of maternal compound W was observed when the PTU dose was reduced. TRIAC was documented to cross the placental barrier and the treatment of a hyperthyroid pregnant woman on PTU caused th e high fetal TSH levels and goiter to normalize. Conclusions: Serial measurements of 3,3'-T2S crossreactive materials (compo und W and 3,3'-diiodothyroacetic acid sulfate) in maternal blood and the ad ministration of TRIAC to the mother may represent a useful and safe alterna tive to invasive techniques for the diagnosis and therapy of fetal hypothyr oidism.