Thyroid hormone metabolism in amniotic and allantoic fluids of the sheep.

Extract: Amniotic and allantoic fluid samples were obtained at the time of uterotomy from healthy pregnant ewes at various times during gestation. In most instances maternal and fetal blood was collected simultaneously. Serum thyroxine (T4) and triiodithyronine (T3) and free T4 were measured in most samples. To determine whether conjugates of T4 were present in amniotic and allantoic fluids, T4 was measured before and after 24-hr acid hydrolysis. T4 and T3 turnover from amniotic fluid were measured using kinetic methods after intravenous or intraamniotic fluid injection of radiolabeled hormones. T3 was unmeasurable (< 15 ng/100 ml) in amniotic and allantoic fluids as well as in most fetal serum samples. T4 levels in amniotic fluid were low before 120 days of gestation (0.17 ± 0.03 μg/100 ml; mean and SEM) and increased progressively thereafter to term. The mean (and SEM) concentration between 124 and 152 days was 0.33 ± 0.03 μg/100 ml. T4 concentrations in allantoic fluid were relatively high before 120 days (0.57 ± 0.01 μg/100 ml) and did not increase with progression of the pregnancy. There were no correlations between amniotic and allantoic fluid T4 concentrations, between amniotic fluid T4, and either maternal or fetal serum T4 levels, or between allantoic fluid T4 and maternal or fetal serum T4 at any time during gestation. Mean free T4 concentrations were similar in fetal serum and amniotic fluid and higher than values in maternal serum or allantoic fluid. Mean amniotic and allantoic fluid T4 concentrations by radioimmunoassay (RIA) increased significantly after acid hydrolysis, suggesting that one-third to one-half the T4 in these fluids is present as T4 conjugate. Radiolabeled T4 or T3 was injected into amniotic fluid and recovery of hormone label was measured in serum and tissues at 24 hr for comparison with recoveries after intravenous injection. Mean T4 radioactivity in several organs or tissues was nearly identical whether the hormone was injected intravenously or into amniotic fluid. In addition, the total residual labeled T4 or T3 in the fetal sheep (percentage dose per fetus) at the time of killing was similar after intravenous and intra-amniotic fluid injection. Chromatograms of butanol-ammonia extracts of fetal sera after intraamniotic or intravenous injection of labeled T4 were similar and showed predominantly T4; a significant iodide peak was observed as well as a small peak of radioactivity with an RF corresponding to that of T4 conjugate. The results indicate that there are low but measurable concentrations of T4 in amniotic and allantoic fluids of pregnant sheep. There appears to be minimal exchange of hormone between allantoic and amniotic fluid. Amniotic fluid T4 levels, in contrast to allantoic fluid concentrations, increase progressively during the last half of gestation. Although free T4 concentrations are similar in amniotic fluid and in fetal serum, and are higher than in allantoic fluid or maternal serum, the lack of correlation between T4 levels in either fluid and T4 levels in fetal or maternal serum suggests that amniotic or allantoic fluid T4 levels do not reliably reflect thyroid status of the fetus or the mother. Rather, both must be represented in some way. Finally, T4 and T3 appear to be rapidly and quantitatively absorbed from amniotic fluid by the sheep fetus. Speculation: The present results suggest that amniotic fluid T4 is derived both from the mother and the fetus so that measurement of amniotic fluid T4 would not seem to be a reliable approach to intrauterine diagnosis of fetal thyroid status. Amniotic fluid T4 is turned over rapidly by the fetus, presumably via swallowing and absorption from the fetal gut so that the fetus might acquire maternal thyroid hormones via amniotic fluid even though placental transfer of thyroid hormones is minimal. This route of maternal T4 entry to the fetus must be of minimal quantitative significance, however, since the serum T4 concentration in the athyroid sheep fetus is very low. It should be possible, however, to provide thyroid hormone therapy to the fetus via amniotic fluid injection; this approach allows direct intrauterine therapy of fetuses in whom there is a high index of suspicion of hypothyroidism.