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The Effect of Fetal Thyroidectomy on Thyroid Hormone Metabolism in Maternal and Fetal Sheep

Extract: Experiments were conducted to assess the changes in fetal and maternal iodothyronine kinetics in sheep after removal of the fetal thyroid gland early in the 3rd trimester. Uterotomy was performed at 90–125 days of gestational age; the fetal neck was isolated and a thyroidectomy performed. Indwelling exteriorized fetal carotid artery and maternal jugular vein catheters were inserted and dual 131I- and 125I-labeled iodothyronine kinetic studies were conducted in the mother and fetus, respectively, at 4–37 days post-thyroidectomy. Serum thyroxine (T4), triodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay (RIA). Before thyroidectomy the mean fetal serum T4 level was 12.2 μg/100 ml (nine animals); this value fell to a mean of 1.7 μg/100 ml 3 days postoperatively and to a mean of <0.7 μg/100 ml 5–6 days post-thyroidectomy. The mean fetal serum T3 level was <18 ng/100 ml before thyroidectomy and remained unmeasurable throughout the study. The mean maternal serum T4 and T3 concentrations were 8.9 μg/100 ml and 94 ng/100 ml before thyroidectomy and did not change significantly during the study period. Maternal T4 turnover (T4s) averaged 533 μg/24 hr (11.9 μg/kg/24 hr) after fetal thyroidectomy, whereas the fetal value was <4.9 μg/24 hr (<3.2 μkg/24 hr). Maternal T3 turnover (T3s) averaged 62 μg/24 hr (1.27 μg/24 hr) after fetal thyroidectomy; the fetal value was <2.26 μg/24 hr (<1.05 μg/kg/24 hr). These fetal values, and particularly the the T4 results, are much less than those in the euthyroid fetus ( < 1.45 and 41 μg/kg/24 hrfor T3 and T4).Placental transfer of butanol-extractable T4 and T3 radioactivity occurred in both the fetal-maternal (F-M) and maternal-fetal (M-F) directions; chromatographic studies revealed that the transferred radioactivity represented T4 or T3. The mean fractional rate constants for T4 transfer were 0.0009/hr−1 and 0.00003/hr−1 and for T3 transfer, 0.007/hr−1 and 0.002/hr−1 in the F-M and M-F directions. Estimated net transfer of T4 was 0.6 μg and of T3, 0.7 μg/24 hr in the M-F direction. These amounts represent only about 7% of total T4 equivalent turnover (T4s + 4 × T3s) in euthyroid fetuses, and the high fetal serum TSH concentrations (300–1,500 μU/ml) indicated that the thyroidectomized fetuses were, in fact, hypothyroid. The present data indicate that fetal thyroidectomy in the sheep results in fetal hypothyroidism which persists in spite of large M-F gradients of T4 and T3 and a large F-M gradient of TSH. The results further substantiate the autonomy of the fetal pituitary-thyroid system; TSH and thyroid hormones do not cross the placenta in significant quantities even after fetal thyroidectomy.Speculation: The present results suggest that the athyroid fetus probably develops in utero in the absence of significant quanities of thyroid hormones. The fact that growth retardation is not observed at birth in the athyroid human fetus suggests that fetal somatic growth may not be thyroid hormone dependent. The high rate of T4s in the euthyroid fetus may be important to development of fetal brain and of bone near term.