Fetal Loss Associated With Excess Thyroid Hormone Exposure

Abstract

Both maternal hypothyroidism and hyperthyroidism have adverse effects on pregnancy outcomes. The effects of thyroid hormone (TH) deprivation on the fetus can be studied in infants having congenital hypothyroidism, but this is not the case for those with fetal thyrotoxicosis. This retrospective family study examined the effects of excessive TH in fetuses whose mothers were resistant to TH (THR) secondary to mutations of the TH receptor β gene. These women maintain an euthyroid state despite high TH levels. The study focused on 167 members of an Azorean family with RTH. Those affected had high serum levels of free thyroxine and triiodothyronine but no suppression of thyrotropin. They had the Arg2 (→) gln mutation of the TH receptor β gene. Among 36 couples with complete information, 9 had an affected mother, 9 an affected father, and 18 were unaffected. Miscarriage rates averaged 22.9%, 2.0%, and 4.4%, respectively. Affected mothers had 20 affected and 11 unaffected children, whereas affected fathers had 15 affected and 12 unaffected children. Unaffected infants born to affected mothers were significantly smaller than affected infants. Only in unaffected infants born to affected mothers were blood levels of thyrotropin undetectable. These findings indicate that high levels of TH may have direct toxic effects on fetal development. They include an increased risk of miscarriage and lower birth weights of unaffected infants born to euthyroid mothers with high TH levels. There is no question that even mildly hypothyroid pregnant women should have TH replacement, but it also must be recognized that overreplacement may have adverse effects on the developing fetus.