Excess thyroid hormone associated with increased rates of miscarriage


CHICAGO – High levels of thyroid hormone in pregnant women can have a direct toxic effect on fetal development, according to a study in the August 11 issue of JAMA, the Journal of the American Medical Association.

According to background information in the article, thyroid hormone (TH) plays an important role in the development of the embryo and maturation of the fetus. Maternal hypothyroidism (an underactive thyroid gland) and hyperthyroidism (an overactive thyroid gland) have deleterious effects on the outcome of pregnancy. While the effects of TH deprivation on the fetus, independently from that on the mother, can be studied in infants with congenital hypothyroidism, this is not the case in those with fetal thyrotoxicosis (an overactive thyroid gland).

João Anselmo, M.D., of Hospital Divino Espírito Santo, Ponta Delgada, Azores-Portugal, and colleagues from the University of Chicago Hospitals studied the effects of TH excess on fetuses carried by mothers who, because of their resistance to TH (RTH) are normal despite high TH levels but who may carry normal fetuses that have been exposed to high maternal hormone levels. The study included 167 members of an Azorean family with RTH. Affected individuals had the RTH phenotype.

Thirty-six couples with complete information belonged to 1 of 3 groups: affected mothers (n=9), affected fathers (n=9), and unaffected relatives (n=18). "Mean miscarriage rates were 22.9 percent, 2.0 percent, and 4.4 percent, respectively. Affected mothers had an increased rate of miscarriage. They had marginally higher than expected numbers of affected offspring, i.e., 20 affected and 11 unaffected children, while affected fathers had 15 affected and 12 unaffected children. Unaffected infants born to affected mothers were significantly smaller than affected infants …," the authors write. "Our data show a 3- to 4-fold increase in the rate of miscarriage in affected mothers compared with that of spouses of affected fathers or unaffected first-degree relatives …"

"The data presented herein show, for the first time in humans, that high levels of TH can exert a direct toxic effect on fetal development. This is manifested by an increased rate of miscarriages and a lower birth weight of unaffected infants born to euthyroid mothers with high levels of TH. As expected, fetuses harboring a mutation that reduces the sensitivity to TH are protected from this toxic effect of TH excess.

Given the established importance of providing TH replacement to even mildly hypothyroid pregnant women, it is important to recognize that overreplacement appears to be equally detrimental," the authors conclude.
(JAMA. 2004;292:691-695. Available post-embargo at JAMA.com)

Editor's Note: This work was supported in part by grants from the National Institutes of Health. Dr. Refetoff is Academic Associate for Quest Diagnostics Inc.

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