Overactive Thyroid Tied to Miscarriage Risk

Study finds too much of hormone in pregnancy can harm fetus

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HealthDay Reporter

TUESDAY, Aug. 10, 2004 (HealthDayNews) -- Researchers say they have found the first evidence that high levels of thyroid hormone in pregnant women can have a deadly effect on the fetus.

This negative effect could be seen in a tripling of the risk of miscarriage and a reduction in the average weight of the babies who survived, their new study says.

Thyroid hormone is critical to the development of the fetus, and both excessive and insufficient levels of it can result in a higher rate of miscarriage and other problems.

But while it has been possible to separate the effect of too little hormone on the fetus and on the mother, it has not been possible to do so when the issue is too much hormone.

In fact, until now, researchers had thought that a higher rate of miscarriages among women with overactive thyroid glands was due to the presence of antibodies, not to the hormone itself, said Dr. Samuel Refetoff, senior author of a paper appearing in the Aug. 11 issue of the Journal of the American Medical Association.

According to the authors, this finding appears to cast doubt on the conclusion of a study that appeared in the July 15 issue of the New England Journal of Medicine. It found that women with underactive thyroid gland should increase their dosage of hormone by approximately 30 percent as soon as a pregnancy was confirmed.

"Thirty percent is not a magic number," said Refetoff, a professor of medicine and pediatrics at the University of Chicago. "The issue is that too little hormone can be detrimental, but too much hormone can be bad if not worse. Women should not be given more hormone just because they are pregnant. They should be tested and given the right amount only if they need it."

Others, however, believe it is too early to draw such conclusions. "This study is not enough to say that over-replacement is detrimental. It certainly is concerning," said Dr. Andrei Rebarber, an associate professor of obstetrics and gynecology at New York University School of Medicine. "You never want to give anybody overmedication, but this study doesn't really tell you that that was the responsible cause. They didn't analyze the miscarriages."

The current study was made possible by a discovery Refetoff made almost 40 years ago of an unusual genetic mutation that causes a defect in the thyroid hormone receptor. The receptor can be likened to the lock into which a key (in this case, the hormone) must fit.

"In order for the hormone to have an effect, it has to make contact with the receptor," Refetoff explained. "The mutation in the receptor creates a situation where the key doesn't fit perfectly, so you need more hormone to have a normal reaction." This results in the unusual situation of having excess amounts of thyroid without the weight loss, anxiety and elevated heart rate normally associated with the condition.

This study looked at pregnancies in 36 married couples in the Azores, west of Portugal. The mother or father in 18 of the couples had the mutation, while both parents in the other 18 couples did not.

Mothers with the mutation had a 23.7 percent rate of miscarriage, about three times the rate for couples in which only the father had the mutation (6.7 percent) or neither parent had the mutation (8.8 percent). Rebarber said the miscarriage rate in the United States is actually 30 percent.

Infants born to mothers with the mutation had a 20 percent lower-than-average birth weight.

And, while theoretically mothers with this mutation have a 50/50 chance of giving birth to children with the mutation, in fact, two-thirds of the children born in this study had the defect. This would suggest that the fetuses that were miscarried did not possess the mutation. "They gave birth to more affected babies than normal, implying that the babies that were [naturally] aborted were normal babies because they got too much thyroid hormone," Refetoff said.

Although intriguing, other experts think the findings should be interpreted with caution.

"It is confined to a small group of people, and whether this can be carried over to other populations is a little uncertain in my mind," said Dr. Gene Burkett, a professor of obstetrics and gynecology at the University of Miami School of Medicine. "Secondly, I don't know that he carefully controlled for other factors which would account for the high pregnancy loss."

More information

For more on thyroid issues during pregnancy, visit Columbia University.

SOURCES: Samuel Refetoff, M.D., professor, medicine and pediatrics, and committees, genetics and molecular medicine, University of Chicago; Gene Burkett, M.D., professor, obstetrics and gynecology, University of Miami School of Medicine, Miami; Andrei Rebarber, M.D., associate professor, obstetrics and gynecology, New York University School of Medicine, and director, division of maternal-fetal medicine, New York University Medical Center, New York City; Aug. 11, 2004, Journal of the American Medical Association

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