Women treated for subclinical hypothyroidism (SCH) during pregnancy are less likely to experience pregnancy loss, a new study shows, but they face a greater risk of complications such as preterm delivery, gestational diabetes and pre-eclampsia.1
While the new research doesn’t settle the ongoing controversy surrounding the question of whether pregnant women with SCH should receive thyroid-hormone replacement therapy, it may help identify the point at which treatment tips toward overall benefit and away from risk.
“Continuing to offer thyroid hormone treatment to decrease the risk of pregnancy loss is reasonable for women with TSH concentrations of 4.1-10.0 mIU/L,” said the study’s lead author, Spyridoula Maraka, M.D., a research collaborator with Mayo Clinic and assistant professor at the University of Arkansas for Medical Sciences and the Central Arkansas Veterans Health Care System. “However, given the smaller magnitude of effect in women with lower TSH levels of 2.5-4.0 mIU/L, and in light of the possible increased risk of other adverse events, treatment may need to be withheld in this group.”
Indeed, given the findings of their study, published in The BMJ, Maraka and her co-authors have expressed concern that pregnant women whose levels of thyroid stimulating hormone (TSH) measure in the 2.5-4.0 mIU/L range are being over-treated.
A new set of guidelines issued by the American Thyroid Association (ATA) buoys the conclusions of the BMJ study. “In light of accumulating evidence suggesting that adverse obstetric outcomes may occur at lower TSH thresholds in thyroperoxidase (TPO) positive women, the ATA has revised its 2011 guidelines,” said Elizabeth Pearce, M.D., associate professor of medicine at Boston University School of Medicine and co-chair of the ATA pregnancy guidelines task force.
The guidelines recommend taking into account TPO antibody status when deciding whether or not to treat subclinical hypothyroidism in pregnant women. Treatment is no longer recommended for TPO negative women with serum TSH values <4.0 mIU/L, thus echoing the recent study’s concern about over-treatment of women with TSH levels of 2.5 - 4.0 mIU/L.
Dr. Pearce noted, however, that the recent BMJ study was observational and that randomized, controlled clinical trials are needed to definitively determine whether or not thyroid replacement therapy improves obstetric outcomes in subclinically hypothyroid pregnant women.
The BMJ study looked at 5,405 pregnant women with subclinical hypothyroidism—defined as untreated TSH concentrations of 2.5-10 mIU/L—and determined that those treated with thyroid-hormone therapy were 38% less likely to experience pregnancy loss compared with those who were not treated. But the benefit was seen only in women with pre-treatment TSH levels of 4.1 -10 mIU/L.
The reduced risk of pregnancy loss was not observed in those with pre-treatment TSH levels of 2.5 - 4.0 mIU/L. In addition, this group of women had significantly higher chances of developing gestational hypertension—which can leadto pre-eclampsia—than those with similar TSH levels who were not treated.
Subclinical hypothyroidism—essentially a mildly underactive thyroid gland—is defined as having elevated TSH levels with concurrent normal thyroid hormone concentrations. The condition is estimated to affect up to 15% of pregnancies in the U.S. and 14% in Europe.
Thyroid hormone is critical during pregnancy for the healthy development of the fetal brain and nervous system.2 Research has found an association between both low and high maternal free thyroxine levels during pregnancy and low childhood IQ; researchers have also said that thyroid replacement treatment (levothyroxine), prescribed for subclinical hypothyroidism, may be a risk factor in the association between high maternal free thyroxine and low child IQ. 3 But these questions remain unsettled.
Overt hypothyroidism—when TSH levels are increased and the free thyroxine level is low—can cause severe symptoms and is associated with an increased incidence of infertility and miscarriage, both in women who are trying to conceive or are already pregnant, according to the ATA.4 “It’s clear that overt hypothyroidism should be treated with thyroid hormone replacement, usually levothyroxine.”