To study the fetal effects of excess maternal thyroid hormone (TH).
Of the 36 couples in this study, 9 included women with TH resistance (RTH) who were euthyroid despite high TH levels, 9 included men with this condition, and 18 were unaffected. Mean miscarriage rates were 22.9%, 2.0%, and 4.4%, respectively. Infants without RTH who were born to mothers with the condition were significantly smaller than infants who shared their mother’s TH status.
Animal studies suggest that both hyperand hypothyroidism are associated with increased numbers of malformations and poor reproductive outcomes. In humans, hyperthyroidism is usually associated with thyroid autoantibodies, so it is unclear whether the increased rate of miscarriages seen with this condition is related to the elevated circulating thyroid hormone, to autoantibodies, or to both. To explore this, Anselmo et al took advantage of a “natural experiment” in a large extended family. This family harbored a single gene mutation, inherited autosomally, that made the TH receptor resistant to thyroid hormone.
Women with this mutation have, on average, twice the circulating TH level and normal thyroid-stimulating hormone (TSH). They are clinically euthyroid, without autoantibodies, but elevated TH levels pass to the fetus, which may or may not be genetically affected by the same condition.
Infants with mutation are protected
Anselmo et al found normal birth weight among babies affected by the same mutation as their mother. Presumably, these infants are euthyroid and grow normally despite elevated circulating TH. In contrast, infants who lack the mutation are significantly smaller due to the maternal environment of elevated circulating TH.
Unfortunately, although Anselmo and colleagues performed a thorough and thoughtful analysis, they did not indicate how prevalent this condition is in the general population.
This study supports other evidence that elevated TH is associated with early fetal loss. This information can be generalized to patients with thyroid disease. Women on thyroid replacement should be monitored to ensure that their TH is in the normal range, and physicians should make every attempt to normalize TH in women with thyrotoxicosis.