Hyperthyroidism and High-Normal Free T4 Levels Linked to Hypertensive Disorders in Pregnancy

Hyperthyroidism and high-normal free T4 levels in pregnancy are associated with an increased risk for pregnancy-induced hypertension and preeclampsia, according to findings from a population-based cohort study. The study was published online ahead of print in the Journal of Clinical Endocrinology and Metabolism.

“Hypertensive disorders during pregnancy, including preeclampsia, are not only associated with an increased risk of maternal and fetal mortality and morbidity during pregnancy, but also with various maternal and child cardiovascular, renal and psychiatric complications in later life,” said lead author Marco Medici, MD PhD, of the Erasmus Medical Center in Rotterdam, The Netherlands. “Despite this, only a limited number of risk factors for the development of these hypertensive disorders are known,” he said.

“The current study shows that not only hyperthyroidism, but also minor variation in thyroid function within the normal range (ie, high-normal FT4 levels) is associated with an increased risk of hypertensive disorders,” Dr. Medici said. “These results suggest that thyroid function testing should be added to the diagnostic work-up of hypertensive disorders during pregnancy. However, the potential clinical benefits of early-pregnancy thyroid function testing and treatment of these women are currently unknown, and remains to be investigated in future studies,” he said.

Data Derived From the Generation R Study
The study included 5,153 pregnant women enrolled in the Generation R Study, none of whom had pre-existing thyroid disease, twin pregnancies, fertility treatments, or used medications that interfered with thyroid function. Blood samples were taken early in pregnancy (mean, 13.5 weeks) and levels of thyroid-stimulating hormone, and free T4 were measured.

A total of 345 women (6.7%) developed a hypertensive disorder: 209 (4.1%) developed pregnancy-induced hypertension and 136 (2.6%) developed preeclampsia.

Hyperthyroidism Linked to Fourfold Risk of Pregnancy-Induced Hypertension
The incidence of hypertensive disorders was higher in women with hyperthyroidism than in women with normal thyroid function (13.7% vs 6.2%; P=0.005).  When divided into subtypes of hypertensive disorders, overt hyperthyroidism was linked to a 4.2-fold higher risk of pregnancy-induced hypertension and a trend toward a higher risk of preeclampsia. Women with high-normal FT4 levels (17.1–21.9 pmol/L) had an increased risk for hypertensive disorders (OR, 1.62; P=0.03), mainly resulting from an increased risk of preeclampsia (OR, 2.06; P=0.04).

Other thyroid disorders such as hypothyroidism or hypothyroxinemia were not linked to an increased risk for hypertensive disorders.

Study Strengths
“The primary findings were that hyperthyroidism, as well as FT4 concentrations within the upper limits of the normal range, were both associated with an increased risk of hypertensive disorders, which included pregnancy-induced hypertension and preeclampsia,” commented Angela M. Leung, MD, MSc, Clinical Assistant Professor of Medicine, Division of Endocrinology, UCLA David Geffen School of Medicine, Los Angeles, CA. “The study’s strengths are in its large number of subjects, adjustment for multiple potential confounders, and study population that was overall iodine-sufficient,” Dr. Leung said.

“As the authors note, further research is necessary to replicate the findings and determine whether intervention (ie, treatment of hyperthyroidism) would be beneficial in decreasing the risks of developing hypertension-related disorders during pregnancy,” Dr. Leung said.

October 20, 2014

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