Abnormal Thyroid Hormones Up Risk of Gestational Diabetes

Thyroid dysfunction during the first half of pregnancy is associated with an increased risk of gestational diabetes, adding weight to the argument for thyroid screening among pregnant women.

Specifically, the longitudinal study suggests that a higher level of free triiodothyronine (fT3) may be involved in the pathophysiology of gestational diabetes, which might be because of de novo synthesis or increased conversion of free thyroxine (fT4) to T3.

The new study, by Shristi Rawal, PhD, of the National Institutes of Health (NIH), Bethesda, MD, and colleagues, was published online June 7 in the Journal of Clinical Endocrinology & Metabolism,

"We are the first ones to show that the fT3:fT4 ratio is significantly related to an elevated risk of gestational diabetes," senior author Cuilin Zhang, MD, MPH, PhD, also from NIH, told Medscape Medical News, noting that "this builds on previous work showing a relationship between the ratio and other markers of glucose metabolism."

Zhang explained that thyroid hormones are implicated in the etiology of gestational diabetes, but the topic remains controversial, and the debate about whether to test thyroid hormones in early pregnancy is ongoing.

"There's a lack of longitudinal data on thyroid function markers and risk of gestational diabetes, so this study aims to provide some relevant data to help address this research gap," Zhang said.

The authors note that their results, together with some previous work, support the potential benefits of thyroid screening among pregnant women.

"Our work provides another layer of evidence for the potential need for thyroid function screening in early to mid-pregnancy in terms of implications for gravid conditions like gestational diabetes," Zhang stressed, while cautioning that "we need to replicate this in another population study first before we can be certain about clinical recommendations."

fT3 Levels and fT3:fT4 Ratios Throughout Pregnancy

Miscarriages, premature birth, and adverse childhood health outcomes have all been associated with thyroid dysfunction in pregnancy.

In particular, high thyroid hormone levels have been linked to the development of gestational diabetes, which affects 2% to 10% of pregnancies in the United States, increasing the risk of premature delivery and hyperglycemia in the mother. Babies born to mothers with gestational diabetes are also more prone to developing hypoglycemia.

To gauge changes in thyroid function in early pregnancy, Rawal and colleagues prospectively investigated the association of fT3 levels and the fT3:fT4 ratio with gestational diabetes.

Because thyroid levels change as pregnancy progresses, these associations were analyzed separately for the first (gestational weeks 10–14) and second (weeks 15–26) trimesters.

The case-control study involved 107 pregnant women with gestational diabetes and 214 controls without the condition from the Fetal Growth Studies-Singleton cohort, a multiracial pregnancy cohort of 2802 women.

All participants attended four visits during the first and second trimesters of pregnancy at 12 clinical centers across the United States. Levels of fT3, fT4, and thyroid stimulating hormone were measured, and the fT3:fT4 ratio was calculated. Gestational diabetes status was determined from medical records.

After adjusting for thyroid autoimmunity status and major gestational diabetes risk factors including age, ethnicity, and pre-pregnancy body mass index (BMI), researchers estimated trimester-specific associations of thyroid markers with subsequent risk for gestational diabetes.

Examining Trajectory of Thyroid Hormone Changes Over Two Trimesters

Median fT4 levels were significantly lower in women who developed gestational diabetes. In contrast, median fT3 levels and the fT3:fT4 ratio were significantly higher in both the first and second trimester assessments prior to gestational diabetes diagnosis.

fT3 levels were significantly and positively associated with risk of gestational diabetes. The odds ratio (OR) for gestational diabetes, comparing the highest to lowest fT3 quartile, was 4.25 during the first trimester (P for trend = .001) and 3.89 during the second trimester (P for trend = .007).

Similarly, the corresponding risk estimates for gestational diabetes comparing the highest versus lowest fT3:fT4 ratio quartile were OR 8.6 and OR 13.6 during the first and second trimesters, respectively (both P for trend < .0001).

"Because our data are longitudinal on thyroid markers during pregnancy, we show the trajectory of how these hormones change over pregnancy," explained Zhang.

"Potentially, in the next step, we can look at how these thyroid hormones relate to fetal growth and outcomes. We have these data but they need to be analyzed."

The authors acknowledge that the case-control study is small; however, they add that strengths included longitudinal measurement of several thyroid function markers across pregnancy to reflect the changes during gestation, the fact that thyroid autoimmunity status was accounted for, and the sample was drawn from a multiracial cohort representative of the general population.

"It is still early, but if it is at all possible that a clinic can do a hormone test during the first prenatal visit, then it might be helpful to do so, especially in patients with a family history of gestational diabetes. If the fT3:fT4 ratio is high, then it might be good to be cautious of that patient's future risk of gestational diabetes," concluded Zhang.

Zhang and Rawal have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online June 7, 2018. Full text

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