Lower free thyroxin associates with a less favorable metabolic phenotype in healthy pregnant women

Abstract

Context: A lower free T 4 (fT4), within the euthyroid range, has been shown in adults to associate with an adverse metabolic phenotype. Thyroid physiology changes significantly during gestation and affects maternal and fetal well-being. Objective: The aim of the study was to test the hypothesis that a lower serum fT4 in healthy euthyroid pregnant women is related to a less favorable metabolic phenotype and to fetal or placental weight. Design, Setting, Patients, and Outcome Measures: We examined associations of thyroid function tests (TSH and fT4) and the free T 3 (fT3)-to-fT4 ratio (as a proxy of deiodinase activity) with a metabolic profile [preload and postload glucose, glycosylated hemoglobin (HbA1c), high molecular-weight (HMW)-adiponectin, homeostasis model of assessment for insulin resistance (HOMA-IR), and serum lipids] in 321 healthy pregnant women. All women were euthyroid and had negative anti-thyroid peroxidase antibodies. None received thyroid hormone replacement. Blood tests were performed in women between 24 and 28 wk gestation. Placentas and newborns were weighed at birth. Results: Circulating TSH did not relate to metabolic parameters, but decreasing fT4 and increasing fT3-to-fT4 ratio associated with a less favorable metabolic phenotype, as judged by higher postload glucose, HbA1c, fasting insulin, HOMA-IR, and triglycerides, and by a lower HMW-adiponectinemia (all P ≤ 0.005). In multiple regression analyses, fT4 was independently associated with HbA1c (β = -0.135; P = 0.038), HMW-adiponectin (β = 0.218; P < 0.001), and placental weight (β = -0.185; P < 0.005), whereas the fT3-to-fT4 ratio was independently associated with maternal body mass index (β = 0.265; P < 0.001), HMW-adiponectinemia (β = -0.237; P < 0.002), HOMA-IR (β = 0.194; P = 0.014), and placental weight (β = 0.174; P = 0.020). Conclusion: In pregnant women without a history of thyroid dysfunction, lower concentrations of fT4 and a higher conversion of fT4 to fT3, as inferred by changes in the fT3-to-fT4 ratio, were found to be associated with a less favorable metabolic phenotype and with more placental growth. Copyright © 2011 by The Endocrine Society.