Lower Free Thyroxin Associates with a Less Favorable Metabolic Phenotype in Healthy Pregnant Women

Abstract

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. 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. 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). 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.