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

Abstract

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.

Impact of Adjusting for the Reciprocal Relationship Between Maternal Weight and Free Thyroxine During Early Pregnancy

“…In that study, BMI averaged 2.9 kg/m 2 higher (17 lb) in association with FT4 concentrations below the 2.5th centile. Other recent studies have documented similar relationships (4)(5)(6)(7). Depending upon the nature of this relationship across the broader BMI or weight spectrum, a maternal weight effect might partially explain variations among individual FT4 ranges, thereby accounting for a portion of overall population variability.…”

“…In their analysis of a cohort of pregnant women, Bassols et al provide data demonstrating a less favorable metabolic phenotype in association with lower FT4, as defined by higher fasting and postload insulin, HOMA-IR, HbA1c, and triglycerides, and with lower adiponectin (4). Among the 321 early third trimester euthyroid women in that study, the free triiodothyronine (FT3)/FT4 ratio was independently associated with BMI in a multiple regression model, suggesting that relatively increased FT3 production may compensate for lower FT4 concentrations.…”

Thyrotropin Levels Are Associated with Cardiometabolic Risk Factors in Euthyroid Adolescents

“…Given the role of thyroid hormones in the regulation of energy expenditure and thermogenesis (40), and the increasingly well-established relations between subtle alterations in TSH, thyroid hormone levels, and cardiometabolic risk factors (13,(17)(18)(19)(20)(21)23,24,28,29,35), there has been interest in assessing the effects of weight loss on thyroid hormone levels. In a study of adult overweight or obese otherwise healthy subjects undergoing a controlled lifestyle modification program, modest weight loss (6.5 -1.0%) resulted in reductions in TT3 without significant changes in TSH or fT4.…”

“…The present assessment of an unselected U.S. population (by default devoid of specific clinical indications for testing) minimizes the risk of selection bias. While other published analyses of population databases have not addressed any potential racial or ethnic differences (10,11,(17)(18)(19)21,(23)(24)(25)28,29), this NHANES cohort consisted of participants who predominantly selfidentified as non-Hispanic white, non-Hispanic black, Mexican-American, or other Hispanic. The lack of any race/ ethnicity differences in TSH and thyroid hormones suggests that with respect to race/ethnicity, other factors such as BMI (which did show ethnicity differences in the analysis) still play a greater role than the thyroid axis in determining overall cardiometabolic risk.…”

“…The ratio of T3 to T4 (or fT3 to fT4) has been proposed as a better estimate of tissuespecific deiodinase activity in the conversion of T4 to T3 (22). Indeed, in healthy pregnant women, an increasing fT3:fT4 ratio has been associated with decreased glucose tolerance, higher triglycerides, and higher maternal BMI, while no association between TSH and these same metabolic parameters was found (23). The relationship between higher fT3:fT4 ratios and more unfavorable metabolic phenotypes was further supported by the finding that in euthyroid healthy individuals, both higher fT3 levels and a higher fT3:fT4 ratio were directly related to BMI, waist circumference, and a less favorable lipid profile (24).…”