Serum Free Thyroxine Concentration is Associated with Metabolic Syndrome in Euthyroid Subjects

Context: The association between thyroid hormones within the euthyroid range and metabolic syndrome is not clear. Aim: This study evaluated the relationship between thyroid hormones and metabolic syndrome and its components in euthyroid subjects. Design and setting: This is a cross-sectional population based study conducted within the framework of the cohort of the Tehran Thyroid Study. Participants: Out of 5786 subjects aged >= 20 years, 3755 euthyroid subjects without a history of thyroid disorders, diabetes, or use of steroids or lipid-lowering agents were investigated. Outcome measures: Body weight, waist circumference (WC), and blood pressure (BP) were measured. Serum concentrations of lipids and lipoproteins, fasting blood glucose (FBG), insulin, free T-4 (FT4), and thyrotropin (TSH) were assayed. Metabolic syndrome was determined by definition of the Joint Interim Statement adjusted for the Iranian population. Results: After adjustment for age, sex, and smoking, serum FT4 was significantly associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), WC, systolic BP, and diastolic BP; the associations that remained significant after further adjustment for body mass index (BMI) and the homeostasis model assessment index for insulin resistance (HOMA-IR) except for HDL-C. Serum TSH was associated only with TGs after adjustments for age, sex, smoking, and BMI, an association that disappeared after further adjustment for HOMA-IR. Serum FT4 was negatively associated (beta=-0.02, 95% confidence interval [CI: -0.03, -0.01]) and TSH was positively associated (beta=0.03 [CI: 0.01, 0.04) with insulin resistance. The prevalence of metabolic syndrome decreased from 30.1% in the lowest FT4 tertile to 22.4% in the highest FT4 tertile (p<0.001). The prevalence of other metabolic syndrome components decreased significantly from higher to lower FT4 tertiles. Higher FT4 values were associated with lower odds of metabolic syndrome (OR=0.96 [95% CI: 0.92, 0.99]; p=0.01). Conclusion: In euthyroid subjects, FT4, rather than TSH, is associated with risk of metabolic syndrome and its components.