Thyroid Function Is Associated with Components of the Metabolic Syndrome in Euthyroid Subjects

TLDR

Thyroid disease and the metabolic syndrome are both linked to cardiovascular disease, and the metabolic syndrome is defined by the National Cholesterol Education Program's Adult Treatment Panel III criteria. The study aimed to test whether thyroid function within the normal range in euthyroid adults is associated with metabolic syndrome components such as lipids and insulin resistance. The cross‑sectional study included 2,703 euthyroid adults from a Dutch city, excluding those on thyroid or diabetes medication, and calculated insulin resistance using the homeostasis model assessment (HOMA‑IR) from fasting insulin and glucose. Lower free T4 within the normal range correlated with higher total cholesterol, LDL, triglycerides, lower HDL, higher blood pressure, and greater insulin resistance, while TSH showed a modest positive association with insulin resistance, suggesting low normal thyroid function elevates cardiovascular risk.

Abstract

Thyroid disease and the metabolic syndrome are both associated with cardiovascular disease.The aim of this study was to explore the hypothesis that thyroid function, in euthyroid subjects, is associated with components of the metabolic syndrome, including serum lipid concentrations and insulin resistance.A total of 2703 adult inhabitants of a middle-sized city in The Netherlands participated in this cross-sectional study. Subjects who were not euthyroid were excluded, as were subjects taking thyroid medication, medication for diabetes, and subjects for whom medication data were not available (n = 1122). Homeostasis model assessment for insulin resistance (HOMA-IR) (mU*mmol/liter2) was calculated as fasting insulin (mU/liter) times fasting glucose (mmol/liter) divided by 22.5. The metabolic syndrome was defined according to National Cholesterol Education Program's Adult Treatment Panel III criteria.After adjustment for age and sex, free T4 (FT4) was significantly associated with total cholesterol [standardized beta (beta) = -0.059; P = 0.014], low-density lipoprotein cholesterol (beta = -0.068; P = 0.004), high-density lipoprotein cholesterol (beta = 0.100; P < 0.001), and triglycerides (beta = -0.102; P < 0.001). Both FT4 and TSH were significantly associated with HOMA-IR (beta = -0.133; P < 0.001 and beta = 0.055; P = 0.024, respectively). Median HOMA-IR increased from 1.42 in the highest tertile of FT4 to 1.66 in the lowest tertile of FT4. FT4 was significantly related to four of five components of the metabolic syndrome (abdominal obesity, triglycerides, high-density lipoprotein cholesterol, and blood pressure), independent of insulin resistance.We have demonstrated an association between FT4 levels within the normal reference range and lipids, in accordance with the earlier observed association between (sub)clinical hypothyroidism and hyperlipidemia. Moreover, low normal FT4 levels were significantly associated with increased insulin resistance. These findings are consistent with an increased cardiovascular risk in subjects with low normal thyroid function.