High TSH Level within Normal Range Is Associated with Obesity, Dyslipidemia, Hypertension, Inflammation, Hypercoagulability, and the Metabolic Syndrome: A Novel Cardiometabolic Marker

Abstract

(1) Background: Overt and subclinical hypothyroidism has been associated with increased cardiometabolic risks. Here we further explore whether thyroid function within normal range is associated with cardiometabolic risk factors in a large population-based study. (2) Methods: We screened 24,765 adults participating in health examinations in Taiwan. Participants were grouped according to high-sensitive thyroid-stimulating hormone (hsTSH) level as: <50th percentile (0.47–1.48 mIU/L, the reference group), 50–60th percentile (1.49–1.68 mIU/L), 60–70th percentile (1.69–1.94 mIU/L), 70–80th percentile (1.95–2.3 mIU/L), 80–90th percentile (2.31–2.93 mIU/L), and >90th percentile (>2.93 mIU/L). Cardiometabolic traits of each percentile were compared with the reference group. (3) Results: Elevated hsTSH levels within normal range were dose-dependently associated with increased body mass index, body fat percentage, waist circumferences, blood pressure, hemoglobin A1c (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high homeostasis model of assessment of beta-cell (HOMA-β), triglycerides, total cholesterols, fibrinogen, and uric acids (p-for-trend <0.001), but not with fasting glucose levels. The association remained significant after adjustment of age, sex, and lifestyle. As compared to the reference group, subjects with the highest hsTSH percentile had significantly increased risk of being overweight (adjusted odds ratio (adjOR): 1.35), increased body fat (adjOR: 1.29), central obesity (adjOR: 1.36), elevated blood pressure (adjOR: 1.26), high HbA1c (adjOR: 1.20), hyperinsulinemia (adjOR: 1.75), increased HOMA-IR (adjOR: 1.45), increased HOMA-β (adjOR: 1.40), hypertriglyceridemia (adjOR: 1.60), hypercholesterolemia (adjOR: 1.25), elevated hsCRP (adjOR: 1.34), increased fibrinogen (adjOR: 1.45), hyperuricemia (adjOR: 1.47), and metabolic syndrome (adjOR: 1.42), but significant risk of low fasting glucose (adjOR: 0.89). Mediation analysis indicates that insulin resistance mediates the majority of the association between thyroid hormone status and the metabolic syndrome. (4) Conclusion: Elevated hsTSH within the normal range is a cardiometabolic risk marker associated with central obesity, insulin resistance, elevated blood pressure, dyslipidemia, hyperuricemia, inflammation, and hypercoagulability.

Importance of thyroid-stimulating hormone levels in liver disease

“…Similar to our study, significant positive associations between TSH, AST, and total bilirubin levels have been reported previously [5,6]. A previous study suggested the role of high TSH levels as a cardiometabolic risk marker and that dyslipidemia, hyperglycemia, and liver abnormalities were associated with high TSH levels [23]. In the present study, however, we could not evaluate such laboratory findings.…”

“…Elevated TSH levels and hypothyroidism have been associated with the pathogenesis of NAFLD [23][24][25]. Other factors such as obesity and metabolic syndrome were also considered risk factors for subclinical hypothyroidism [26].…”

The association between dyslipidemia and the incidence of chronic kidney disease in the general Zhejiang population: a retrospective study

“…Before this study, we used the similar data to analyze the relationship between serum uric acid and CKD in the general population, and concluded that time-mean serum uric acid is an independent risk factor for CKD [18]. Dyslipidemia and hyperuricemia are important diseases that affect human health [19]. Therefore, we specifically studied the relationship between dyslipidemia and CKD.…”

Correlation Between Serum TSH Levels Within Normal Range and Serum Lipid Profile

“…In contrast, Jiaoyue et al found that after adjusting for age and other confounding factors, there is no correlation between TSH level and blood lipids [10]. However, a linear dose-dependent correlation between high TSH level in the normal range and dyslipidemia, possibly mediated by the effect of thyroid hormones on insulin sensitivity, was revealed in a large population-based study [11]. In patients with normal thyroid function and newly diagnosed asymptomatic coronary heart disease, the increased TSH level may have adverse effects on blood lipids and may also be a risk factor for hypercholesterolemia and hypertriglyceridemia [12].…”