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

Yi-Cheng Chang; Shih-Che Hua; Chia-Hsuin Chang; Wei-Yi Kao; Hsiao-Lin Lee; Lee-Ming Chuang; Yen-Tsung Huang; Mei-Shu Lai

doi:10.3390/jcm8060817

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

J Clin Med. 2019 Jun 7;8(6):817. doi: 10.3390/jcm8060817.

Authors

Yi-Cheng Chang^{1

2

3

4}, Shih-Che Hua⁵, Chia-Hsuin Chang^{6

7

8}, Wei-Yi Kao⁹, Hsiao-Lin Lee^{10

11}, Lee-Ming Chuang^{12

13

14

15}, Yen-Tsung Huang¹⁶, Mei-Shu Lai¹⁷

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. b83401040@gmail.com.
² Department of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan. b83401040@gmail.com.
³ Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei 100, Taiwan. b83401040@gmail.com.
⁴ Institute of Biomedical Science, Academia Sinica, Taipei 115, Taiwan. b83401040@gmail.com.
⁵ Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Martin De Porres Hospital, ChiaYi 600, Taiwan. tedshua@gmail.com.
⁶ Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. chiahsuin123@yahoo.com.tw.
⁷ Department of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan. chiahsuin123@yahoo.com.tw.
⁸ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan. chiahsuin123@yahoo.com.tw.
⁹ MJ Health Screening Center, Taipei 100, Taiwan. cutesttuna@gmail.com.
¹⁰ Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. leehsiaolin1103@gmail.com.
¹¹ Department of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan. leehsiaolin1103@gmail.com.
¹² Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. leeming@ntu.edu.tw.
¹³ Department of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan. leeming@ntu.edu.tw.
¹⁴ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan. leeming@ntu.edu.tw.
¹⁵ Graduate Institute of Molecular Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. leeming@ntu.edu.tw.
¹⁶ Institute of Statistical Science, Academia Sinica, Taipei 115, Taiwan. ythuang@stat.sinica.edu.tw.
¹⁷ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan. mslai@ntu.edu.tw.

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.

Keywords: cardiometabolic risks; hypertension; metabolic syndrome; obesity; thyroid-stimulating hormone.