The Association Between Thyroid Function and Incidence of Metabolic Syndrome in Euthyroid Subjects

Tianjin Chronic Low-Grade Systemic Inflammation and Health Cohort Study

Yeqing Gu; Yanyan Wang; Qing Zhang; Li Liu; Ge Meng; Zhanxin Yao; Hongmei Wu; Yang Xia; Xue Bao; Hongbin Shi; Honglei Wang; Shaomei Sun; Xing Wang; Ming Zhou; Qiyu Jia; Kun Song; Kaijun Niu


Clin Endocrinol. 2018;88(5):735-743. 

In This Article

Abstract and Introduction


Objective Thyroid hormones (THs) are primarily responsible for the regulation of energy homeostasis and metabolism. However, few prospective studies have assessed the association between THs and metabolic syndrome (MetS) in a general population. We therefore designed a cohort study to examine whether serum TH levels within the reference range are predictive factors for developing MetS in adults.

Design Prospective cohort study.

Participants A prospective study (n = 6119) was performed in Tianjin, China. Participants without a history of MetS were followed up for 1 to 3 years with a median follow–up duration of 2 years.

Measurements Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid–stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay. MetS was defined in accordance with the criteria of the American Heart Association scientific statements of 2009. THs, TSH levels and MetS were assessed yearly during the follow–up. Adjusted Cox proportional hazards regression models were used to assess the associations between FT3, FT4 and TSH quintiles and MetS.

Results The incidence of MetS was 17.7% (96 per 1000 person–years). In the final multivariate models, the hazard ratios (95% confidence interval) for MetS across serum FT3 quintiles were 1.00 (reference), 1.03 (0.84, 1.25), 1.14 (0.94, 1.38), 1.09 (0.90, 1.32) and 1.33 (1.11, 1.61), respectively (P for trend <.01). However, no significant associations between FT4, TSH and MetS were observed.

Conclusions This population–based prospective cohort study suggests that increased serum FT3 level, rather than FT4 and TSH, is an independent predictor for developing MetS in euthyroid subjects.


Metabolic syndrome (MetS) is a complex disease characterized by a cluster of cardiovascular disease (CVD) risk factors, and it appears to directly promote the development of atherosclerotic cardiovascular disease.[1] Its components include central obesity, hyperglycaemia, hypertriglyceridaemia, decreased high–density lipoprotein cholesterol (HDL) and elevated blood pressure (BP). The Third National Health and Nutritional Survey indicated that approximately 22% of US adults (24% after age adjustment) have MetS.[2] With the development of economy, the prevalence of MetS has increased greatly in developing countries as well. The overall prevalence of MetS in China has increased considerably from 13.7% between 2000 and 2001 to 27.4% between 2009 and 2010.[3]

Clarifying the common pathological processes of MetS is a crucial step towards providing their early prevention and treatment. Thyroid hormones (THs) are primarily responsible for the regulation of energy homeostasis and metabolism.[4] TH signalling modulates energy expenditure through both central and peripheral pathways.[5] They can stimulate the expression of uncoupling proteins in the mitochondria of fat and skeletal muscle, modulate adrenergic receptor numbers by enhancing responsiveness of catecholamines and thus regulate metabolic rate and body weight.[6] In addition, there have been reports suggesting an association between THs and insulin resistance, lipoprotein metabolism and BP.[7] As obesity, blood glucose, blood lipid and BP are all features of MetS, it is hypothesized that THs are a useful predictive factor for developing MetS. On the other hand, thyroid–stimulating hormone (TSH) binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of THs by negative feedback inhibition.[8]

To date, only several cross–sectional studies have evaluated the association between THs or TSH and MetS in euthyroid subjects,[7,9–19] and a few studies assessed just MetS components individually rather than the syndrome as a whole.[7,20–24] Additionally, only one cohort study evaluated the association between TSH levels and the prevalence and incidence of the MetS in older people (aged 70–79 years).[25] Based on these finding, we conducted a prospective cohort study to evaluate how the serum TH concentrations within the reference range as well as TSH levels are associated with the incidence of MetS in an adult population of euthyroid adults.