Thyroid Hormones and the Metabolic Syndrome.

European thyroid journal 06/2013; 2(2):83-92. DOI: 10.1159/000351249
Source: PubMed

ABSTRACT Clustering of various metabolic parameters including abdominal obesity, hyperglycaemia, low high-density lipoprotein cholesterol, elevated triglycerides and hypertension have been used worldwide as metabolic syndrome to predict cardiometabolic risk. Thyroid dysfunction impacts on various levels of these components.
The purpose of the present review is to summarize available data on thyroid hormone-dependent action on components of the metabolic syndrome.
A PubMed search for any combination of hyperthyroidism, thyrotoxicosis or hypothyroidism and metabolic syndrome, blood pressure, hypertension, hyperlipidaemia, cholesterol, high-density lipoprotein cholesterol, glucose, diabetes mellitus, body weight or visceral fat was performed. We included papers and reviews published between 2000 and today but accepted also frequently cited papers before 2000.
There is convincing evidence for a major impact of thyroid function on all components of the metabolic syndrome, reflecting profound alterations of energy homeostasis at many levels.
Even though the interactions shown in animal models and man are complex, it is evident that insulin sensitivity is highest and adverse thyroid effects on the metabolic system are lowest in euthyroid conditions.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.
    Physiological Reviews 04/2014; 94(2):355-82. DOI:10.1152/physrev.00030.2013 · 29.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of obesity and Type 2 diabetes mellitus (T2DM) among children and adolescents is rising. Thyroid function has been associated with insulin resistance. There is scarce information about how thyroid function could be related with cardiovascular risk or glucose homeostasis in adolescent. To analyze how thyroid function is associated with insulin resistance and another cardiovascular risk factors in healthy adolescents with risk factors to develop diabetes. A prospective cross-sectional analysis was carried out on euthyroid, adolescents. considered at high risk to develop Type 2 diabetes. Fasting blood samples were obtained. Thyroid function test and another cardiometabolic parameters were assessed. A 75 grams oral glucose tolerance test was performed to calculate insulin resistance. One hundred adolescents were evaluated. The mean age was 15.9 ± 0.8 years, There is a negative correlation between Fasting insulin, post glucose load insulin and HOMA IR. There were no correlation with Matsuda index. We could not found any correlation with TSH values. We found a correlation between fasting insulin, HOMA IR and serum thyroid hormones, we did not find any relation with serum TSH. In euthyroid adolescents with risk factors to develop diabetes.
    Diabetology and Metabolic Syndrome 01/2015; 7:16. DOI:10.1186/s13098-015-0011-x · 2.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The concept is emerging that low-normal thyroid function, i.e., either higher thyroid-stimulating hormone or lower free thyroxine levels within the euthyroid reference range, could contribute to the development of atherosclerotic cardiovascular disease. It is possible that adverse effects of low-normal thyroid function on cardiovascular outcome may be particularly relevant for specific populations, such as younger people and subjects with high cardiovascular risk. Low-normal thyroid function probably relates to modest increases in plasma total cholesterol, low density lipoprotein cholesterol, triglycerides and insulin resistance, but effects on high density lipoprotein (HDL) cholesterol and non-alcoholic fatty liver disease are inconsistent. Low-normal thyroid function may enhance plasma cholesteryl ester transfer, and contribute to an impaired ability of HDL to inhibit oxidative modification of LDL, reflecting pro-atherogenic alterations in lipoprotein metabolism and HDL function, respectively. Low-normal thyroid function also confers lower levels of bilirubin, a strong natural anti-oxidant. Remarkably, all these effects of low-normal thyroid functional status appear to be more outspoken in the context of chronic hyperglycemia and/or insulin resistance. Collectively, these data support the concept that low-normal thyroid function may adversely affect several processes which conceivably contribute to the pathogenesis of atherosclerotic cardiovascular disease, beyond effects on conventional lipoprotein measures.
    Nutrients 02/2015; 7(2):1352-77. DOI:10.3390/nu7021352 · 3.15 Impact Factor

Preview (2 Sources)

Available from