title: Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders.
abstract: BACKGROUND
  Subclinical hypothyroidism may adversely affect the development of cardiovascular disease (CVD). Less is known about the role of low-normal thyroid function, that is higher thyroid-stimulating hormone and/or lower free thyroxine levels within the euthyroid reference range, in the development of cardio-metabolic disorders. This review is focused on the relationship of low-normal thyroid function with CVD, plasma lipids and lipoprotein function, as well as with metabolic syndrome (MetS), chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  This narrative review, which includes results from previously published systematic reviews and meta-analyses, is based on clinical and basic research papers, obtained via MEDLINE and PubMed up to November 2014.
  
  
  RESULTS
  Low-normal thyroid function could adversely affect the development of (subclinical) atherosclerotic manifestations. It is likely that low-normal thyroid function relates to modest increases in plasma total cholesterol, LDL cholesterol and triglycerides, and may convey pro-atherogenic changes in lipoprotein metabolism and in HDL function. Most available data support the concept that low-normal thyroid function is associated with MetS, insulin resistance and CKD, but not with high blood pressure. Inconsistent effects of low-normal thyroid function on NAFLD have been reported so far.
  
  
  CONCLUSIONS
  Observational studies suggest that low-normal thyroid function may be implicated in the pathogenesis of CVD. Low-normal thyroid function could also play a role in the development of MetS, insulin resistance and CKD, but the relationship with NAFLD is uncertain. The extent to which low-normal thyroid function prospectively predicts cardio-metabolic disorders has been insufficiently established so far.
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Lynnda J N
authors.initials: LJ
authors.lastname: van Tienhoven-Wind
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D058070:Asymptomatic Diseases; D002318:Cardiovascular Diseases / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism*; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism; D012307:Risk Factors; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008078:Cholesterol, LDL; D014280:Triglycerides; D013972:Thyrotropin; D013974:Thyroxine
keywords: Cardiovascular disease; chronic kidney disease; lipids; low-normal thyroid function; metabolic syndrome; nonalcoholic fatty liver disease; obesity; thyroid hormones; thyroid-stimulating hormone