Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders

Eur J Clin Invest. 2015 May;45(5):494-503. doi: 10.1111/eci.12423. Epub 2015 Mar 9.


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).

Materials and 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.

Keywords: Cardiovascular disease; chronic kidney disease; lipids; low-normal thyroid function; metabolic syndrome; nonalcoholic fatty liver disease; obesity; thyroid hormones; thyroid-stimulating hormone.

Publication types

  • Review

MeSH terms

  • Asymptomatic Diseases
  • Cardiovascular Diseases / metabolism*
  • Cholesterol, LDL / metabolism
  • Humans
  • Hypothyroidism / metabolism*
  • Insulin Resistance
  • Metabolic Syndrome / metabolism
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Renal Insufficiency, Chronic / metabolism
  • Risk Factors
  • Thyroid Gland / metabolism*
  • Thyrotropin / metabolism*
  • Thyroxine / metabolism*
  • Triglycerides / metabolism


  • Cholesterol, LDL
  • Triglycerides
  • Thyrotropin
  • Thyroxine