Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels have a causal relationship with blood lipids, according to the results of a statistical analysis published in Endocrinology.

Though observational studies using Mendelian randomization (MR) have demonstrated a causal relationship between normal range TSH levels and blood lipids, a causal relationship between FT4 and lipids has not yet been performed and previous studies included data that could compromise MR and did not rule out the possibility of reverse causation.

To determine if there is a causal relationship between thyroid function and blood lipid profiles, data from the ThyroidOmics Consortium of 22 independent cohorts with 54,288 individuals for the TSH, and from 19 cohorts with 49,269 individuals for FT4 were analyzed. Data was also included from the Global Lipids Genetics Consortium which included 188,577 individuals.A two-sample bi-directional MR analysis as well as multi-model analytics and various sensitivity analyses were conducted.

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A one standard deviation (SD) increase in TSH levels was found to be causally associated with a 0.048 SD increase in total cholesterol (TC) (P <.001) and a 0.032 SD increase in low-density lipoprotein cholesterol (LDL) (P =.021). A one SD increase in FT4 levels was found to be causally associated with a 0.056 SD decrease in TC (P =.014), and a 0.072 SD decrease in LDL (P =.009). No significant association between TSH or FT4 and high-density lipoprotein cholesterol (HDL) or triglycerides (TG) was found.

The results of this study established a causal relationship between thyroid function biomarkers and cholesterol levels. Though previous studies have shown an association between TSH and blood lipids, the data analysis was compromised and could not definitively establish a causal relationship or the impact of FT4.

Limitations to this study include the exclusion of individuals of non-European ancestry, making the results difficult to apply to other populations, though genetic homogeneity is required for MR analysis. Additionally, data from various individuals were analyzed.

Future research addressing this relationship in other ethnicities is warranted.




Wang Y, Guo P, Liu L, Zhang Y, Zeng P, Yuan Z. Mendelian randomization highlights the causal role of normal thyroid function on blood lipid profiles. Endocrinology. 2021;162(5):bqab037. doi:10.1210/endocr/bqab037