High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) may be impaired in patients with severe short-term hypothyroidism, according to the results of an observational study published in the Journal of Clinical Endocrinology & Metabolism.

Hypothyroidism is associated with an increase in low-density lipoprotein (LDL) cholesterol, plasma lipoprotein (a), and proprotein convertase subtilisin/kexin type 9. In severe hypothyroidism, HDL cholesterol and triglycerides levels are also elevated. However, the effects of severe hypothyroidism on HDL function are not clearly understood. 

The aim of the current study was to assess the impact of severe short-term hypothyroidism on HDL function, CEC, and HDL anti-oxidative capacity.

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In this study, 17 patients (median age, 46 years; 16 women) who had undergone total thyroidectomy for thyroid cancer were enrolled. In this cohort, the median thyroid stimulating hormone (TSH) level was 81.9 mU/L and free thyroxin was 2.3 pmol/L. During thyroid hormone supplementation, TSH was reduced to 0.03 mU/L.

Thyroid hormone supplementation resulted in marked reductions in plasma total cholesterol, LDL cholesterol, non-HDL cholesterol, and triglycerides, compared with values before supplementation.  

While HDL cholesterol levels were reduced by thyroid hormone supplementation, there was no change in the total HDL particle concentration. HDL size —  calculated using weighted averages derived from the sum of the diameters of each subclass (small, medium, and large) multiplied by its relative mass percentage — was found to have shifted from large- to more medium-sized HDL particles in response to thyroid hormone supplementation.

An increase in CEC was detected during thyroid hormone supplementation, and maintained after correcting for HDL cholesterol or HDL particle concentration. The anti-oxidant function of HDL was not affected by treatment with thyroid hormone.

Study limitations include the relatively small sample size, and lack of a control group.

“In view of the inverse associations of CEC, as well as of the HDL particle concentration with [atherosclerotic cardiovascular disease], we surmise that the increase in HDL cholesterol does not sufficiently counteract the deleterious effects of LDL cholesterol elevations and other pro-atherogenic biomarkers on overt hypothyroidism-related [atherosclerotic cardiovascular disease] risk,” noted the researchers.


van der Boom T, Jia C, Lefrandt JD, et al. HDL cholesterol efflux capacity is impaired in severe short-term hypothyroidism despite increased HDL cholesterol. J Clin Endocrinol Metab. 2020;105(9):dgaa411. doi:10.1210/clinem/dgaa411