HDL Cholesterol Efflux Capacity is Impaired in Severe Short-Term Hypothyroidism Despite Increased HDL Cholesterol

Context: Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown.

Objective: To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity.

Design: Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228).

Setting: University hospital setting in The Netherlands.

Patients: Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma.

Main outcome measures: HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation).

Results: During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P = 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P <0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P <0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change.

Conclusion: During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.