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

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 9; pp. e3355 - e3362
• Main Authors: van der Boom, Trynke, Jia, Congzhuo, Lefrandt, Joop D, Connelly, Margery A, Links, Thera P, Tietge, Uwe J F, Dullaart, Robin P F
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-09-2020
• Subjects: Adult; Apolipoprotein A; Apolipoprotein A-I; Apolipoprotein B; Apolipoproteins; Blood cholesterol; Cholesterol; Cholesterol, HDL - blood; Cholesterol, HDL - metabolism; Clinical s; Ethylenediaminetetraacetic acid; Female; High density lipoprotein; Hormone Replacement Therapy; Humans; Hypothyroidism; Hypothyroidism - complications; Hypothyroidism - drug therapy; Hypothyroidism - metabolism; Hypothyroidism - pathology; Lipid metabolism; Lipid Metabolism Disorders - blood; Lipid Metabolism Disorders - drug therapy; Lipid Metabolism Disorders - etiology; Lipid Metabolism Disorders - metabolism; Lipoproteins; Low density lipoproteins; Macrophages; Male; Medicin och hälsovetenskap; Middle Aged; Netherlands; NMR; Nuclear magnetic resonance; Oxidation; Physiological aspects; Registries; Severity of Illness Index; Supplements; Thyroid carcinoma; Thyroid gland; Thyroid hormones; Thyroid Hormones - therapeutic use; Thyroid-stimulating hormone; Thyroidectomy; Thyrotropin - blood; Time Factors; Treatment Outcome; Netherlands; HDL subfractions; cholesterol efflux capacity; hypothyroidism; nuclear magnetic resonance; HDL ant-oxidative capacity; HDL cholesterol
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa411

Abstract
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.