Increased oxidizability of low-density lipoproteins in hypothyroidism

• Published in: The journal of clinical endocrinology and metabolism Vol. 83; no. 5; pp. 1752 - 1755
• Main Authors: DIEKMAN, T, DEMACKER, P. N. M, KASTELEIN, J. J. P, STALENHOEF, A. F. H, WIERSINGA, W. M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-05-1998
• Subjects: Adult; Aged; Apolipoproteins B - blood; Biological and medical sciences; Cholesterol - blood; Cholesterol, LDL - blood; Endocrinopathies; Female; Humans; Hypothyroidism - blood; Hypothyroidism - drug therapy; Kinetics; Lipids - blood; Lipoproteins - blood; Lipoproteins, LDL - analysis; Lipoproteins, LDL - blood; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oxidation-Reduction; Thyroid. Thyroid axis (diseases); Thyrotropin - blood; Thyroxine - blood; Thyroxine - therapeutic use; Triiodothyronine - blood; Endocrinopathy; Human; Lipoprotein LDL; Chemotherapy; Replacement therapy; Oxidized state; Pathophysiology; Thyroid diseases; Oxidation; Chemical properties; Hypothyroidism; Comparative study
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.83.5.1752

Hypothyroidism leads to an increase of plasma low-density lipoprotein (LDL) cholesterol levels. Oxidation of LDL particles changes their intrinsic properties, thereby enhancing the development of atherosclerosis. T4 has three specific binding sites on apolipoprotein B; furthermore it inhibits LDL oxidation in vitro. We therefore hypothesized that T4 deficiency not only results in elevated LDL-cholesterol levels but also in increased LDL oxidation. Ten patients with overt hypothyroidism were studied when untreated (TSH 76 +/- 13 mU/L, T4 40 +/- 6 nmol/L) and again when they were euthyroid for at least 3 months during T4 treatment (TSH 2.7 +/- 0.5 mU/L, T4 115 +/- 11 nmol/L). Plasma lipids and lipoproteins and the oxidizability and chemical composition of LDL were determined. The transition from the hypothyroid to the euthyroid state was associated with a decrease (mean +/- SE) of plasma total cholesterol (5.8 +/- 0.3 vs. 4.8 +/- 0.2 mmol/L, P < 0.005), LDL cholesterol (3.8 +/- 0.3 vs. 2.9 +/- 0.2 nmol/L, P < 0.005) and apolipoprotein B (1.2 +/- 0.1 vs. 0.9 +/- 0.1 g/L, P < 0.005); plasma high-density lipoprotein cholesterol, apolipoprotein A-1, and triglycerides did not change. The actual content of dienes in LDL particles was increased in hypothyroidism, with a decrease after T4 suppletion [median (range) = 257 (165-346) vs. 188 (138-254) nmol/mg LDL protein, P < 0.005; reference range 140-180]. The lag time, an estimate of the resistance of LDL against oxidation in vitro, was shortened when hypothyroid but normalized after T4 treatment [29 (19-90) vs. 77 (42-96) min, P < 0.005; reference range 67-87]. The density, the relative fatty acid content, and the vitamin E content of LDL particles did not change. In conclusion, the hypothyroid state is not only associated with a quantitative increase of LDL particles, but it also changes their quality by increasing LDL oxidizability.