INCREASED OXIDIZABILITY OF LOW-DENSITY LIPOPROTEINS IN HYPOTHYROIDISM

Hypothyroidism leads to an increase of plasma low-density lipoprotein (LDL) cholesterol levels. Oxidation of LDL particles changes their int rinsic propel ties, thereby enhancing the development of atheroscleros is. T-4 has three specific binding sites on apolipoprotein B; furtherm ore it inhibits LDL oxidation in vitro. We therefore hypothesized that T-4 deficiency not only results in elevated LDL-cholesterol levels bu t also in increased LDL oxidation. Ten patients with overt hypothyroid ism were studied when untreated (TSH 76 +/- 13 mU/L, T-4 40 +/- 6 nmol /L) and again when they were euthyroid for at least 3 months during T- 4 treatment (TSH 2.7 +/- 0.5 mU/L, T-4 115 +/- 11 nmol/L). Plasma lipi ds and lipoproteins and the oxidizability and chemical composition of LDL were determined. The transition from the hypothyroid to the euthyr oid state was associated with a decrease (mean +/- SD) of plasma total cholesterol (5.8 +/- 0.3 vs. 4.8 +/- 0.2 mmol/L, P < 0.005), LDL chol esterol (3.8 +/- 0.3 vs. 2.9 +/- 0.2 nmol/L, P < 0.005) and apolipopro tein B (1.2 +/- 0.1 vs. 0.9 +/- 0.1 g/L, P < 0.005); plasma high-densi ty lipoprotein cholesterol, apolipoprotein A-1, and triglycerides did not change. The actual content of dienes in LDL particles was increase d in hypothyroidism, with a decrease after T-4 suppletion [median (ran ge) = 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 T-4 treatment [29 (19-90) vs. 77 (42-96) min, P < 0.0 05; reference range 67-87]. The density, the relative fatty acid conte nt, and the vitamin E content of LDL particles did not change. In conc lusion, the hypothyroid state is not only associated with a quantitati ve increase of LDL particles, but it also changes their quality by inc reasing LDL oxidizability.