This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Diekman, T. Articles by Wiersinga, W. M. Search for Related Content PubMed PubMed Citation Articles by Diekman, T. Articles by Wiersinga, W. M.

Increased Oxidizability of Low-Density Lipoproteins in Hypothyroidism

Departments of Endocrinology (T.D., W.M.W.) and Vascular Medicine (J.J.P.K.), Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam Zuidoost, The Netherlands; and Department of Medicine (P.N.M.D., A.F.H.S.), Division of General Internal Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Theo Diekman, Department of Endocrinology, University of Amsterdam, F5–171, Meibergdreef 9, Amsterdam Zuidoost, The Netherlands 1105 AZ. E-mail: w.m.wiersinga{at}amc.uva.nl

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.

This article has been cited by other articles:

				E. N. Pearce, P. W. F. Wilson, Q. Yang, R. S. Vasan, and L. E. Braverman Thyroid Function and Lipid Subparticle Sizes in Patients with Short-Term Hypothyroidism and a Population-Based Cohort J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 888 - 894. [Abstract] [Full Text] [PDF]

				A. Roos, S. J. L. Bakker, T. P. Links, R. O. B. Gans, and B. H. R. Wolffenbuttel Thyroid Function Is Associated with Components of the Metabolic Syndrome in Euthyroid Subjects J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 491 - 496. [Abstract] [Full Text] [PDF]

				A. Roos, S. P. Linn-Rasker, R. T. van Domburg, J. P. Tijssen, and A. Berghout The Starting Dose of Levothyroxine in Primary Hypothyroidism Treatment: A Prospective, Randomized, Double-blind Trial Arch Intern Med, August 8, 2005; 165(15): 1714 - 1720. [Abstract] [Full Text] [PDF]

				A. R. Cappola and P. W. Ladenson Hypothyroidism and Atherosclerosis J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2438 - 2444. [Full Text] [PDF]

				T. B. Twickler, M. J. M. Cramer, G. M. Dallinga-Thie, M. J. Chapman, D. W. Erkelens, and H. P. F. Koppeschaar Adult-Onset Growth Hormone Deficiency: Relation of Postprandial Dyslipidemia to Premature Atherosclerosis J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2479 - 2488. [Full Text] [PDF]

				B. Biondi, E. A. Palmieri, G. Lombardi, and S. Fazio Effects of Subclinical Thyroid Dysfunction on the Heart Ann Intern Med, December 3, 2002; 137(11): 904 - 914. [Abstract] [Full Text] [PDF]