The Effect of Thyroid Disorders on Lipid Levels and Metabolism

Medical Clinics of North America

Volumn 96, Issue 2, 2012, Pages 269-281

  Duntas, Leonidas H ^a   Brenta, Gabriela ^b  

^a UNIVERSITY OF ATHENS   (Greece)

^b Dr César Milstein Hospital ^*  (Argentina)

Author keywords

Cholesterol; Hyperthyroidism; Hypothyroidism; Lipids; Thyroid; TSH

Indexed keywords

APOLIPOPROTEIN A5; ARYLDIALKYLPHOSPHATASE 1; EPROTIROME; HIGH DENSITY LIPOPROTEIN; INTERMEDIATE DENSITY LIPOPROTEIN; LEVOTHYROXINE; PLACEBO; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; THYROID HORMONE; THYROMIMETIC AGENT; VERY LOW DENSITY LIPOPROTEIN;

CARDIOVASCULAR RISK; CHOLESTEROL METABOLISM; CHOLESTEROL TRANSPORT; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPOTHYROIDISM; LIPID METABOLISM; LIPOLYSIS; LIPOPROTEIN METABOLISM; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVERSE CHOLESTEROL TRANSPORT; REVIEW; SUBCLINICAL HYPOTHYROIDISM; THYROID DISEASE;

CHOLESTEROL; CHOLESTEROL, LDL; CORONARY DISEASE; HUMANS; HYPOTHYROIDISM; LIPID METABOLISM; LIPOPROTEINS, HDL; MOLECULAR MIMICRY; RISK FACTORS; THYROID DISEASES; THYROID HORMONES; THYROTROPIN; THYROXINE; TRIGLYCERIDES;

EID: 84858778749     PISSN: 00257125     EISSN: 15579859     Source Type: Journal    
DOI: 10.1016/j.mcna.2012.01.012     Document Type: Review

References (98)

1. Von Noorden C.H. Die fettsucht 1900, Wien.
2. Luden G. Collected papers of Mayo Clinic. Mayo Clin Proc 1918, 10:482-487.
3. Epstein A.A., Lande H. Studies on blood lipoids: I. The relation of cholesterol and protein deficiency to basal metabolism. Arch Intern Med 1922, 30:563-577.
4. Mason R.L., Hunt H.M., Hurxthal L. Blood cholesterol values in hyperthyroidism and hypothyroidism-their significance. N Engl J Med 1930, 203:1273-1278.
5. Friedland I.B. Investigations on the influence of thyroid preparations on experimental hypercholesterolemia and athereosclerosis. Zeitung Ges Exp Med 1933, 87:683-689.
6. Loeb J.N. Metabolic changes in hypothyroidism. Werner and Ingbar's the thyroid 1996, 858-863. Lippincott-Raven, Philadelphia. 7th edition. L.E. Braverman, R.D. Utiger (Eds.).
7. Steinberg A.D. Myxedema and coronary artery disease. A comparative autopsy study. Ann Intern Med 1968, 68:338-344.
8. Tagami T., Kimura H., Ohtani S., et al. Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia. Endocr J 2001, 58:449-457.
9. Walton K.W., Scott P.J., Dykes P.W., et al. The significance of alterations in serum lipids in thyroid dysfunction. II. Alterations of the metabolism and turnover of 131-I-low-density lipoproteins in hypothyroidism and thyrotoxicosis. Clin Sci 1965, 29:217-238.
10. Riis A.L., Gravholt C.H. Elevated regional lipolysis in hyperthyroidism. J Clin Endocrinol Metab 2002, 87:4747-4753.
11. Duntas L.H. Changes in lipid profile in overt and subclinical hypothyroidism. The thyroid and cardiovascular risk 2005, 37-44. Georg Thieme Verlag, Stuttgart (Germany). K.M. Derwahl, L.H. Duntas, S. Butz (Eds.).
12. Espenshade P.J., Hughes A.L. Regulation of sterol synthesis in eukaryotes. Annu Rev Genet 2007, 41:401-427.
13. Grifflin A., Zampelas A. Influence of dietary fatty acids on the atherogenic lipoprotein phenotype. Nutr Res Rev 1995, 8:1-26.
14. Angles-Cano E., de la Pena Diaz A., Loyau S. Inhibition of fibrinolysis by lipoprotein (a). Ann N Y Acad Sci 2001, 936:261-275.
15. Duntas L. Thyroid disease and lipids. Thyroid 2002, 12:287-293.
16. Abrams J.J., Grundy S.M. Cholesterol metabolism in hypothyroidism and hyperthyroidism in man. J Lipid Res 1981, 22:323-338.
17. 3 in the degradation of LDL by cultured human skin fibroblast. J Clin Endocrinol Metab 1979, 48:887-889.
18. Staels B., Van Tol A., Chan L., et al. Alterations in thyroid status modulate apolipoprotein, hepatic triglyceride lipase, and low density lipoprotein receptor in rats. Endocrinology 1990, 127:1144-1152.
19. Salter A.M., Hayashi R., al-Seeni M., et al. Effects of hypothyroidism and high-fat feeding on mRNA concentrations for the low-density-lipoprotein receptor and on acyl-CoA:cholesterol acyltransferase activities in rat liver. Biochem J 1991, 276:825-832.
20. Weber L.W., Boll M., Stampfl A. Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins. World J Gastroenterol 2004, 10:3081-3087.
21. Bakker O., Hudig F., Meijssen S., et al. Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene. Biochem Biophys Res Commun 1998, 249:517-522.
22. Ness G., Lopez D., Chambers C., et al. Effects of L-triiodothyronine and the thyromimetic L-94091 on serum lipoprotein levels and hepatic low density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and apo A-I gene expression. Biochem Pharmacol 1998, 56:121-129.
23. Choi J., Choi H. The regulatory effects of thyroid hormone on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Endocr Res 2000, 26:1-21.
24. Valdemarsson S., Nilsson-Ehle P. Hepatic lipase and the clearing reaction: studies in euthyroid and hypothyroid subjects. Horm Metab Res 1987, 19:28-30.
25. Lithell H., Boberg J., Hellsing K., et al. Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. Eur J Clin Invest 1981, 11:3-10.
26. Kussi T., Taskinen M.R., Nikkila E.A. Lipoproteins, lipolytic enzymes, and hormonal status in hypothyroid women at different levels of substitution. J Clin Endocrinol Metab 1988, 66:61-66.
27. Tan K., Shiu S., Kung A. Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein. J Clin Endocrinol Metab 1998, 83:2921-2924.
28. Ridgway N.D., Dolphin P.J. Serum activity and hepatic secretion of lecithin:cholesterol acyltransferase in experimental hypothyroidism and hypercholesterolemia. J Lipid Res 1985, 26:1300-1313.
29. Benvenga S., Robbins J. Altered thyroid hormone binding to plasma lipoproteins in hypothyroidism. Thyroid 1996, 6:3377-3378.
30. Shin D.J., Osborne T.F. Thyroid hormone regulation and cholesterol metabolism are connected through sterol regulatory element-binding protein-2 (SREBP-2). J Biol Chem 2003, 278:34114-34118.
31. Johansson L., Puding M., Scanlan T.S., et al. Selective thyroid receptor modulation by GC-1 reduces lipids and stimulates steps of reverse cholesterol transport in euthyroid mice. Proc Natl Acad Sci U S A 2005, 102:10297-10302.
32. Day R., Gebhard R.L., Schwartz H.L., et al. Time course of hepatic HMG-CoA reductase activity and mRNA, biliary lipid secretion, and hepatic cholesterol content in methimazole-treated hypothyroid and hypophysectomized rats after triiodothyronine administration: possible linkage of cholesterol synthesis to biliary secretion. Endocrinology 1989, 125:459-468.
33. Ockenga J, Valentini L, Schuetz T, et al. Plasma bile acids are associated with energy expenditure and thyroid function in humans. J Clin Endocrinol Metab, in press.
34. Iizuka K., Horikawa Y. ChREBP: a glucose activated transcription factor. Endocr J 2008, 55:617-624.
35. Hashimoto K., Ishida E., Matsumoto S., et al. Carbohydrate response element binding protein gene expression is positively regulated by thyroid hormone. Endocrinology 2009, 150:3417-3424.
36. Gauthier K., Billon C., Bissler M., et al. Thyroid hormone receptor beta (TRbeta) and liver X receptor (LXR) regulate carbohydrate-response element-binding protein (ChREBP) expression in a tissue-selective manner. J Biol Chem 2010, 285:28156-28163.
37. Prieur X., Huby T., Coste H., et al. Thyroid hormone regulates the hypotriglyceridemic gene APOA5. J Biol Chem 2005, 280:27533-27543.
38. Verdugo C., Perrot L., Ponsin G., et al. Time-course of alterations of high density lipoproteins (HDL) during thyroxine administration to hypothyroid women. Eur J Clin Invest 1987, 17:313-316.
39. O'Brien T., Dinneen S.F., O'Brien P.C., et al. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc 1993, 68:860-866.
40. Doi H., Kugiyama K., Oka H., et al. Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism. Circulation 2000, 102:670-676.
41. Duntas L., Mantzou E., Koutras D.A. Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism. Thyroid 2002, 12:1003-1007.
42. Efrat M., Aviram M. Paraoxonase 1 interactions with HDL, antioxidants and macrophages regulate atherogenesis: a protective role for HDL phospholipids. Adv Exp Med Biol 2010, 660:153-166.
43. Azizi F., Raiszadeh F., Solati M., et al. Serum paraoxonase 1 activity is decreased in thyroid dysfunction. J Endocrinol Invest 2003, 26:703-709.
44. Abbas J.M., Chakraborty J., Akanji A.O., et al. Hypothyroidism results in small dense LDL independent of IRS and traits hypertriglyceridemia. Endocr J 2008, 55:381-389.
45. Roscini A.R., Lupattelli G., Siepi D., et al. Low density lipoprotein size in primary hypothyroidism. Effects of hormone replacement therapy. Ann Nutr Metab 1999, 43:374-379.
46. Pearce E.N., Wilson P.W., Yang Q., et al. Thyroid function and lipid subparticle in patients with short-term hypothyroidism and sizes a population-based cohort. J Clin Endocrinol Metab 2008, 93:888-894.
47. Kim C.S., Kang J.G., Lee S.J., et al. Relationship of low-density lipoprotein (LDL) particle size to thyroid function status in Koreans. Clin Endocrinol (Oxf) 2009, 71:130-136.
48. Rana JS, Boekholdt S, Kastelein JJ, et al. The role of non-HDL-cholesterol in risk stratification for coronary artery disease. Curr Atheroscler Rep, in press.
49. Ito M., Takamatsu J., Sasaki I., et al. Disturbed metabolism of remnant lipoproteins in patients with subclinical hypothyroidism. Am J Med 2004, 117:696-699.
50. Ito M., Arishima T., Kudo T., et al. Effect of levothyroxine replacement on non-high density lipoprotein cholesterol in hypothyroid patients. J Clin Endocrinol Metab 2007, 92:608-611.
51. Kutty K.M., Bryant D.G., Farid N.R. Serum lipids in hypothyroidism - a re-evaluation. J Clin Endocrinol Metab 1978, 46:55-56.
52. Ridgway E.C., Cooper D.S., Walker H., et al. Peripheral responses to thyroid hormone before and after l-thyroxine therapy in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1981, 53:1238-1242.
53. Staub J.J., Althaus B.U., Engler H., et al. Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. Am J Med 1992, 92:631-642.
54. Pearce EN. Update in lipid alterations in subclinical hypothyroidism. J Clin Endocrinol Metab, in press.
55. Canaris G.J., Manowitz N.R., Mayor G., et al. The Colorado thyroid disease prevalence study. Arch Intern Med 2000, 160:526-534.
56. Vierhapper H., Nardi A., Grosser P., et al. Low-density lipoprotein cholesterol in subclinical hypothyroidism. Thyroid 2000, 10:981-984.
57. Hueston W.J., Pearson W. Subclinical hypothyroidism and the risk of hypercholesterolemia. Ann Fam Med 2004, 2:351-355.
58. Bindels A., Westendorp R., Frolich M., et al. The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding?. Clin Endocrinol 1999, 50:217-220.
59. Leclère J., Cousty C., Schlienger J.L., et al. Subclinical hypothyroidism and quality of life of women aged 50 or more with hypercholesterolemia: results of the HYOGA study. Presse Med 2008, 37:1538-1546.
60. Mueller B., Zulewski H., Huber P., et al. Impaired action of thyroid hormone associated with smoking in women with hypothyroidism. N Engl J Med 1995, 333:964-969.
61. Bakker S., ter Maaten J.C., Popp-Snijders C., et al. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab 2001, 86:1206-1211.
62. Chubb S.A., Davis W.A., Davis T.M. Interactions among thyroid function, insulin sensitivity, and serum lipid concentrations: the fremantle diabetes study. J Clin Endocrinol Metab 2005, 90:5317-5320.
63. Brenta G., Berg G., Arias P., et al. Lipoprotein alterations, insulin sensitivity and hepatic lipase activity in Lipoprotein subclinical hypothyroidism (sH). Response to treatment with L-T4. Thyroid 2007, 17:453-460.
64. Brenta G., Berg G., Arias P., et al. Proatherogenic mechanisms in subclinical hypothyroidism: hepatic lipase activity in relation to the VLDL remnant IDL. Thyroid 2008, 18:1233-1236.
65. Sigal G.A., Medeiros-Neto G., Vinagre J.C., et al. Lipid metabolism in subclinical hypothyroidism: plasma kinetics of triglyceride-rich lipoproteins and lipid transfers to high-density lipoprotein before and after levothyroxine treatment. Thyroid 2011, 21:347-353.
66. Danese M.D., Ladenson P.W., Meinert C.L., et al. Clinical review 115: effect of thyroxin therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab 2000, 85:2993-3001.
67. Meier C., Straub J.J., Roth C.B., et al. TSH-controlled L-thyroxine therapy reduces cholesterol level and clinical symptoms in subclinical hypothyroidism: a double-blind, placebo-controlled trial (Basel Thyroid Study). J Clin Endocrinol Metab 2001, 86:4860-4866.
68. Carraccio N., Ferrannini E., Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement a randomized placebo-controlled study. J Endocrinol Metab 2007, 87:1533-1538.
69. Taddei S., Caraccio N., Virdis A., et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab 2003, 88:3731-3737.
70. Michalopoulou G., Alevizaki M., Piperingos G., et al. High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?. Eur J Endocrinol 1998, 138:141-145.
71. Iqbal A., Jorde R., Figenschau Y. Serum lipid levels in relation to serum thyroid-stimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism: the Tromsø Study. J Intern Med 2006, 260:53-61.
72. Asvold B.O., Vatten L.J., Nilsen T.I., et al. The association between the TSH within the reference range and serum lipid concentrations in a population- based study: the HUNT study. Eur J Endocrinol 2007, 156:181-186.
73. Razvi S., Ingoe L., Keeka G., et al. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab 2007, 92:1715-1723.
74. Teixeira P.F., Reuters V.S., Ferreira M.M., et al. Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial. Horm Metab Res 2008, 40:50-55.
75. Biondi B., Cooper D.S. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008, 29:76-131.
76. Vanderpump M.P., Tunbridge W.M., French J.M., et al. The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20 year follow-up study of an English community. Thyroid 1996, 6:155-160.
77. Hak A.E., Pols H.A., Visser T.J., et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infraction in elderly women: the Rotterdam Study. Ann Intern Med 2000, 132:270-278.
78. Klein I., Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001, 344:501-509.
79. Cappola A., Ladenson P. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 2003, 88:2438-2444.
80. Steinberg D., Parthasarathy S., Carew T., et al. Beyond cholesterol: modifications of low density lipoprotein that increase its atherogenicity. N Engl J Med 1989, 320:915-924.
81. Rizos C.V., Elisaf M.S., Liberopoulos E.N. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J 2011, 5:76-84.
82. Biondi B., Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine 2004, 24:1-13.
83. Rodondi N., Aujesky D., Vittinghoff E., et al. Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Am J Med 2006, 119:541-551.
84. Duntas L.H., Wartofsky L. Cardiovascular risk and subclinical hypothyroidism: focus on lipids and new emerging risk factors. What is the evidence?. Thyroid 2007, 17:1075-1084.
85. Rotondi N., den Elzen W.P., Bauer D.C., et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010, 304:1365-1374.
86. Raziel A., Rosenzweig B., Botvinic V., et al. The influence of thyroid function on serum lipid profile. Atherosclerosis 1982, 41:321-326.
87. Heimberg M., Olubadewo J.O., Wilcox H.G. Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states. Endocr Rev 1985, 6:590-607.
88. Sundaram V., Hanna A., Koneru L., et al. Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation. J Clin Endocrinol Metab 1997, 82:3421-3424.
89. Yavuz D.G., Yüksel M., Deyneli O., et al. Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients. Clin Endocrinol (Oxf) 2004, 6:515-521.
90. Beylot M., Martin C., Laville M., et al. Lipolytic and ketogenic flux in hyperthyroidism. J Clin Endocrinol Metab 1991, 73:42-49.
91. Hagenfeldt L., Wennlund A., Felig P., et al. Turnover and splanchnic metabolism of free fatty acids in hyperthyroid patients. J Clin Invest 1981, 67:1672-1677.
92. Cachefo A., Boucher P., Vidon C., et al. Hepatic lipogenesis and cholesterol synthesis in hyperthyroid patients. J Clin Endocrinol Metab 2001, 86:5353-5357.
93. Nishitani H., Okamura K., Noguchi S., et al. Serum lipid levels in thyroid dysfunction with special reference to transient elevation during treatment in hyperthyroid Graves' disease. Horm Metab Res 1990, 22:490-493.
94. Diekman M.J., Anghelescu N., Endert E., et al. Changes in plasma low-density lipoprotein (LDL)-and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes. J Clin Endocrinol Metab 2000, 85:1857-1862.
95. Scanlan T. Thyroid hormone analogues: useful biological probes and potential therapeutic agents. Ann Endocrinol 2008, 69:157-159.
96. Trancevski I., Eller P., Patsch J.R., et al. The resurgence of thyromimetics as lipid-modifying agents. Curr Opin Investig Drugs 2009, 10:912-918.
97. Trancevski I., Demetz E., Eller P. Sobetirome: a selective thyromimetic for the treatment of dyslipidemia. Recent Pat Cardiovasc Drug Discov 2011, 6:16.
98. Ladenson P.W., Kristensen J.D., Ridgway E.C., et al. Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N Engl J Med 2010, 362:906-916.