Dyslipidemia is a common finding in patients with thyroid disease, explained by the adverse effects of thyroid hormones in almost all steps of lipid metabolism. Not only overt but also subclinical hypo- and hyperthyroidism, through different mechanisms, are associated with lipid alterations, mainly concerning total and LDL cholesterol and less often HDL cholesterol, triglycerides, lipoprotein (a), apolipoprotein A1, and apolipoprotein B. In addition to quantitative, qualitative alterations of lipids have been also reported, including atherogenic and oxidized LDL and HDL particles. In thyroid disease, dyslipidemia coexists with various metabolic abnormalities and induce insulin resistance and oxidative stress via a vice-vicious cycle. The above associations in combination with the thyroid hormone induced hemodynamic alterations, might explain the increased risk of coronary artery disease, cerebral ischemia risk, and angina pectoris in older, and possibly ischemic stroke in younger patients with overt or subclinical hyperthyroidism. 1. Introduction Thyroid disease, namely hypothyroidism and hyperthyroidism, constitutes the most common endocrine abnormality in recent years, diagnosed either in subclinical or clinical form. According to the 6-year duration NHANES III Study, the prevalence of hypothyroidism was 4.6% (0.3% clinical and 4.3% subclinical) and of hyperthyroidism 1.3% (0.5% clinical and 0.7% subclinical), in population aged at least 12 years, showing an age and sex dependence [1]. Thyroid disease is associated with various metabolic abnormalities, due to the effects of thyroid hormones on nearly all major metabolic pathways. Thyroid hormones regulate the basal energy expenditure through their effect on protein, carbohydrate, and lipid metabolism. This might be a direct effect or an indirect effect by modification of other regulatory hormones such as insulin or catecholamines [2]. Dyslipidemia is a common metabolic abnormality in patients with thyroid disease, either in the overt or subclinical forms of the disease, and constitutes the end result of the effect of thyroid hormones in all aspects of lipid metabolism leading to various quantitative and/or qualitative changes of triglycerides, phospholipids, cholesterol, and other lipoproteins [3]. In thyroid disease, dyslipidemia and the coexisting metabolic abnormalities, in combination with the thyroid hormone-induced hemodynamic alterations, explain the high risk for cardiovascular disease [4–7]. 2. Effects of Thyroid Hormones on Lipid Metabolism Thyroid hormones influence all aspects of lipid
References
[1]
J. G. Hollowell, N. W. Staehling, W. D. Flanders et al., “Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III),” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 2, pp. 489–499, 2002.
[2]
B. Kim, “Thyroid hormone as a determinant of energy expenditure and the basal metabolic rate,” Thyroid, vol. 18, no. 2, pp. 141–144, 2008.
[3]
X. Zhu and S. Y. Cheng, “New insights into regulation of lipid metabolism by thyroid hormone,” Current Opinion in Endocrinology, Diabetes and Obesity, vol. 17, no. 5, pp. 408–413, 2010.
[4]
B. Biondi and I. Klein, “Hypothyroidism as a risk factor for cardiovascular disease,” Endocrine, vol. 24, no. 1, pp. 1–13, 2004.
[5]
B. Biondi and G. J. Kahaly, “Cardiovascular involvement in patients with different causes of hyperthyroidism,” Nature Reviews Endocrinology, vol. 6, no. 8, pp. 431–443, 2010.
[6]
I. Klein and K. Ojamaa, “Thyroid hormone and the cardiovascular system,” The New England Journal of Medicine, vol. 344, no. 7, pp. 501–509, 2001.
[7]
S. Fazio, E. A. Palmieri, G. Lombardi, and B. Biondi, “Effects of thyroid hormone on the cardiovascular system,” Recent Progress in Hormone Research, vol. 59, pp. 31–50, 2004.
[8]
A. N. A. Cachefo, P. Boucher, C. Vidon, E. Dusserre, F. Diraison, and M. Beylot, “Hepatic lipogenesis and cholesterol synthesis in hyperthyroid patients,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 11, pp. 5353–5357, 2001.
[9]
J. J. Abrams, S. M. Grundy, and H. Ginsberg, “Metabolism of plasma triglycerides in hypothyroidism and hyperthyroidism in man,” Journal of Lipid Research, vol. 22, no. 2, pp. 307–322, 1981.
[10]
K. S. L. Lam, M. K. Chan, and R. T. T. Yeung, “High-density lipoprotein cholesterol, hepatic lipase and lipoprotein lipase activities in thyroid dysfunction—effects of treatment,” Quarterly Journal of Medicine, vol. 59, no. 229, pp. 513–521, 1986.
[11]
R. M. Krauss, R. I. Levy, and D. S. Fredrickson, “Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia,” Journal of Clinical Investigation, vol. 54, no. 5, pp. 1107–1124, 1974.
[12]
K. C. B. Tan, S. W. M. Shiu, and A. W. C. Kung, “Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 8, pp. 2921–2924, 1998.
[13]
M. Heimberg, J. O. Olubadewo, and H. G. Wilcox, “Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states,” Endocrine Reviews, vol. 6, no. 4, pp. 590–607, 1985.
[14]
Y. Y. Liu and G. A. Brent, “Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation,” Trends in Endocrinology and Metabolism, vol. 21, no. 3, pp. 166–173, 2010.
[15]
J. A. Berti, M. E. C. Amaral, A. C. Boschero et al., “Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice,” Metabolism, vol. 50, no. 5, pp. 530–536, 2001.
[16]
I. Tancevski, A. Wehinger, E. Demetz et al., “Reduced plasma high-density lipoprotein cholesterol in hyperthyroid mice coincides with decreased hepatic adenosine 5′-triphosphate-binding cassette transporter 1 expression,” Endocrinology, vol. 149, no. 7, pp. 3708–3712, 2008.
[17]
G. Sauter, M. Weiss, and R. Hoermann, “Cholesterol 7α-hydroxylase activity in hypothyroidism and hyperthyroidism in humans,” Hormone and Metabolic Research, vol. 29, no. 4, pp. 176–179, 1997.
[18]
V. A. B. Drover and L. B. Agellon, “Regulation of the human cholesterol 7α-hydroxylase gene (CYP7A1) by thyroid hormone in transgenic mice,” Endocrinology, vol. 145, no. 2, pp. 574–581, 2004.
[19]
A. Santi, M. M. M. F. Duarte, R. N. Moresco et al., “Association between thyroid hormones, lipids and oxidative stress biomarkers in overt hypothyroidism,” Clinical Chemistry and Laboratory Medicine, vol. 48, no. 11, pp. 1635–1639, 2010.
[20]
N. Nanda, Z. Bobby, and A. Hamide, “Association of thyroid stimulating hormone and coronary lipid risk factors with lipid peroxidation in hypothyroidism,” Clinical Chemistry and Laboratory Medicine, vol. 46, no. 5, pp. 674–679, 2008.
[21]
D. G. Yavuz, M. Yüksel, O. Deyneli, Y. Ozen, H. Aydin, and S. Akalin, “Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients,” Clinical Endocrinology, vol. 61, no. 4, pp. 515–521, 2004.
[22]
V. Sundaram, A. N. Hanna, L. Koneru, H. A. I. Newman, and J. M. Falko, “Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 10, pp. 3421–3424, 1997.
[23]
F. Costantini, S. D. Pierdomenico, D. De Cesare et al., “Effect of thyroid function on LDL oxidation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 5, pp. 732–737, 1998.
[24]
T. Diekman, P. N. M. Demacker, J. J. P. Kastelein, A. F. H. Stalenhoef, and W. M. Wiersinga, “Increased oxidizability of low-density lipoproteins in hypothyroidism,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 5, pp. 1752–1755, 1998.
[25]
M. Peppa, C. Koliaki, P. Nikolopoulos, and S. A. Raptis, “Skeletal muscle insulin resistance in endocrine disease,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 527850, 2010.
[26]
E. Maratou, D. J. Hadjidakis, A. Kollias et al., “Studies of insulin resistance in patients with clinical and subclinical hypothyroidism,” European Journal of Endocrinology, vol. 160, no. 5, pp. 785–790, 2009.
[27]
E. Maratou, D. J. Hadjidakis, M. Peppa et al., “Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism,” European Journal of Endocrinology, vol. 163, no. 4, pp. 625–630, 2010.
[28]
T. Tagami, T. Tamanaha, S. Shimazu et al., “Lipid profiles in the untreated patients with Hashimoto thyroiditis and the effects of thyroxine treatment on subclinical hypothyroidism with Hashimoto thyroiditis,” Endocrine Journal, vol. 57, no. 3, pp. 253–258, 2010.
[29]
T. Tzotzas, G. E. Krassas, T. Konstantinidis, and M. Bougoulia, “Changes in lipoprotein(a) levels in overt and subclinical hypothyroidism before and during treatment,” Thyroid, vol. 10, no. 9, pp. 803–808, 2000.
[30]
P. D. F. D. S. Teixeira, V. S. Reuters, M. M. Ferreira et al., “Lipid profile in different degrees of hypothyroidism and effects of levothyroxine replacement in mild thyroid failure,” Translational Research, vol. 151, no. 4, pp. 224–231, 2008.
[31]
T. W. A. de Bruin, H. Van Barlingen, M. Van Linde-Sibenius Trip, A. R. R. Van Vuurst de Vries, M. J. Akveld, and D. W. Erkelens, “Lipoprotein(a) and apolipoprotein B plasma concentrations in hypothyroid, euthyroid, and hyperthyroid subjects,” Journal of Clinical Endocrinology and Metabolism, vol. 76, no. 1, pp. 121–126, 1993.
[32]
A. Raziel, B. Rosenzweig, V. Botvinic, et al., “The influence of thyroid function on serum lipid profile,” Atherosclerosis, vol. 41, no. 2-3, pp. 321–326, 1982.
[33]
J. J. Staub, B. U. Althaus, H. Engler et al., “Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues,” American Journal of Medicine, vol. 92, no. 6, pp. 631–642, 1992.
[34]
R. P. F. Dullaart, J. J. van Doormaal, K. Hoogenberg, and W. J. Sluiter, “Triiodothyronine rapidly lowers plasma lipoprotein (a) in hypothyroid subjects,” Netherlands Journal of Medicine, vol. 46, no. 4, pp. 179–184, 1995.
[35]
A. N. Torun, S. Kulaksizoglu, M. Kulaksizoglu, B. O. Pamuk, E. Isbilen, and N. B. Tutuncu, “Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism,” Clinical Endocrinology, vol. 70, no. 3, pp. 469–474, 2009.
[36]
A. Becerra, D. Bellido, A. Luengo, G. Piédrola, and D. A. De Luis, “Lippprotein(a) and other lipoproteins in hypothyroid patients before and after thyroid replacement therapy,” Clinical Nutrition, vol. 18, no. 5, pp. 319–322, 1999.
[37]
I. C. Klausen, F. E. Nielsen, L. Hegedus, L. U. Gerdes, P. Charles, and O. Faergeman, “Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a),” Metabolism, vol. 41, no. 8, pp. 911–914, 1992.
[38]
M. Ito, T. Arishima, T. Kudo et al., “Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 2, pp. 608–611, 2007.
[39]
M. Paoli, G. Bellabarba, E. Velazquez et al., “Sex steroids, lipids, and lipoprotein cholesterols in women with subclinical and overt hypothyroidism before and after L-thyroxine therapy,” Clinica Chimica Acta, vol. 275, no. 1, pp. 81–91, 1998.
[40]
F. Pazos, J. J. Alvarez, J. Rubies-Prat, C. Varela, and M. A. Lasuncion, “Long term thyroid replacement therapy and levels of lipoprotein(a) and other lipoproteins,” Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 2, pp. 562–566, 1995.
[41]
M. L. Martánez-Triguero, A. Hernández-Mijares, T. T. Nguyen et al., “Effect of thyroid hormone replacement on lipoprotein(a), lipids, and apolipoproteins in subjects with hypothyroidism,” Mayo Clinic Proceedings, vol. 73, no. 9, pp. 837–841, 1998.
[42]
T. O'Brien, K. Katz, D. Hodge, T. T. Nguyen, B. A. Kottke, and I. D. Hay, “The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E,” Clinical Endocrinology, vol. 46, no. 1, pp. 17–20, 1997.
[43]
R. Arem, D. A. Escalante, N. Arem, J. D. Morrisett, and W. Patsch, “Effect of L-thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein(a),” Metabolism, vol. 44, no. 12, pp. 1559–1563, 1995.
[44]
N. Caraccio, E. Ferrannini, and F. Monzani, “Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 4, pp. 1533–1538, 2002.
[45]
F. Monzani, N. Caraccio, M. Kozàkowà et al., “Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 5, pp. 2099–2106, 2004.
[46]
Z. Efstathiadou, S. Bitsis, H. J. Milionis et al., “Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial?” European Journal of Endocrinology, vol. 145, no. 6, pp. 705–710, 2001.
[47]
A. Iqbal, R. Jorde, and Y. Figenschau, “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 Troms？ Study,” Journal of Internal Medicine, vol. 260, no. 1, pp. 53–61, 2006.
[48]
M. Adrees, J. Gibney, N. El-Saeity, and G. Boran, “Effects of 18 months of l-T4 replacement in women with subclinical hypothyroidism,” Clinical Endocrinology, vol. 71, no. 2, pp. 298–303, 2009.
[49]
S. Miura, M. Iitaka, H. Yoshimura et al., “Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy,” Internal Medicine, vol. 33, no. 7, pp. 413–417, 1994.
[50]
A. W. C. Kung, R. W. C. Pang, and E. D. Janus, “Elevated serum lipoprotein(a) in subclinical hypothyroidism,” Clinical Endocrinology, vol. 43, no. 4, pp. 445–449, 1995.
[51]
M. Ito, J. Takamatsu, I. Sasaki et al., “Disturbed metabolism of remnant lipoproteins in patients with subclinical hypothyroidism,” American Journal of Medicine, vol. 117, no. 9, pp. 696–699, 2004.
[52]
E. S. Ganotakis, K. Mandalaki, M. Tampakaki et al., “Subclinical hypothyroidism and lipid abnormalities in older women attending a vascular disease prevention clinic: effect of thyroid replacement therapy,” Angiology, vol. 54, no. 5, pp. 569–576, 2003.
[53]
S. K. Kim, S. H. Kim, K. S. Park, S. W. Park, and Y. W. Cho, “Regression of the increased common carotid artery-intima media thickness in subclinical hypothyroidism after thyroid hormone replacement,” Endocrine Journal, vol. 56, no. 6, pp. 753–758, 2009.
[54]
W. J. Hueston and W. S. Pearson, “Subclinical hypothyroidism and the risk of hypercholesterolemia,” Annals of Family Medicine, vol. 2, no. 4, pp. 351–355, 2004.
[55]
S. K. A. Shakoor, A. Aldibbiat, L. E. Ingoe et al., “Endothelial progenitor cells in subclinical hypothyroidism: the effect of thyroid hormone replacement therapy,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 1, pp. 319–322, 2010.
[56]
R. J. Bell, L. Rivera-Woll, S. L. Davison, D. J. Topliss, S. Donath, and S. R. Davis, “Well-being, health-related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease—a community-based study,” Clinical Endocrinology, vol. 66, no. 4, pp. 548–556, 2007.
[57]
J. Kvetny, P. E. Heldgaard, E. M. Bladbjerg, and J. Gram, “Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years,” Clinical Endocrinology, vol. 61, no. 2, pp. 232–238, 2004.
[58]
M. Yildirimkaya, M. ？zata, K. Yilmaz, C. Kilin？, M. A. Gündo？an, and T. Kutluay, “Lipoprotein(a) Concentration in Subclinical Hypothyroidism before and after Levo-Thyroxine Therapy,” Endocrine Journal, vol. 43, no. 6, pp. 731–736, 1996.
[59]
P. Caron, C. Calazel, H. J. Parra, M. Hoff, and J. P. Louvet, “Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy,” Clinical Endocrinology, vol. 33, no. 4, pp. 519–523, 1990.
[60]
Y. Lai, J. Wang, F. Jiang et al., “The relationship between serum thyrotropin and components of metabolic syndrome,” Endocrine Journal, vol. 58, no. 1, pp. 23–30, 2011.
[61]
H. J. Milionis, Z. Efstathiadou, A. D. Tselepis et al., “Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine,” Thyroid, vol. 13, no. 4, pp. 365–369, 2003.
[62]
G. Rondeau, N. Rutamucero, V. Messier et al., “Reference range thyroid-stimulating hormone is associated with physical activity energy expenditure in overweight and obese postmenopausal women: a Montreal-Ottawa New Emerging Team Study,” Metabolism, vol. 59, no. 11, pp. 1597–1602, 2010.
[63]
G. A. Sigal, G. Medeiros-Neto, J. C. Vinagre, J. Diament, and R. C. Maranh？o, “Lipid metabolism in subclinical hypothyroidism: plasma kinetics of triglyceride-rich lipoproteins and lipid transfers to high-density lipoprotein before and after levothyroxine treatment,” Thyroid, vol. 21, no. 4, pp. 347–353, 2011.
[64]
J. A. Franklyn, J. Daykin, J. Betteridge et al., “Thyroxine replacement therapy and circulating lipid concentrations,” Clinical Endocrinology, vol. 38, no. 5, pp. 453–459, 1993.
[65]
M. Weintraub, I. Grosskopf, Y. Trostanesky, G. Charach, A. Rubinstein, and N. Stern, “Thyroxine replacement therapy enhances clearance of chylomicron remnants in patients with hypothyroidism,” Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 7, pp. 2532–2536, 1999.
[66]
C. Meier, J. J. Staub, C. B. Roth et al., “TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (basel thyroid study),” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 4860–4866, 2001.
[67]
R. Arem and W. Patsch, “Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy,” Archives of Internal Medicine, vol. 150, no. 10, pp. 2097–2100, 1990.
[68]
H. Nishitani, K. Okamura, S. Noguchi, K. Inoue, Y. Morotomi, and M. Fujishima, “Serum lipid levels in thyroid dysfunction with special reference to transient elevation during treatment in hyperthyroid graves' disease,” Hormone and Metabolic Research, vol. 22, no. 9, pp. 490–493, 1990.
[69]
X. Guang-Da, C. Hong-Yan, and Z. Xian-Mei, “Changes in endothelium-dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism,” Clinical Endocrinology, vol. 61, no. 3, pp. 400–404, 2004.
[70]
E. Muls, V. Blaton, and M. Rosseneu, “Serum lipids and apolipoproteins A-I, A-II, and B in hyperthyroidism before and after treatment,” Journal of Clinical Endocrinology and Metabolism, vol. 55, no. 3, pp. 459–464, 1982.
[71]
A. E. Altinova, F. B. T？rüner, M. Aktürk et al., “Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism,” Clinical Endocrinology, vol. 65, no. 4, pp. 530–535, 2006.
[72]
A. W. C. Kung, R. W. C. Pang, I. Lauder, K. S. L. Lam, and E. D. Janus, “Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism,” Clinical Chemistry, vol. 41, no. 2, pp. 226–231, 1995.
[73]
I. C. Klausen, L. Hegedus, P. S. Hansen, F. E. Nielsen, L. U. Gerdes, and O. Faergeman, “Apolipoprotein(a) phonotypes and lipoprotein(a) concentrations in patients with hyperthyroidism,” Journal of Molecular Medicine, vol. 73, no. 1, pp. 41–46, 1995.
[74]
M. Ozata, M. Yildirimkaya, K. Yilmaz et al., “The effects of thyroid status on serum apolipoprotein A-I-containing lipoprotein particles,” Hormone and Metabolic Research, vol. 30, no. 4, pp. 217–221, 1998.
[75]
H. Hayashi, N. Mizushima, H. Yoshinaga et al., “The relationship between lipoprotein(a) and low density lipoprotein receptors during the treatment of hyperthyroidism,” Hormone and Metabolic Research, vol. 28, no. 8, pp. 384–387, 1996.
[76]
F. Hoppichler, C. Sandholzer, R. Moncayo, G. Utermann, and H. G. Georg Kraft, “Thyroid hormone (fT4) reduces lipoprotein(a) plasma levels,” Atherosclerosis, vol. 115, no. 1, pp. 65–71, 1995.
[77]
A. Berghout, J. van de Wetering, and P. Klootwijk, “Cardiac and metabolic effects in patients who present with a multinodular goitre,” Netherlands Journal of Medicine, vol. 61, no. 10, pp. 318–322, 2003.
[78]
J. V. Parle, J. A. Franklyn, K. W. Cross, S. R. Jones, and M. C. Sheppard, “Circulating lipids and minor abnormalities of thyroid function,” Clinical Endocrinology, vol. 37, no. 5, pp. 411–414, 1992.
[79]
B. Biondi, E. A. Palmieri, S. Fazio et al., “Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 12, pp. 4701–4705, 2000.
[80]
V. Kotsis, M. Alevizaki, S. Stabouli et al., “Hypertension and hypothyroidism: results from an ambulatory blood pressure monitoring study,” Journal of Hypertension, vol. 25, no. 5, pp. 993–999, 2007.
[81]
I. Saito, K. Ito, and T. Saruta, “Hypothyroidism as a cause of hypertension,” Hypertension, vol. 5, no. 1, pp. 112–115, 1983.
[82]
O. Mayer, J. ？imon, J. Filipovsky, M. Plá？kova, and R. Pikner, “Hypothyroidism in coronary heart disease and its relation to selected risk factors,” Vascular Health and Risk Management, vol. 2, no. 4, pp. 499–506, 2006.
[83]
M. Christ-Crain, C. Meier, M. Guglielmetti et al., “Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial,” Atherosclerosis, vol. 166, no. 2, pp. 379–386, 2003.
[84]
B. G. Nedreb？, U. B. Ericsson, O. Nyg？rd et al., “Plasma total homocysteine levels in hyperthyroid and hypothyroid patients,” Metabolism, vol. 47, no. 1, pp. 89–93, 1998.
[85]
M. S. Morris, A. G. Bostom, P. F. Jacques, J. Selhub, and I. H. Rosenberg, “Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey,” Atherosclerosis, vol. 155, no. 1, pp. 195–200, 2001.
[86]
A. Squizzato, E. Romualdi, H. R. Büller, and V. E. A. Gerdes, “Clinical review: thyroid dysfunction and effects on coagulation and fibrinolysis: a systematic review,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 7, pp. 2415–2420, 2007.
[87]
C. Erem, “Coagulation and fibrinolysis in thyroid dysfunction,” Endocrine, vol. 36, no. 1, pp. 110–118, 2009.
[88]
R. Chadarevian, E. Bruckert, L. Leenhardt, P. Giral, A. Ankri, and G. Turpin, “Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 2, pp. 732–737, 2001.
[89]
M. Erdogan, A. Canataroglu, S. Ganidagli, and M. Kulaks？zoglu, “Metabolic syndrome prevelance in subclinic and overt hypothyroid patients and the relation among metabolic syndrome parameters,” Journal of Endocrinological Investigation. In press.
[90]
G. Dimitriadis, P. Mitrou, V. Lambadiari et al., “Insulin action in adipose tissue and muscle in hypothyroidism,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 12, pp. 4930–4937, 2006.
[91]
O. Giménez-Palop, G. Giménez-Pérez, D. Mauricio et al., “Circulating ghrelin in thyroid dysfunction is related to insulin resistance and not to hunger, food intake or anthropometric changes,” European Journal of Endocrinology, vol. 153, no. 1, pp. 73–79, 2005.
[92]
A. Caixàs, R. Tirado, J. Vendrell et al., “Plasma visfatin concentrations increase in both hyper and hypothyroid subjects after normalization of thyroid function and are not related to insulin resistance, anthropometric or inflammatory parameters,” Clinical Endocrinology, vol. 71, no. 5, pp. 733–738, 2009.
[93]
G. Dimitriadis, E. Maratou, E. Boutati et al., “IGF-I increases the recruitment of GLUT4 and GLUT3 glucose transporters on cell surface in hyperthyroidism,” European Journal of Endocrinology, vol. 158, no. 3, pp. 361–366, 2008.
[94]
G. Dimitriadis, M. Parry-Billings, S. Bevan et al., “The effects of insulin on transport and metabolism of glucose in skeletal muscle from hyperthyroid and hypothyroid rats,” European Journal of Clinical Investigation, vol. 27, no. 6, pp. 475–483, 1997.
[95]
E. ？akal, A. T. Turgut, B. Demirbas et al., “Effects of L-thyroxine replacement therapy on carotid intima-media thickness in patients with primary hypothyroidism,” Experimental and Clinical Endocrinology and Diabetes, vol. 117, no. 6, pp. 294–300, 2009.
[96]
T. Nagasaki, M. Inaba, Y. Kumeda et al., “Decrease of arterial stiffness at common carotid artery in hypothyroid patients by normalization of thyroid function,” Biomedicine and Pharmacotherapy, vol. 59, no. 1-2, pp. 8–14, 2005.
[97]
L. Vanhaelst, P. Neve, and P. A. Bastenie, “Coronary-artery disease in myxoedema,” The Lancet, vol. 2, no. 7528, pp. 1257–1258, 1967.
[98]
A. D. Steinberg, “Myxedema and coronary artery disease–a comparative autopsy study,” Annals of Internal Medicine, vol. 68, no. 2, pp. 338–344, 1968.
[99]
A. I. Qureshi, M. F. K. Suri, A. Nasar, J. F. Kirmani, A. A. Divani, and W. H. Giles, “Free Thyroxine Index and risk of stroke: results from the National Health and Nutrition Examination Survey follow-up study,” Medical Science Monitor, vol. 12, no. 12, pp. CR501–CR506, 2006.
[100]
D. Liu, F. Jiang, Z. Shan et al., “A cross-sectional survey of relationship between serum TSH level and blood pressure,” Journal of Human Hypertension, vol. 24, no. 2, pp. 134–138, 2010.
[101]
T. Nagasaki, M. Inaba, Y. Kumeda et al., “Increased pulse wave velocity in subclinical hypothyroidism,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 1, pp. 154–158, 2006.
[102]
Y. Duan, W. Peng, X. Wang et al., “Community-based study of the association of subclinical thyroid dysfunction with blood pressure,” Endocrine, vol. 35, no. 2, pp. 136–142, 2009.
[103]
J. P. Walsh, A. P. Bremner, M. K. Bulsara et al., “Subclinical thyroid dysfunction and blood pressure: a community-based study,” Clinical Endocrinology, vol. 65, no. 4, pp. 486–491, 2006.
[104]
F. Toruner, A. E. Altinova, A. Karakoc et al., “Risk factors for cardiovascular disease in patients with subclinical hypothyroidism,” Advances in Therapy, vol. 25, no. 5, pp. 430–437, 2008.
[105]
E. ？engul, B. ？etinarslan, I. Tarkun, Z. Cantürk, and E. Türemen, “Homocysteine concentrations in subclinical hypothyroidism,” Endocrine Research, vol. 30, no. 3, pp. 351–359, 2004.
[106]
R. D. Lindeman, L. J. Romero, D. S. Schade, S. Wayne, R. N. Baumgartner, and P. J. Garry, “Impact of subclinical hypothyroidism on serum total homocysteine concentrations, the prevalence of coronary heart disease (CHD), and CHD risk factors in the New Mexico Elder Health Survey,” Thyroid, vol. 13, no. 6, pp. 595–600, 2003.
[107]
W. J. Hueston, D. E. King, and M. E. Geesey, “Serum biomarkers for cardiovascular inflammation in subclinical hypothyroidism,” Clinical Endocrinology, vol. 63, no. 5, pp. 582–587, 2005.
[108]
R. Luboshitzky, A. Aviv, P. Herer, and L. Lavie, “Risk factors for cardiovascular disease in women with subclinical hypothyroidism,” Thyroid, vol. 12, no. 5, pp. 421–425, 2002.
[109]
A. R. Cappola, L. P. Fried, A. M. Arnold et al., “Thyroid status, cardiovascular risk, and mortality in older adults,” Journal of the American Medical Association, vol. 295, no. 9, pp. 1033–1041, 2006.
[110]
C. H. Jung, K. C. Sung, H. S. Shin et al., “Thyroid dysfunction and their relation to cardiovascular risk factors such as lipid profile, hsCRP, and waist hip ratio in Korea,” The Korean Journal of Internal Medicine, vol. 18, no. 3, pp. 146–153, 2003.
[111]
A. Tuzcu, M. Bahceci, D. Gokalp, Y. Tuzun, and K. Gunes, “Subclinical hypothyroidism may be associated with elevated high-sensitive C-reactive protein (low grade inflammation) and fasting hyperinsulinemia,” Endocrine Journal, vol. 52, no. 1, pp. 89–94, 2005.
[112]
S. Razvi, J. U. Weaver, M. P. Vanderpump, and S. H. S. Pearce, “The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham survey cohort,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 4, pp. 1734–1740, 2010.
[113]
S. Singh, J. Duggal, J. Molnar, F. Maldonado, C. P. Barsano, and R. Arora, “Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis,” International Journal of Cardiology, vol. 125, no. 1, pp. 41–48, 2008.
[114]
N. Rodondi, D. Aujesky, E. Vittinghoff, J. Cornuz, and D. C. Bauer, “Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis,” American Journal of Medicine, vol. 119, no. 7, pp. 541–551, 2006.
[115]
N. Ochs, R. Auer, D. C. Bauer et al., “Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality,” Annals of Internal Medicine, vol. 148, no. 11, pp. 832–845, 2008.
[116]
S. Razvi, A. Shakoor, M. Vanderpump, J. U. Weaver, and S. H.S. Pearce, “The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 8, pp. 2998–3007, 2008.
[117]
B. K. Goksel, M. Karatas, A. Nebioglu et al., “Subclinical hypothyroidism, hyperhomocysteinemia and dyslipidemia: investigating links with ischemic stroke in Turkish patients,” Neurological Research, vol. 29, no. 8, pp. 871–876, 2007.
[118]
S. K. Jeong, J. Y. Seo, H. S. Nam, and H. K. Park, “Thyroid function and internal carotid artery stenosis in ischemic stroke,” Endocrine Journal, vol. 57, no. 8, pp. 711–718, 2010.
[119]
M. Alevizaki, M. Synetou, K. Xynos, C. C. Alevizaki, and K. N. Vemmos, “Hypothyroidism as a protective factor in acute stroke patients,” Clinical Endocrinology, vol. 65, no. 3, pp. 369–372, 2006.
[120]
J. H. Baek, P. W. Chung, Y. B. Kim et al., “Favorable influence of subclinical hypothyroidism on the functional outcomes in stroke patients,” Endocrine Journal, vol. 57, no. 1, pp. 23–29, 2010.
[121]
N. Rodondi, A. B. Newman, E. Vittinghoff et al., “Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death,” Archives of Internal Medicine, vol. 165, no. 21, pp. 2460–2466, 2005.
[122]
L. M. Prisant, J. S. Gujral, and A. L. Mulloy, “Hyperthyroidism: a secondary cause of isolated systolic hypertension,” Journal of Clinical Hypertension, vol. 8, no. 8, pp. 596–599, 2006.
[123]
K. M. Colleran, D. M. Ratliff, and M. R. Burge, “Potential association of thyrotoxicosis with vitamin B and folate deficiencies, resulting in risk for hyperhomocysteinemia and subsequent thromboembolic events,” Endocrine Practice, vol. 9, no. 4, pp. 290–295, 2003.
[124]
P. Mitrou, E. Boutati, V. Lambadiari et al., “Insulin resistance in hyperthyroidism: the role of IL6 and TNFα,” European Journal of Endocrinology, vol. 162, no. 1, pp. 121–126, 2010.
[125]
G. Dimitriadis, P. Mitrou, V. Lambadiari et al., “Glucose and lipid fluxes in the adipose tissue after meal ingestion in hyperthyroidism,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 3, pp. 1112–1118, 2006.
[126]
J. Al Jaber, S. Haque, H. Noor, B. Ibrahim, and J. Al Suwaidi, “Thyrotoxicosis and coronary artery spasm: case report and review of the literature,” Angiology, vol. 61, no. 8, pp. 807–812, 2010.
[127]
R. A. Chudleigh and J. S. Davies, “Graves' thyrotoxicosis and coronary artery spasm,” Postgraduate Medical Journal, vol. 83, no. 985, article e5, 2007.
[128]
Y. H. Choi, J. H. Chung, S. W. Bae et al., “Severe coronary artery spasm can be associated with hyperthyroidism,” Coronary Artery Disease, vol. 16, no. 3, pp. 135–139, 2005.
[129]
J. J. Sheu, J. H. Kang, H. C. Lin, and H. C. Lin, “Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study,” Stroke, vol. 41, no. 5, pp. 961–966, 2010.
[130]
J. S. Staffurth, M. C. Gibberd, and S. N. Fui, “Arterial embolism in thyrotoxicosis with atrial fibrillation,” British Medical Journal, vol. 2, no. 6088, pp. 688–690, 1977.
[131]
S. Bar-Sela, M. Ehrenfeld, and M. Eliakim, “Arterial embolism in thyrotoxicosis with atrial fibrillation,” Archives of Internal Medicine, vol. 141, no. 9, pp. 1191–1192, 1981.
[132]
A. Squizzato, V. E. A. Gerdes, D. P. M. Brandjes, H. R. Büller, and J. Stam, “Thyroid diseases and cerebrovascular disease,” Stroke, vol. 36, no. 10, pp. 2302–2310, 2005.
[133]
H. V？lzke, T. Ittermann, C. O. Schmidt et al., “Subclinical hyperthyroidism and blood pressure in a population-based prospective cohort study,” European Journal of Endocrinology, vol. 161, no. 4, pp. 615–621, 2009.
[134]
H. V？lzke, D. M. Robinson, U. Schminke et al., “Thyroid function and carotid wall thickness,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 5, pp. 2145–2149, 2004.
