Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease

Author(s): Mirjana Stojković and Miloš Žarković*

Volume 26, Issue 43, 2020

Page: [5617 - 5627] Pages: 11

DOI: 10.2174/1381612826666201118094747

Price: $65


The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD’s role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

Keywords: Subclinical hypothyroidism, subclinical hyperthyroidism, cardiovascular disease, coronary disease, heart failure, atrial fibrillation.

Reichlin S, Utiger RD. Regulation of the pituitary-thyroid axis in man: relationship of TSH concentration to concentration of free and total thyroxine in plasma. J Clin Endocrinol Metab 1967; 27(2): 251-5.
[] [PMID: 4163614]
Spencer CA, LoPresti JS, Patel A, et al. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab 1990; 70(2): 453-60.
[] [PMID: 2105333]
Benhadi N, Fliers E, Visser TJ, Reitsma JB, Wiersinga WM. Pilot study on the assessment of the setpoint of the hypothalamus-pituitary-thyroid axis in healthy volunteers. Eur J Endocrinol 2010; 162(2): 323-9.
[] [PMID: 19926783]
Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977; 7(6): 481-93.
[] [PMID: 598014]
Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87(2): 489-99.
[] [PMID: 11836274]
Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the Framingham Study. Arch Intern Med 1985; 145(8): 1386-8.
[] [PMID: 4026469]
Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291(2): 228-38.
[] [PMID: 14722150]
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160(4): 526-34.
[] [PMID: 10695693]
Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf) 1991; 34(1): 77-83.
[] [PMID: 2004476]
Bell RJ, Rivera-Woll L, Davison SL, Topliss DJ, Donath S, Davis SR. Well-being, health-related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease - a community-based study. Clin Endocrinol (Oxf) 2007; 66(4): 548-56.
[] [PMID: 17371474]
Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E, Knudsen PR. Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark. J Clin Endocrinol Metab 1998; 83(3): 765-9.
[] [PMID: 9506723]
Iervasi G, Molinaro S, Landi P, et al. Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch Intern Med 2007; 167(14): 1526-32.
[] [PMID: 17646607]
Walsh JP, Bremner AP, Bulsara MK, et al. Subclinical thyroid dysfunction and blood pressure: a community-based study. Clin Endocrinol (Oxf) 2006; 65(4): 486-91.
[] [PMID: 16984241]
Bagchi N, Brown TR, Parish RF. Thyroid dysfunction in adults over age 55 years. A study in an urban US community. Arch Intern Med 1990; 150(4): 785-7.
[] [PMID: 2109585]
Teng W, Shan Z, Teng X, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med 2006; 354(26): 2783-93.
[] [PMID: 16807415]
Boekholdt SM, Titan SM, Wiersinga WM, et al. Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk prospective population study. Clin Endocrinol (Oxf) 2010; 72(3): 404-10.
[] [PMID: 19486022]
Jabbar A, Pingitore A, Pearce SHS, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol 2017; 14(1): 39-55.
[] [PMID: 27811932]
Asvold BO, Vatten LJ, Nilsen TIL, Bjøro T. The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Eur J Endocrinol 2007; 156(2): 181-6.
[] [PMID: 17287407]
Rodondi N, Aujesky D, Vittinghoff E, Cornuz J, Bauer DC. Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Am J Med 2006; 119(7): 541-51.
[] [PMID: 16828622]
Ochs N, Auer R, Bauer DC, et al. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med 2008; 148(11): 832-45.
[] [PMID: 18490668]
Singh S, Duggal J, Molnar J, Maldonado F, Barsano CP, Arora R. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis. Int J Cardiol 2008; 125(1): 41-8.
[] [PMID: 17434631]
Rodondi N, den Elzen WP, Bauer DC, et al. Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010; 304(12): 1365-74.
[] [PMID: 20858880]
Sun J, Yao L, Fang Y, et al. Relationship between Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. Int J Endocrinol 2017; 2017: 8130796.
[] [PMID: 29081800]
de Miranda EJFP, Bittencourt MS, Staniak HL, et al. Thyrotropin and free thyroxine levels and coronary artery disease: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Braz J Med Biol Res 2018; 51(5): e7196.
[] [PMID: 29561960]
Park YJ, Lee YJ, Choi S-I, Chun E-J, Jang HC, Chang H-J. Impact of subclinical hypothyroidism on the coronary artery disease in apparently healthy subjects. Eur J Endocrinol 2011; 165(1): 115-21.
[] [PMID: 21490120]
Auer J, Berent R, Weber T, Lassnig E, Eber B. Thyroid function is associated with presence and severity of coronary atherosclerosis. Clin Cardiol 2003; 26(12): 569-73.
[] [PMID: 14677810]
Ortolani PD Jr, Romaldini JH, Guerra RA, Portes ES, Meireles GCX, Pimenta J. Association of serum thyrotropin levels with coronary artery disease documented by quantitative coronary angiography: a transversal study. Arch Endocrinol Metab 2018; 62(4): 410-5.
[] [PMID: 30304104]
Collet T-H, Gussekloo J, Bauer DC, et al. Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012; 172(10): 799-809.
[] [PMID: 22529182]
Gencer B, Collet T-H, Virgini V, et al. Thyroid Studies Collaboration. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation 2012; 126(9): 1040-9.
[] [PMID: 22821943]
Yang G, Wang Y, Ma A, Wang T. Subclinical thyroid dysfunction is associated with adverse prognosis in heart failure patients with reduced ejection fraction. BMC Cardiovasc Disord 2019; 19(1): 83.
[] [PMID: 30947691]
Nanchen D, Gussekloo J, Westendorp RGJ, et al. PROSPER Group. Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk. J Clin Endocrinol Metab 2012; 97(3): 852-61.
[] [PMID: 22238391]
Zoltek M, Andersson TM-L, Hedman C, Ihre-Lundgren C, Nordenvall C. Cardiovascular Incidence in 6900 Patients with Differentiated Thyroid Cancer: a Swedish Nationwide Study. World J Surg 2020; 44(2): 436-41.
[] [PMID: 31659412]
Chaker L, Heeringa J, Dehghan A, et al. Normal Thyroid Function and the Risk of Atrial Fibrillation: the Rotterdam Study. J Clin Endocrinol Metab 2015; 100(10): 3718-24.
[] [PMID: 26262438]
Chaker L, van den Berg ME, Niemeijer MN, et al. Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study. Circulation 2016; 134(10): 713-22.
[] [PMID: 27601558]
Baumgartner C, da Costa BR, Collet T-H, et al. Thyroid Studies Collaboration. Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. Circulation 2017; 136(22): 2100-16.
[] [PMID: 29061566]
Kannan L, Shaw PA, Morley MP, et al. Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes. Circ Heart Fail 2018; 11(12): e005266.
[] [PMID: 30562095]
Larsson SC, Allara E, Mason AM, Michaëlsson K, Burgess S. Thyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases. Circ Genom Precis Med 2019; 12(3): e002468.
[] [PMID: 30702347]
Touboul P-J, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis 2012; 34(4): 290-6.
[] [PMID: 23128470]
Stoner L, Sabatier MJ. Use of ultrasound for non-invasive assessment of flow-mediated dilation. J Atheroscler Thromb 2012; 19(5): 407-21.
[] [PMID: 22659525]
Gong N, Gao C, Chen X, Fang Y, Tian L. Endothelial Function in Patients with Subclinical Hypothyroidism: A Meta-Analysis. Horm Metab Res 2019; 51(11): 691-702.
[] [PMID: 31683338]
Zhao T, Chen B, Zhou Y, et al. Effect of levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: a meta-analysis. BMJ Open 2017; 7(10): e016053.
[] [PMID: 29061604]
Masaki M, Komamura K, Goda A, et al. Elevated arterial stiffness and diastolic dysfunction in subclinical hypothyroidism. Circ J 2014; 78(6): 1494-500.
[] [PMID: 24694766]
Kim H, Kim TH, Kim HI, et al. Subclinical thyroid dysfunction and risk of carotid atherosclerosis. PLoS One 2017; 12(7): e0182090.
[] [PMID: 28750042]
Delitala AP, Filigheddu F, Orrù M, et al. No evidence of association between subclinical thyroid disorders and common carotid intima medial thickness or atherosclerotic plaque. Nutr Metab Cardiovasc Dis 2015; 25(12): 1104-10.
[] [PMID: 26615224]
Yildiz C, Altay M, Yildiz S, et al. Arterial stiffness in hyperthyroid patients is deteriorated due to thyroid hormones. Arch Endocrinol Metab 2019; 63(3): 258-64.
[] [PMID: 31066760]
Wang J, Zheng X, Sun M, et al. REACTION Study Group. Low serum free thyroxine concentrations associate with increased arterial stiffness in euthyroid subjects: a population-based cross-sectional study. Endocrine 2015; 50(2): 465-73.
[] [PMID: 25987347]
Squizzato A, Gerdes VEA, Brandjes DPM, Büller HR, Stam J. Thyroid diseases and cerebrovascular disease. Stroke 2005; 36(10): 2302-10.
[] [PMID: 16179578]
Chaker L, Baumgartner C, Ikram MA, et al. Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis. Eur J Epidemiol 2014; 29(11): 791-800.
[] [PMID: 25179793]
Zhang X, Xie Y, Ding C, et al. Subclinical hypothyroidism and risk of cerebral small vessel disease: A hospital-based observational study. Clin Endocrinol (Oxf) 2017; 87(5): 581-6.
[] [PMID: 28543314]
Dhital R, Poudel DR, Tachamo N, et al. Ischemic Stroke and Impact of Thyroid Profile at Presentation: A Systematic Review and Meta-analysis of Observational Studies. J Stroke Cerebrovasc Dis 2017; 26(12): 2926-34.
[] [PMID: 28821377]
Yang LB, Jiang DQ, Qi WB, et al. Subclinical hyperthyroidism and the risk of cardiovascular events and all-cause mortality: an updated meta-analysis of cohort studies. Eur J Endocrinol 2012; 167(1): 75-84.
[] [PMID: 22535645]
Zhu L, Gao C, Wang X, et al. The effect of low FT3 levels on coronary artery calcification and MACE in outpatients with suspected coronary artery disease. Coron Artery Dis 2014; 25(5): 427-32.
[] [PMID: 24525790]
Moon S, Kim MJ, Yu JM, Yoo HJ, Park YJ. Subclinical hypothyroidism and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Thyroid 2018; 28(9): 1101-10.
[] [PMID: 29978767]
Selmer C, Olesen JB, Hansen ML, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab 2014; 99(7): 2372-82.
[] [PMID: 24654753]
Inoue K, Tsujimoto T, Saito J, Sugiyama T. Association Between Serum Thyrotropin Levels and Mortality Among Euthyroid Adults in the United States. Thyroid 2016; 26(10): 1457-65.
[] [PMID: 27539006]
Inoue K, Ritz B, Brent GA, Ebrahimi R, Rhee CM, Leung AM. Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality. JAMA Netw Open 2020; 3(2): e1920745.
[] [PMID: 32031647]
van de Ven AC, Netea-Maier RT, de Vegt F, et al. Associations between thyroid function and mortality: the influence of age. Eur J Endocrinol 2014; 171(2): 183-91.
[] [PMID: 24801590]
Gussekloo J, van Exel E, de Craen AJM, Meinders AE, Frölich M, Westendorp RGJ. Thyroid status, disability and cognitive function, and survival in old age. JAMA 2004; 292(21): 2591-9.
[] [PMID: 15572717]
Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 2009; 94(4): 1251-4.
[] [PMID: 19158193]
Cai Y, Ren Y, Shi J. Blood pressure levels in patients with subclinical thyroid dysfunction: a meta-analysis of cross-sectional data. Hypertens Res 2011; 34(10): 1098-105.
[] [PMID: 21796125]
Zhang J, Huang C, Meng Z, et al. Gender-Specific Differences on the Association of Hypertension with Subclinical Thyroid Dysfunction. Int J Endocrinol 2019; 2019: 6053068.
[] [PMID: 32082373]
Polat Canbolat I, Belen E, Bayyigit A, Helvaci A, Kilickesmez K. Evaluation of Daily Blood Pressure Alteration in Subclinical Hypothyroidism. Acta Cardiol Sin 2017; 33(5): 489-94.
[PMID: 28959101]
Iqbal A, Figenschau Y, Jorde R. Blood pressure in relation to serum thyrotropin: The Tromsø study. J Hum Hypertens 2006; 20(12): 932-6.
[] [PMID: 17024137]
Chang Y-C, Hua S-C, Chang C-H, et al. High TSH Level within Normal Range Is Associated with Obesity, Dyslipidemia, Hypertension, Inflammation, Hypercoagulability, and the Metabolic Syndrome: A Novel Cardiometabolic Marker. J Clin Med 2019; 8(6): E817.
[] [PMID: 31181658]
Ittermann T, Thamm M, Wallaschofski H, Rettig R, Völzke H. Serum thyroid-stimulating hormone levels are associated with blood pressure in children and adolescents. J Clin Endocrinol Metab 2012; 97(3): 828-34.
[] [PMID: 22205713]
Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol 2012; 119(2 Pt 1): 315-20.
[] [PMID: 22270283]
He W, Li S, Zhang J-A, Zhang J, Mu K, Li X-M. Effect of Levothyroxine on Blood Pressure in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2018; 9: 454.
[] [PMID: 30154757]
Mason RL, Hunt HM, Hurxthal Lewis M. Blood cholesterol values in hyperthyroidism and hypothyroidism: their significance. N Engl J Med 1930; 203: 1273-8.
Liu X-L, He S, Zhang S-F, et al. Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis. Med Sci Monit 2014; 20: 1432-41.
[] [PMID: 25124461]
Pearce EN. Update in lipid alterations in subclinical hypothyroidism. J Clin Endocrinol Metab 2012; 97(2): 326-33.
[] [PMID: 22205712]
Delitala AP, Fanciulli G, Maioli M, Delitala G. Subclinical hypothyroidism, lipid metabolism and cardiovascular disease. Eur J Intern Med 2017; 38: 17-24.
[] [PMID: 28040402]
Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002; 87(4): 1533-8.
[] [PMID: 11932277]
Milionis HJ, Efstathiadou Z, Tselepis AD, et al. Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine. Thyroid 2003; 13(4): 365-9.
[] [PMID: 12804105]
Anagnostis P, Efstathiadou ZA, Slavakis A, et al. The effect of L-thyroxine substitution on lipid profile, glucose homeostasis, inflammation and coagulation in patients with subclinical hypothyroidism. Int J Clin Pract 2014; 68(7): 857-63.
[] [PMID: 24548294]
Duntas LH, Mantzou E, Koutras DA. Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism. Thyroid 2002; 12(11): 1003-7.
[] [PMID: 12490078]
Pearce EN, Wilson PWF, Yang Q, Vasan RS, Braverman LE. Thyroid function and lipid subparticle sizes in patients with short-term hypothyroidism and a population-based cohort. J Clin Endocrinol Metab 2008; 93(3): 888-94.
[] [PMID: 18073305]
Kim CS, Kang JG, Lee SJ, et al. Relationship of low-density lipoprotein (LDL) particle size to thyroid function status in Koreans. Clin Endocrinol (Oxf) 2009; 71(1): 130-6.
[] [PMID: 19178521]
Sigal GA, Tavoni TM, Silva BMO, et al. Subclinical Hyperthyroidism: Status of the Cholesterol Transfers to HDL and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer. Front Endocrinol (Lausanne) 2020; 11: 176.
[] [PMID: 32300332]
Türemen EE, Çetinarslan B, Şahin T, Cantürk Z, Tarkun İ. Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis. Endocr J 2011; 58(5): 349-54.
[] [PMID: 21490407]
Gupta G, Sharma P, Kumar P, Itagappa M. Study on subclinical hypothyroidism and its association with various inflammatory markers. J Clin Diagn Res 2015; 9(11): BC04-6.
[] [PMID: 26674140]
Taddei S, Caraccio N, Virdis A, et al. Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto’s thyroiditis. J Clin Endocrinol Metab 2006; 91(12): 5076-82.
[] [PMID: 16968790]
Dardano A, Ghiadoni L, Plantinga Y, et al. Recombinant human thyrotropin reduces endothelium-dependent vasodilation in patients monitored for differentiated thyroid carcinoma. J Clin Endocrinol Metab 2006; 91(10): 4175-8.
[] [PMID: 16868055]
Milani AT, Khadem-Ansari MH, Rasmi Y. Effects of thyroxine on adhesion molecules and proinflammatory cytokines secretion on human umbilical vein endothelial cells. Res Pharm Sci 2019; 14(3): 237-46.
[] [PMID: 31160901]
Popławska-Kita A, Siewko K, Telejko B, et al. The changes in the endothelial function and haemostatic and inflammatory parameters in subclinical and overt hyperthyroidism. Int J Endocrinol 2013; 2013: 981638.
[] [PMID: 24367378]
Gazdag A, Nagy EV, Burman KD, Paragh G, Jenei Z. Improved endothelial function and lipid profile compensate for impaired hemostatic and inflammatory status in iatrogenic chronic subclinical hyperthyroidism of thyroid cancer patients on L-t4 therapy. Exp Clin Endocrinol Diabetes 2010; 118(6): 381-7.
[] [PMID: 19658059]
Manfredi E, van Zaane B, Gerdes VEA, Brandjes DPM, Squizzato A. Hypothyroidism and acquired von Willebrand’s syndrome: a systematic review. Haemophilia 2008; 14(3): 423-33.
[] [PMID: 18218015]
Elbers LPB, Fliers E, Cannegieter SC. The influence of thyroid function on the coagulation system and its clinical consequences. J Thromb Haemost 2018; 16(4): 634-45.
[] [PMID: 29573126]
Ordookhani A, Burman KD. Hemostasis in Overt and Subclinical Hyperthyroidism. Int J Endocrinol Metab 2017; 15(3): e44157.
[PMID: 29201071]
Ordookhani A, Burman KD. Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders. Int J Endocrinol Metab 2017; 15(2): e42649.
[] [PMID: 29026409]
Fernández-Real J-M, López-Bermejo A, Castro A, Casamitjana R, Ricart W. Thyroid function is intrinsically linked to insulin sensitivity and endothelium-dependent vasodilation in healthy euthyroid subjects. J Clin Endocrinol Metab 2006; 91(9): 3337-43.
[] [PMID: 16804039]
Vyakaranam S, Vanaparthy S, Nori S, Palarapu S, Bhongir AV. Study of Insulin Resistance in Subclinical Hypothyroidism. Int J Health Sci Res 2014; 4(9): 147-53.
[PMID: 25580384]
Peeters RP, van der Deure WM, van den Beld AW, et al. The Asp727Glu polymorphism in the TSH receptor is associated with insulin resistance in healthy elderly men. Clin Endocrinol (Oxf) 2007; 66(6): 808-15.
[] [PMID: 17408423]
Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006; 113(15): 1888-904.
[] [PMID: 16618833]
Potenza MA, Marasciulo FL, Chieppa DM, et al. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol 2005; 289(2): H813-22.
[] [PMID: 15792994]
Rezzonico J, Niepomniszcze H, Rezzonico M, Pusiol E, Alberto M, Brenta G. The association of insulin resistance with subclinical thyrotoxicosis. Thyroid 2011; 21(9): 945-9.
[] [PMID: 21834678]
Porcellini A, Messina S, De Gregorio G, et al. The expression of the thyroid-stimulating hormone (TSH) receptor and the cAMP-dependent protein kinase RII beta regulatory subunit confers TSH-cAMP-dependent growth to mouse fibroblasts. J Biol Chem 2003; 278(42): 40621-30.
[] [PMID: 12902333]
Agretti P, Chiovato L, De Marco G, et al. Real-time PCR provides evidence for thyrotropin receptor mRNA expression in orbital as well as in extraorbital tissues. Eur J Endocrinol 2002; 147(6): 733-9.
[] [PMID: 12457447]
Balzan S, Del Carratore R, Nicolini G, et al. TSH induces co-localization of TSH receptor and Na/K-ATPase in human erythrocytes. Cell Biochem Funct 2009; 27(5): 259-63.
[] [PMID: 19466745]
Bell A, Gagnon A, Grunder L, Parikh SJ, Smith TJ, Sorisky A. Functional TSH receptor in human abdominal preadipocytes and orbital fibroblasts. Am J Physiol Cell Physiol 2000; 279(2): C335-40.
[] [PMID: 10912999]
Balzan S, Del Carratore R, Nicolini G, et al. Proangiogenic effect of TSH in human microvascular endothelial cells through its membrane receptor. J Clin Endocrinol Metab 2012; 97(5): 1763-70.
[] [PMID: 22419707]
Drvota V, Janson A, Norman C, et al. Evidence for the presence of functional thyrotropin receptor in cardiac muscle. Biochem Biophys Res Commun 1995; 211(2): 426-31.
[] [PMID: 7794253]
Zhang W, Tian LM, Han Y, et al. Presence of thyrotropin receptor in hepatocytes: not a case of illegitimate transcription. J Cell Mol Med 2009; 13(11-12): 4636-42.
[] [PMID: 19187127]
Bell A, Gagnon A, Sorisky A. TSH stimulates IL-6 secretion from adipocytes in culture. Arterioscler Thromb Vasc Biol 2003; 23(12): e65-6.
[] [PMID: 14672881]
Fernandez-Ruocco J, Gallego M, Rodriguez-de-Yurre A, et al. High Thyrotropin Is Critical for Cardiac Electrical Remodeling and Arrhythmia Vulnerability in Hypothyroidism. Thyroid 2019; 29(7): 934-45.
[] [PMID: 31084419]
Monzani F, Di Bello V, Caraccio N, et al. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab 2001; 86(3): 1110-5.
[] [PMID: 11238494]
Ripoli A, Pingitore A, Favilli B, et al. Does subclinical hypothyroidism affect cardiac pump performance? Evidence from a magnetic resonance imaging study. J Am Coll Cardiol 2005; 45(3): 439-45.
[] [PMID: 15680725]
Villar HCCE, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev 2007; (3): CD003419.
[PMID: 17636722]
Razvi S, Weaver JU, Butler TJ, Pearce SHS. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med 2012; 172(10): 811-7.
[] [PMID: 22529180]
Mooijaart SP, Du Puy RS, Stott DJ, et al. Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism. JAMA 2019; 322(20): 1-11.
[] [PMID: 31664429]
de Montmollin M, Feller M, Beglinger S, et al. L-Thyroxine Therapy for Older Adults With Subclinical Hypothyroidism and Hypothyroid Symptoms: Secondary Analysis of a Randomized Trial. Ann Intern Med 2020; 172(11): 709-16.
[] [PMID: 32365355]
Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 2010; 95(1): 186-93.
[] [PMID: 19906785]
Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2015; 162(1): 35-45.
[] [PMID: 25347444]
Garber JR, Cobin RH, Gharib H, et al. American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012; 18(6): 988-1028.
[] [PMID: 23246686]
Pearce SHS, Brabant G, Duntas LH, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J 2013; 2(4): 215-28.
[] [PMID: 24783053]
Hadlow NC, Rothacker KM, Wardrop R, Brown SJ, Lim EM, Walsh JP. The relationship between TSH and free T₄ in a large population is complex and nonlinear and differs by age and sex. J Clin Endocrinol Metab 2013; 98(7): 2936-43.
[] [PMID: 23671314]
Boucai L, Hollowell JG, Surks MI. An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. Thyroid 2011; 21(1): 5-11.
[] [PMID: 21058882]
Milinković N, Ignjatović S, Žarković M, et al. Indirect estimation of age-related reference limits of thyroid parameters: a cross-sectional study of outpatients’ results. Scand J Clin Lab Invest 2014; 74(5): 378-84.
[] [PMID: 24684474]
Biondi B, Fazio S, Carella C, et al. Control of adrenergic overactivity by beta-blockade improves the quality of life in patients receiving long term suppressive therapy with levothyroxine. J Clin Endocrinol Metab 1994; 78(5): 1028-33.
[PMID: 8175955]
Sgarbi JA, Villaça FG, Garbeline B, Villar HE, Romaldini JH. The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J Clin Endocrinol Metab 2003; 88(4): 1672-7.
[] [PMID: 12679455]
Kaminski G, Dziuk M, Szczepanek-Parulska E, Zybek-Kocik A, Ruchala M. Electrocardiographic and scintigraphic evaluation of patients with subclinical hyperthyroidism during workout. Endocrine 2016; 53(2): 512-9.
[] [PMID: 26860516]
Biondi B, Bartalena L, Cooper DS, Hegedüs L, Laurberg P, Kahaly GJ. The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism. Eur Thyroid J 2015; 4(3): 149-63.
[] [PMID: 26558232]
Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26(10): 1343-421.
[] [PMID: 27521067]
Azizi F, Malboosbaf R. Safety of long-term antithyroid drug treatment? A systematic review. J Endocrinol Invest 2019; 42(11): 1273-83.
[] [PMID: 31134536]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy