Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

An Overview of Influence of Thyroid Hormones on Cardiovascular Function


Affiliations
1 Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras-Taramani Campus, Chennai − 600113, Tamil Nadu., India
     

   Subscribe/Renew Journal


It has been very clearly established that thyroid hormones have a specific influence on cardio-vascular system. Hyper- or hypothyroidism induces cardiovascular disorders, atrial and ventricular arrhythmias, atherosclerotic vascular diseases, dyslipidemia and heart failure. Heart failure results from the impairment of ability of the ventricle to fill with or eject blood. Thyroid hormones contribute to cardiovascular events by directly acting on the cardiomyocyte via genomic and nongenomic pathways. Thyroid hormones play a critical role in maintaining cardiac homeostasis. Fluctuations in thyroid hormones due to hyper- or hypothyroidism has an adverse effect on the heart. Thyroid hormones have a direct influence on myocardial contractility, systolic and diastolic blood pressure, heart rate, heart mass, ejection fraction and heart output. Hyperthyroidism stimulates high cardiac output with low systemic vascular resistance and is associated with faster heart rate and increased left ventricular systolic and diastolic function and supraventricular atrial fibrillation. Hypothyroidism has an opposite effect on the heart rate and myocardial contractility. Hypothyroidism reduces cardiac repolarizing of K<sup>+</sup> currents such as transient outward potassium current and increase in L-type calcium current. Alterations in Thyroid Stimulating Hormone level bring about cardiac electrical disturbances. Subclinical hypothyroidism is associated with increased heart rate, atrial arrhythmias, LV mass and impaired ventricular relaxation, and increased risk of mortality due to cardio-vascular impairment. In this overview, with the available information and publications, the physiological and patho-physiological relationships between thyroid hormones and the cardiovascular system are discussed.

Keywords

Cardiovascular System, Hyperthyroidism, Hypothyroidism, Smooth Muscle Cells of the Vascular System, Subclinical Hypothyroidism, Thyroid Hormones, Thyroid Hormone Receptors, Thyroid Stimulating Hormone, Ventricular Contractions
Subscription Login to verify subscription
User
Notifications
Font Size


  • Fliers E, Alkemade A, Weirsinga WM, Swaab DF. Hypothalamic thyroid hormone feedback in health and disease. Progress in Brain Research. 2006; 153:189-207. https://doi.org/10.1016/S0079-6123(06)53011-0.
  • Klein I, Danzi S. Thyroid disease and the heart. Current Problems in Cardiology. 2107; 116(15):65-92. https://doi. org/10.1016/j.cpcardiol.2015.04.002. PMid:26792255.
  • Denttice M, Marsilli A, Zavacki A, et al. The deiodinase and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochimica et Biophysica Acta. 2013; 1830(7):3937-3945. https:// doi.org/10.1016/j.bbagen.2012.05.007, PMid:22634734 PMCid:PMC3670672.
  • Berger HR, Creech MK, Hannoush Z, et al. A novel mutation causing complete thyroid binding globulin deficiency in a male with coexisting Graves disease. AACE Clinical Case Reports. 2017; 3(2):e134-e139. https://doi.org/10.4158/ EP161421.CR, PMid:28553659 PMCid:PMC5444812.
  • Lin JZ, Sieglaff DH, Yuan C, et al. Gene specific actions of thyroid hormone receptor subtypes. PLoS One. 2013; 8(1):e52407 https://doi.org/10.1371/journal.pone.0052407. PMid:23300972 PMCid:PMC3536777.
  • Wiersing WM. The role of thyroid hormone nuclear receptors in the heart: evidence from pharmacological approaches. Heart Failure Reviews. 2010. 15(2):121- 124 https://doi.org/10.1007/s10741-008-9131-9. PMid: 19096930 PMCid:PMC2820686.
  • Klein I. Thyroid hormone and the cardiovascular system. New England Journal of Medicine. 1990; 88(6):631-637. https://doi.org/10.1016/0002-9343(90)90531-H.
  • Dillmann WH. Biochemical basis of thyroid hormone action in the heart. American Journal of Medicine. 1990; 88(6):626-630. https://doi.org/10.1016/0002- 9343(90)90530-Q.
  • Everts ME, Verhoeven FA, Bezstarosti K, et al. Uptake of thyroid hormone in neonatal rat cardiac myocytes. Endocrinology. 1996; 137(10):4235-4242 https://doi. org/10.1210/endo.137.10.8828482. PMid:8828482.
  • Brent GA. The molecular basis of thyroid hormone action. New England Journal of Medicine. 1994; 331(13):847- 853. https://doi.org/10.1056/NEJM199409293311306. PMid:8078532.
  • Kiss E, Jacab G, Kranias EG, Edes I. Thyroid hormoneinduced alteration in phospholamban protein expression regulatory effects on sarcoplasmic reticulum Ca2+ transport and myocardial relaxation. Circulation Research. 1994; 75(2):245-251. https://doi.org/10.1161/01.RES.75.2.245. PMid:8033338.
  • Morkin E. Regulation of myosin heavy chain genes in the heart. Circulation. 1993; 87(5):1451-1460. https://doi. org/10.1161/01.CIR.87.5.1451. PMid:8490999.
  • Ojamaa K, Klemperer JB, McGillivray SS, Samarel A. Thyroid hormone and hemodynamic regulation of betamyosin heavy chain promoter in the heart. Endocrinology. 1996; 137(3):802-808. https://doi.org/10.1210/ endo.137.3.8603588. PMid:8603588.
  • Ladenson PW. Thyrotoxicosis and heart something old and something new. Journal of Clinical Endocrinology and Metabolism. 1993; 7(2):332-333. https://doi.org/10.1210/ jcem.77.2.8345036. PMid: 8345036.
  • Varagas-Uricoechea H, Sierra-Torres CH. Thyroid hormones and the heart. Hormone Molecular Biology and Clinical Investigation. 2014; 18(1):15-26. https://doi. org/10.1515/hmbci-2013-0059. PMid:25438971.
  • Glick GG, Melikian J, Ismail-Beigi F. Thyroidal enhancement of rat myocardial Na.K-ATPase preferential expression of alpha-2 activity and mRNA abundance. Journal of Membrane Biology. 1990; 115(3):273-282. https://doi. org/10.1007/BF01868642. PMid:2165172.
  • Ojamaa K, Saber A, Kenessey A, Shenoy R, Klein I. Regulation of rat cardiac KvL.5 gene expression by thyroid hormone is rapid and chamber specific. Endocrinology. 1999; 140(7):3170-3176. https://doi.org/10.1210/ endo.140.7.6776. PMid:10385411.
  • Razvi S, Jabbar A, Pingitore A, et al. Thyroid hormones and cardiovascular function and diseases. Journal of American College of Cardiology. 2018; 71(16):1781-1796. https://doi. org/10.1016/j.jacc.2018.02.045. PMid:29673469.
  • Gerdes AM, Iervasi GG. Thyroid replacement therapy and heart failure. Circulation. 2010; 122(4):385-393. https:// doi.org/10.1161/CIRCULATIONAHA.109.917922. PMid: 20660814.
  • Villeneuve C, Guilbeau-Frugier CC, Sicard P, et al. p-53- PGC-1-alpha pathway mediates oxidative mitochondrial damage and cardiomyocyte necrosis induced monoamine oxidase-A upregulation: Role in chronic left ventricular dysfunction in mice. Antioxidants and Redox Signaling. 2013; 18(1):5-18. https://doi.org/10.1089/ars.2011.4373. PMid:22738191 PMCid:PMC3503466.
  • Davis PJ, Davis FB. Acute cellular actions of thyroid hormone and myocardial function. Annals of Thoracic Surgery. 1993; 56(1)(Suppl):S16-S23. https://doi. org/10.1016/0003-4975(93)90550-2.
  • Walkar JD, Crawford FA, Katu S. The novel effects of 3.5.3.triiodo- L thyronine on myocytes contractile function and beta adrenergic responsiveness in dilated cardiomyopathy. Journal of Thoracic Cardiovascular Surgery. 1994; 108(4):672-679. https://doi.org/10.1016/ S0022-5223(94)70292-6.
  • Ojamaa K, Kenessey A, Klein I. Thyroid hormone regulation of phospholamban phosphrylation in the rat heart. Endocrinology. 2002; 141(6):2139-2144. https://doi. org/10.1210/endo.141.6.7514. PMid:10830301.
  • Hoit, BD, Khoury, SF, Shao Y, et al. Effects of thyroid hormone on cardiac beta adrenergic responsiveness in conscious baboons. Circulation. 1997; 96(2):592-598. https://doi.org/10.1161/01.CIR.96.2.592. PMid:9244231.
  • Ojamaa K, Klein I, Saber A, Steinberg SF. Changes in adenylyl cyclase isoforms as a mechanism for thyroid hormone modulation of cardiac beta adrenergic receptor responsiveness. Metabolism. 2000; 49(2):275-279. https:// doi.org/10.1016/S0026-0495(00)92262-5.
  • Klemperer JD, Klein I, Gamez M, et al. Thyroid hormone treatment after coronary artery bypass surgery. New England Journal of Medicine. 1995; 333(23): 1522-1527. https://doi.org/10.1056/NEJM199512073332302. PMid:7477166.
  • Ojamaa K, Klemperer JD, Klein I. Acute effects of thyroid hormone on vascular smooth muscle. Thyroid. 1996; 6(5): 505-512. https://doi.org/10.1089/thy.1996.6.505. PMid:8936680.
  • Park KW, Dai HB, Ojamaa K, et al. The direct vasomotor effect of thyroid hormone on rat skeletal muscle arteries. Anesthesis and Analgesis. 1997; 85(4):734-738. https://doi. org/10.1213/00000539-199710000-00005.
  • McAllister RM, Delp MD, Laughlin MH. Thyroid status and exercise tolerance. Cardiovascular and metabolic consideration. Sports Medicine. 1995; 20(3):189-198. https://doi.org/10.2165/00007256-199520030-00005. PMid:8571001.
  • Klein I, Ojamaa K. Cardiovascular System in Hypothyroidism. In: Braverman IF, Utiger, RD. Eds. Werner and Ingbar’s The Thyroid: A Fundamental & Clinical Text. Edition 10. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 777-782.
  • Fredlund BO, Olsson SB. Long QT interval and ventricular tachycardia of “torsade de pointe” type in hypothyroidism. Acta medica Scandinavica. 1983; 213(3):1303-1308. https://doi.org/10.1111/j.0954-6820.1983.tb03724.x. PMid:6133415.
  • Dernellis J, Panaretou M. Effect of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism. American Heart Journal. 2002; 143(4):718-724. https://doi.org/10.1067/ mhj.2002.120766. PMid:11923811.
  • Obuobie K, Smith J, Evans LM, et al. Increased central arterial stiffness in hypothyroidism. Journal of Clinical Endocrinology & Metabolism. 2002; 87(10):4662-4666. https://doi.org/10.1210/jc.2002-020493. PMid:12364455.
  • Crowley WF Jr, Ridgway FC, Bough EW. Noninvasive evaluation of cardiac function in hyperthyroidism. Response to gradual thyroxine replacement. New England Journal of Medicine. 1977; 296(1):1-6. https://doi. org/10.1056/NEJM197701062960101. PMid:830262.
  • Wieshammer S, Keek FS, Waitzinger J, et al. Acute hypothyroidism shows the rate of left ventricular diastolic relaxation. Canadian Journal of Physiology and Pharmacology. 1989; 67(9):1007-1010. https://doi. org/10.1139/y89-158. PMid:2598125.
  • Keating FR, Parkin TW, Selby JB, Dickinson LS. Treatment of heart disease associated with myxedema. Progress in Cardiovascular Disease. 1960; 3(4):364-381. https://doi. org/10.1016/S0033-0620(61)90004-4.
  • Bengel FN, Nekolla SG, Ibrahim T, et al. Effects of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. Journal of Clinical Endocrinology and Metabolism. 2000; 85(5):1822-1827. https://doi.org/10.1210/jcem.85.5.6520. PMid:10843159.
  • McDermott MM, Feinglass J Sy, Gheorghiade M. Hospitalized congestive heart failure patients with preserved versus abnormal left ventricular systolic function clinical characteristics and drug therapy. American Journal of Medicine. 1995; 99(6):629-635. https://doi.org/10.1016/ S0002-9343(99)80250-2.
  • Di Bello V, Monzani F, Giorgi D, et al. Ultrasonic myocardial textural analysis in subclinical hypothyroidism. Journal of American Society of Echocardiography. 2002; 13(9):832-840. https://doi.org/10.1067/mje.2000.106397. PMid:10980086.
  • Vitale G, Galderisi M, Lupoli GA, et al. Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool pulsed tissue Doppler. Journal of Clinical Endocrinology and Metabolism. 2002; 87(9):4350-4355. https://doi.org/10.1210/jc.2002-011764. PMid:12213897.
  • Pingitore A, Landi P, Taddei, MC, et al. Triiodothyronine levels for risk stratification of patients with chronic heart failure. American Journal of Medicine. 2005; 118(2):132- 136. https://doi.org/10.1016/j.amjmed.2004.07.052. PMid:15694896.
  • Hak AE, Pols HA, Visser TJ, et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam study. Annals of Internal Medicine. 2000; 132(4):270-278. https://doi.org/10.7326/0003-4819- 132-4-200002150-00004. PMid:10681281.
  • Duntas LH. Thyroid disease and lipids. Thyroid. 2002; 12(4):287-293. https://doi. org/10.1089/10507250252949405.
  • Duntas LH, Mantou F, Koutras DA. Circulating levels of oxidized low density lipoprotein in overt and mild hypothyroidism. Thyroid. 2002; 12(11):1003-1007. https:// doi.org/10.1089/105072502320908349. PMid:12490078.
  • Lekakis J, Papamicheal C, Alivizaki N. Flow-mediated endothelium-dependent vasodilation is impaired in subjects with hypothyroidism, borderline hypothyroidism and high normal serum Thyrotropin (TSH) value. Thyroid. 1997; 7(3):411-414. https://doi.org/10.1089/thy.1997.7.411. PMid:9226212.
  • Muller B, Tsakiris DA, Roth CB, et al. Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. European Journal of Clinical Investigation. 1999; 31:131-137. https://doi.org/10.1046/ j.1365-2362.2001.00777.x. PMid:11168451.
  • Suh S, Kim DK. Subclinical hypothyroidism and cardiovascular disease. Endocrinology and Metabolism (Seoul). 2015; 30(3):246-251. https://doi.org/10.3803/ EnM.2015.30.3.246. PMid:26248862 PMCid:PMC4595347.
  • Warner MH, Beckett, GJ. Mechanisms behind the nonthyroidal illness syndrome: An update. Journal of Endocrinology. 2010; 205(1):1-13. https://doi.org/10.1677/ JOE-09-0412. PMid:641427.
  • Kaptein EM, Feinstein EI, Nicoloff JT, Massry SG. Serum reverse triiodithyronine and thyroxine kinetics in patients with chronic renal failure. Journal of Clinical Endocrinology and Metabolism. 1983; 57(1):181-189. https://doi.org/10.1210/jcem-57-1-181. PMid:6853675.
  • Peeters RP, Wouters PJ, Kaptein E, et al. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. Journal of Clinical Endocrinology and Metabolism. 2003; 88(7):3202-3211. https://doi. org/10.1210/jc.2002-022013. PMid:12843166.
  • Dentice M, Salvatore D. Deiodinases: The balance of thyroid hormone: Local impact of thyroid hormone inactivation. Journal of Endocrinology. 2011; 209(3):273-282. https:// doi.org/10.1530/JOE-11-0002. PMid:21398344.
  • Kimura T, Kanda T, Kotajima N, et al. Involvement of circulating interleukin-6 and its receptor in the development of euthyroid sick syndrome in patients with acute myocardial infarction. European Journal of Endocrinology. 2000; 143(2):179-184. https://doi. org/10.1530/eje.0.1430179. PMid:10913935.
  • Boelen A, Maas MA, Lowik CW, et al. Induced illness in interleukin-6 (IL-6) knockout mice: a casual role of IL-6 in the development of the low 3.5.3-triiodithyronime syndrome. Endocrinology. 1996; 137:5250-5254. https:// doi.org/10.1210/endo.137.12.8940342 PMid:8940342.
  • Zhang B, Peng W, Wang C, et al. A low fT3 level as a prognostic marker in patients with acute myocardial infarctions. Internal Medicine. 2012; 51(21):3009-3015. https://doi.org/10.2169/internalmedicine.51.7902. PMid:23124142.
  • Novitzky D, Cooper DK. Thyroid hormone and the stunned myocardium. Journal of Endocrinology. 2014; 223(1):R-1- 8. https://doi.org/10.1530/JOE-14-0389. PMid:25128568.
  • Nordyke RA, Gilbert FI Jr, Harada AS. Graves’ disease. Influence of age on clinical findings. Archives of Internal Medicine. 1988; 148(3):626-631. https://doi.org/10.1001/ archinte.1988.00380030132023, PMid:3341864.
  • Von Olshausen K, Bischoff S, Kahaly G, et al. Cardiac arrhythmias and heart rate in hyperthyroidism. American Journal of Cardiology. 1989; 63(13):930-933. https://doi. org/10.1016/0002-9149(89)90142-2.
  • Cacciatori V, Bellavere F, Pezzarossa A, et al. Power spectral analysis of heart rate in hypothyroidism. Journal of Clinical Endocrinology and Metabolism. 1996; 81(8):2828-2835. https://doi.org/10.1210/jcem.81.8.8768838. PMid:8768838.
  • Sun ZQ, Ojamaa Nakamura TY, et al. Thyroid hormone increases pace maker activity in rat arterial neonatal myocytes. Journal of Molecular and Cellular Cardiology. 2001; 33:811-824. https://doi.org/10.1006/jmcc.2001.1353. PMid:11273733.
  • Graettinger JS, Muensterm JJ, Sekverstone IA, Campbell JA. A correlation of clinical and hemodynamic studies in patients with hyperthyroidism with and without congestive heart failure. Journal of Clinical Investigation. 1959; 38(8):1316-1327. https://doi.org/10.1172/JCI103906. PMid:13673087 PMCid:PMC442085.
  • Theilen EO, Wilson WB. Hemodynamic effects of peripheral vasoconstriction in normal and thyrotoxic subjects. Journal of Applied Physiology. 1967; 22(2):207-210. https://doi. org/10.1152/jappl.1967.22.2.207. PMid:6017884.
  • deGroot WJ, Leonard JJ. Hyperthyroidism as a high cardiac output state. American Heart Journal. 1970; 79(2):265-275. https://doi.org/10.1016/0002-8703(70)90318-2.
  • Anthonisen P, Hoist E, Thomson AA Chr. Determination of cardiac output and other hemodynamic data in patients with hyper and hypothyroidism using dye dilution technique. Scandinavian Journal of Clinical Lab Investigation. 1960; 12(4):472-480. https://doi. org/10.3109/00365516009065412, PMid:13683720.
  • Resnick LM, Laragh JH. Plasma renin activity in syndrome of thyroid hormone excess and deficiency. Life Sciences. 1982; 30(7-8):585-586. https://doi.org/10.1016/0024- 3205(82)90273-9.
  • Klein I, Levey GS. Unusual manifestations of hypothyroidism. Archives of Internal Medicine. 1984; 144(1):123-128. https://doi.org/10.1001/archinte.1984.00350130143025. PMid:6229226.
  • Mintz G, Pizzarello R, Klein I. Enhanced left ventricular diastolic function in hypothyroidism, noninvasive assessment and response to treatment. Journal of Clinical Endocrinology & Metabolism. 1991; 73(1):146-150. https:// doi.org/10.1210/jcem-73-1-146. PMid:2045465.
  • Kahaly GJ, Wagner S, Nieswandt J, et al. Stress echocardiography in hyperthyroidism. Journal of Clinical Endocrinology and Metabolism. 1999; 84(7):2308-2313. https://doi.org/10.1210/jcem.84.7.5830. PMid:10404794.
  • Biondi B, Palmieri EA, Lombardi G, Fazio S. Effect of thyroid hormone on cardiac function, the relative importance of heart rate, loading conditions and myocardial contractility in the regulation of cardiac performance in human hypothyroidism. Journal of Clinical Endocrinology and Metabolism. 2002; 87(3):968-974. https://doi.org/10.1210/ jcem.87.3.8302. PMid:11889145.
  • Magner J, Clark W, Allenby P. Congestive heart failure and sudden death in young women with thyrotoxicosis. Western Journal of Medicine. 1988; 149(1):86-91.
  • Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Annals of Internal Medicine. 2002; 137(11):904-914. https:// doi.org/10.7326/0003-4819-137-11-200212030-00011. PMid:12458990.
  • Biondi B, Fazio S, Carella C, et al. Cardiac effects of long term thyrotropin suppressive therapy with levothyroxine. Journal of Clinical Endocrinology and Metabolism. 1993; 77(2):334-338. https://doi.org/10.1210/jcem.77.2.8345037. PMid:8345037.
  • Biondi B, Fazio S, Carella C, et al. Control of adrenergic over activity by B blockade improves quality of life in patients receiving long term supportive therapy with levothyroxine. Journal of Clinical Endocrinology and Metabolism. 1994; 78(5):1028-1033. https://doi. org/10.1210/jcem.78.5.8175955. PMid: 8175955.
  • Biondi B, Fazio S, Cuocolo A, et al. Impaired cardiac reserve and exercise capacity in patients receiving longterm thyrotropin suppressive therapy with levothyroxine. Journal of Clinical Endocrinology and Metabolism. 1996; 81:4224-4228. https://doi.org/10.1210/jcem.81.12.8954019. PMid:8954019.
  • Biondi B, Palmieri EA, Fazio S, et al. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middleaged patients. Journal of Clinical Endocrinology and Metabolism. 2000; 85(12):4702-4705. https://doi. org/10.1210/jcem.85.12.7085. PMid: 11134131.
  • Fazio S, Biondi B, Carella C, et al. Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine beneficial effect of betablockade. Journal of Clinical Endocrinology and Metabolism. 1995; 80(7):2222-2226. https://doi. org/10.1210/jcem.80.7.7608283. PMid: 7608283.
  • Ching GW, Franklyn JA, Stallard TJ, et al. Cardiac hypertrophy as a result of long term thyroxine therapy and thyrotoxicosis. Heart. 1996; 75(4):363-368. https:// doi.org/10.1136/hrt.75.4.363. PMid:8705762 PMCid: PMC484311
  • Shapiro IE, Sievert R, Ong I, et al. Minimal cardiac effects in asymptomatic athyrocotic patients chronically treated with thyrotropin-suppressive doses of L-thyroxine. Journal of Clinical Endocrinology and Metabolism. 1997; 82(8):2592- 2595. https://doi.org/10.1210/jcem.82.8.4155.
  • Mercuro G, Panzuto MG, Bina A, et al. Cardiac function, physical exercise capacity and quality of life during long term thyrotropin-suppressive therapy with levothyroxine. Effects of individual dose tailoring. Journal of Clinical Endocrinology and Metabolism. 2000; 85(1):159-164. https://doi.org/10.1210/jcem.85.1.6298. PMid:10634380.
  • Klein I. Thyroxine-induced cardiac hypertrophy: time course of development and inhibition by propranolol. Endocrinology. 1988; 123(1):203-210. https://doi. org/10.1210/endo-123-1-203. PMid:2968237.
  • Parle HV, Maisonnenve P, Sheppard MC, et al. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: A 10-year cohort study. Lancet. 2001; 358(9285):861-865. https://doi. org/10.1016/S0140-6736(01)06067-6.
  • Sawin CT, Geller A, Wolf PA. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. New England Journal of Medicine. 1994; 331(19):1249-1254. https://doi.org/10.1056/ NEJM199411103311901. PMid:7935681.
  • Auer J, Scheibuer P, Mische T, et al. Subclinical hyperthyroidism as a risk factor for atrial fibrillation. American Heart Journal. 2001; 142(5):838-842. https://doi. org/10.1067/mhj.2001.119370. PMid:11685172.
  • Petersen P, Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke. 1988; 19():15-18. https://doi. org/10.1161/01.STR.19.1.15. PMid:3336898.
  • Haider AW, Larson MG, Benjamin EJ, Levy D. Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death. Journal of American College of Cardiology. 1998; 32(5):1454-1459. https://doi. org/10.1016/S0735-1097(98)00407-0.
  • Greenland P, Davigius ML, Dyer AR. Resting heart rate is a risk factor for cardiovascular and non-cardiovascular mortality: the Chicago Heart Association Detection Project in Industry. American Journal of Epidemiology. 1999; 149(9):853-862. https://doi.org/10.1093/oxfordjournals. aje.a009901. PMid:10221322.
  • de Llyod A, Bursell J, Gregory JW, et al. TSH receptor activation and body composition. Journal of Endocrinology. 2010; 204():13-20. https://doi.org/10.1677/JOE-09-0262. PMid:19759194.
  • Drvota V, Jansen A, Norman C, et al. Evidence for the presence of functional thyrotropin receptor in cardiac muscle. Biochemical and Biophysical Research Communications. 1995; 211(2):426-431. https://doi. org/10.1006/bbrc.1995.1831. PMid:7794253.
  • Koshiyama H, Sellitti DF, Akamizu, T, et al. Cardiomyopathy associated with Graves’ disease. Clinical Endocrinology (Oxford). 1996; 45(1):111-116. https://doi. org/10.1111/j.1365-2265.1996.tb02068.x.
  • Otto E, Forster G, Kuhlemann K, et al. TSH receptor in endocrine autoimmunity. Clinical and Experimental Rheumatology. 1996; 14 Suppl:S77-84.
  • Sellitti DF, Hill R, Dol SQ, et al. Differential expression of thyrotropin receptor mRNA in the porcine heart. Thyroid. 1997; 7(4):641-646. https://doi.org/10.1089/thy.1997.7.641. PMid:9292956.
  • Huang W, Xu J, Jing F, et al. Functional thyrotropin receptor expression in the ventricle and the effects on ventricular BNP secretion. International Journal of Basic and Clinical Endocrinology. 2014; 46(2):328-339. https://doi. org/10.1007/s12020-013-0052-6. PMid:24065308.
  • Salvatore D, Bartha T, Harney JW, Larsen PR. Molecular biological and biochemical characterization of the human type-2 selenodeiodinase. Endocrinology. 1996; 137(8):3308-3315. https://doi.org/10.1210/ endo.137.8.8754756. PMid:8754756.
  • Croteau W, Davey JC, Galton VA, St Germain DL. Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. Journal of Clinical Investigation. 1996; 98(2):405-417. https://doi.org/10.1172/ JCI118806. PMid:8755651 PMCid:PMC507444.
  • Everts ME, Verhoeven FA, Bezstarosti KK, et al. Uptake of thyroid hormones in neonatal rat cardiac myocytes. Endocrinology. 1996; 137(10):4235-4242. https://doi. org/10.1210/endo.137.10.8828482. PMid:8828482.
  • Sap J, Munoz A, Damm K, et al. The c-erb-A protein is a high affinity receptor for thyroid hormone. Nature. 1986; 324(6098):635-640. https://doi.org/10.1038/324635a0. PMid:2879242.
  • Weinberger C, Thompson CC, Ong ES, et al. The c-erb A gene encodes a thyroid hormone receptor. Nature. 1986; 324(6098):641-646. https://doi.org/10.1038/324641a0. PMid:2879243.
  • Lazar MA. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocrine Reviews. 1993; 14(2):184-193. https://doi.org/10.1210/edrv-14-2-184, PMid:8325251.
  • Plateroti M, Gauthier K, Domom-Dell C, et al. Functional interference between thyroid hormone receptor alpha (TR alpha) and natural truncated TR alpha isoforms in the control of intestine development. Molecular and Cellular Biology. 2001; 21(14):4761-4772. https://doi. org/10.1128/MCB.21.14.4761-4772.2001. PMid:11416151 PMCid:PMC87160.
  • Ladenson PW. The heart and thyroid disease. Mount Sinai Journal of Medicine. 1996; 63:118-125.
  • Ladenson PW, Kieffer JD, Farwell AP, Ridgway WC. Modulation of myocardial L-triiodithyronine receptors in normal, hypothyroid and hyperthyroid rats. Metabolism. 1986; 35(1):5-12. https://doi.org/10.1016/0026- 0495(86)90088-0.
  • Dillmann WH. Biochemical basis of thyroid hormone action in the heart. American Journal of Medicine. 1990; 88(6):626-630. https://doi.org/10.1016/0002- 9343(90)90530-Q.
  • Klein I. Thyroid hormone and cardiovascular system. American Journal of Medicine. 1990; 88(6):631-637. https://doi.org/10.1016/0002-9343(90)90531-H.
  • Davies MJ, Moore BP, Braimbridge MV. The floppy mitral valve. Study of incidence of pathology, complications in surgical necropsy and forensic material. British Heart Journal. 1978; 40(5):468-481. https://doi.org/10.1136/ hrt.40.5.468. PMid:656211 PMCid:PMC483431.
  • Hansen C, Otto E, Kuhlemann K, Forster G. Glycosaminoglycans in autoimmunity. Clinical and Experimental Rheumatology. 1996; 14(Suppl 15):59-68.
  • Hansen C, Fraiture B, Rouhi R, et al. HPLC glycosaminoglycan analysis in patients with Graves’ disease. Clinical Sciences. 1997; 92(5):511-517.
  • Kahaly G, Forster G, Hansen C. Glycosaminoglycans in thyroid eye disease. Thyroid. 1998; 8(5):429-432. https:// doi.org/10.1089/thy.1998.8.429. PMid:9623737.
  • Channick BJ, Adlin EV, Marks AD, et al. Hyperthyroidism and mitral valve prolapse. New England J Medicine. 1981; 305:497-500. https://doi.org/10.1056/ NEJM198108273050906. PMid:7254298.
  • Marks AD, Channick BJ, Adlin EV, et al. Chronic thyroiditis and mitral valve prolapse. Annals of Internal Medicine. 1985; 102:479-483. https://doi.org/10.7326/0003-4819- 102-4-483. PMid:3838425
  • Kahaly GJ, Wolfgang H, Dillmann WH. Thyroid hormone action in the heart. Endocrine Reviews. 2005; 26(5):704- 728. https://doi.org/10.1210/er.2003-0033. PMid:15632316.
  • Alonso H, Fernandez-Ruocco M, Gallego LL, et al. Thyroid stimulating hormone directly modulates cardiac electrical activity. Journal of Molecular and Cellular Cardiology. 2015; 89(B):280-286. https://doi.org/10.1016/j. yjmcc.2015.10.019. PMid:26497403.
  • Le Bouter S, Demolombe A, Chambellian C, et al. Microarray analysis reveals complex remodeling of cardiac ion channel expression with altered thyroid status: Relation to cellular and integrated electrophysiology. Circulation and Respiration. 2003; 92(2):234-242. https://doi.org/10.1161/01.RES.0000053185.75505.8E. PMid:12574152.
  • Yang T, Snyders DJ, Roden DM, Rapid inactivation determines the rectification and (K+)o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circulation and Respiration. 1997; 80(6):782-789. https://doi.org/10.1161/01.RES.80.6.782. PMid:9168780.

Abstract Views: 168

PDF Views: 0




  • An Overview of Influence of Thyroid Hormones on Cardiovascular Function

Abstract Views: 168  |  PDF Views: 0

Authors

Peranaidu Govindarajulu
Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras-Taramani Campus, Chennai − 600113, Tamil Nadu., India

Abstract


It has been very clearly established that thyroid hormones have a specific influence on cardio-vascular system. Hyper- or hypothyroidism induces cardiovascular disorders, atrial and ventricular arrhythmias, atherosclerotic vascular diseases, dyslipidemia and heart failure. Heart failure results from the impairment of ability of the ventricle to fill with or eject blood. Thyroid hormones contribute to cardiovascular events by directly acting on the cardiomyocyte via genomic and nongenomic pathways. Thyroid hormones play a critical role in maintaining cardiac homeostasis. Fluctuations in thyroid hormones due to hyper- or hypothyroidism has an adverse effect on the heart. Thyroid hormones have a direct influence on myocardial contractility, systolic and diastolic blood pressure, heart rate, heart mass, ejection fraction and heart output. Hyperthyroidism stimulates high cardiac output with low systemic vascular resistance and is associated with faster heart rate and increased left ventricular systolic and diastolic function and supraventricular atrial fibrillation. Hypothyroidism has an opposite effect on the heart rate and myocardial contractility. Hypothyroidism reduces cardiac repolarizing of K<sup>+</sup> currents such as transient outward potassium current and increase in L-type calcium current. Alterations in Thyroid Stimulating Hormone level bring about cardiac electrical disturbances. Subclinical hypothyroidism is associated with increased heart rate, atrial arrhythmias, LV mass and impaired ventricular relaxation, and increased risk of mortality due to cardio-vascular impairment. In this overview, with the available information and publications, the physiological and patho-physiological relationships between thyroid hormones and the cardiovascular system are discussed.

Keywords


Cardiovascular System, Hyperthyroidism, Hypothyroidism, Smooth Muscle Cells of the Vascular System, Subclinical Hypothyroidism, Thyroid Hormones, Thyroid Hormone Receptors, Thyroid Stimulating Hormone, Ventricular Contractions

References





DOI: https://doi.org/10.18519/jer%2F2021%2Fv25%2F215517