The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism


  • Milena S. Pandrc Department of Cardiology, Military Medical Academy, Belgrade
  • Andjelka Ristić Department of Urgent Internal Medicine, Military Medical Academy, Belgrade
  • Vanja Kostovski Clinic for Thoracic Surgery, Military Medical Academy, Belgrade
  • Jelena Milin-Lazović Institute for Medical Statistics and Informatics, Clinical Center of Serbia, Belgrade
  • Nataša Milić 1. Institute for Medical Statistics and Informatics, Clinical Center of Serbia, Belgrade, Serbia; 2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America
  • Jasmina Ćirić Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, School of Medicine University of Belgrade, Belgrade


subclinical hypothyroidism, electrocardiography, echocardiography


Paper description:

Clarification of the effects of levothyroxine treatment on cardiovascular risk present in subclinical hypothyroidism may contribute to the strategy in planning cardiovascular preventive treatments.

• We examined whether treatment of subclinical hypothyroidism by levothyroxine has any effect on cardiac morphology and function estimated by standard electrocardiographic and echocardiographic indicators.

• Our results suggest a subtle improvement of cardiac structure and function.

• The study supports electrocardiographic and echocardiographic evaluation for monitoring the therapeutic effect of levothyroxine. This could also be an objective approach when deciding whether a patient should be treated permanently after the trial period.

Abstract: Current controversies related to the treatment of subclinical hypothyroidism (SCH) with thyrotropin (TSH) < than 10 mU/L are based on the lack of evidence that levothyroxine therapy has beneficial effects. The aim of our study is to estimate the effect of levothyroxine treatment on cardiac morphology and function in subclinical hypothyroidism. Body mass index, waist circumference, blood pressure, electrocardiographic and standard echocardiographic parameters were measured before levothyroxine therapy and 3 months after TSH normalization. Significant reduction in systolic and diastolic blood pressure, PR, QT and QT corrected intervals, as well as increase in heart rate were recorded in the group on levothyroxine therapy. The following parameters of the left and right ventricle were significantly decreased in the treatment group: left ventricular mass index and volume, systolic and diastolic time intervals, and mitral annular plane systolic excursion (MAPSE). The increase was recorded as fractional shortening and pressure rise in early systole (dP/dt), right atrial wall thickness and diameters. Our study did not confirm differences in basic echocardiographic parameters between the treated and control groups, apart from an echocardiographic improvement of cardiac structure and function in treated individuals. The findings suggest electrocardiographic and echocardiographic screening in monitoring the therapeutic effect.

Received: October 29, 2019; Revised: January 5, 2020; Accepted: February 11, 2020; Published online: February 19, 2020

How to cite this article: Pandrc MS, Ristić A, Kostovski V, Milin-Lazović J, Milić N, Ćirić J. The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism. Arch Biol Sci. 2020;72(1):137-46.


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Van Vliet G, Deladoëy J. Interpreting minor variations in thyroid function or Echostructure: Treating Patients, Not Numbers or Images. Pediatr Clin North Am. 2015;62(4):929-42.

Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Evans JG, Hasan DM, Rodgers H, Tunbridge FK. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham survey. Clin Endocrinol (Oxf) 1991;43:55-69.

Razvi S, Weaver JU, Vanderpump MP, Pearce SHS. The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham survey cohort. J Clin Endocrinol Metab, 2010;95:1734-40.

Pearce SHS, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, Wemeau JL. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013;2:215-28.

Pandrc M, Ristić A, Kostovski V, Stanković M, Antić V, Milin-Lazović J, Ćirić J. The effect of the early substitution of subclinical hypothyroidism on biochemical blood parameters and the quality of life. J Med Biochem. 2017;36:127-36.

Pandrc M S, Ristić A, Kostovski V, Randjelović-Krstić V, Milin-Lazović J, Nedeljković-Beleslin B, Ćirić J. Evaluation of a three-month trial of thyroxine replacement in symptomatic subclinical hypothyroidism: the impact on clinical presentation, quality of life and adoption of long-term therapy. Vojnosanit Pregl. 2020;

Pyati A, Dhuttargi S, Das D. Assessment of the Cardiovascular Risk in Subclinical Hypothyroidism. Int J Pharm Biol Sci. 2012;2(2):128-34.

Kottagi SS, Rathi DB, Dongre NN. Evaluation of LDLCholesterol / HDL-Cholesterol Ratio as Predictor of Dyslipidemia in Subclinical Hypothyroidism. J Krishna Inst Medical Sci Univ. 2014;3(1):34-40.

Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam study. Ann Int Med. 2000;132:270-8.

Walsh JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, Michelangeli V. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med. 2005;165:2467-72.

Feldt-Rasmussen U. Subclinical Hypothyroidism and Cardiovascular Risk - An Overview of Current Understanding. European Endocrinol. 2011;7(1):53-7.

Yao K, Zhao T, Zeng L, Yang J, Liu Y, He Q, Zou X. Non-invasive markers of cardiovascular risk in patients with subclinical hypothyroidism: A systematic review and meta-analysis of 27 case control studies. Sci Rep. 2018;8:4579.

Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med. 2002;137:904-14.

Arem R, Rokey R, Kiefe C, Escalante DA, Rodriguez A. Cardiac systolic and diastolic function at rest and exercise in subclinical hypothyroidism: effect of thyroid hormone therapy. Thyroid 1996;6:397-402.

Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, Ferrannini E. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab. 2001;86:1110-5.

Curnock AL, Dweik RA, Higgins BH, Saadi HF, Arroliga AC. High prevalence of hypothyroidism in patients with primary pulmonary hypertension. Am J Med Sci. 1999;318:289-92.

Nakova VV, Krstevska B, Kostovska ES, Vaskova O, Ismail LG. The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism. Arch Endocrinol Metab. 2018;62(4):392-8.

Sun Z, Ojamaa K, Coetzee WA, Artman M, Klein I. Effects of thyroid hormone on action potential and repolarization currents in rat ventricular myocytes. Am J Physiol Endocrinol Metab. 2000;278:E302-7.

Bargiggia GS, Bertucci C, Recusani F, Raisaro A, de Servi S, Valdes-Cruz LM, Sahn DJ, Tronconi L. A new method for estimating left ventricular dP/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization. Circulation. 1989;80:1287-92.

Kolias TJ, Aaronson K D, Armstrong FW. Doppler-derived dP/dt and −dP/dt predict survival in congestive heart failure. J Am Coll Cardiol. 2000;36(5):1594-9.

Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H, Edvardsen T. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277-314.

Klein I, Danzi S. Thyroid Disease and the Heart. Circulation. 2007;116:1725-35.

Papi G, Degli Uberti E, Betterle C, Carani C, Pearce EN, Braverman LE, Roti E. Subclinical hypothyroidism. Curr Opin Endocrinol Diabetes Obes. 2007;14:197-208.

Biondi B, Palmieri EA, Lombardi G, Fazio S. Subclinical hypothyroidism and cardiac function. Thyroid.2002;12:505-10.

Drazner MH, Rame JE, Marino EK, Gottdiener JS, Kitzman DW, Gardin JM, Manolio TA, Dries DL, Siscovick DS. Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. J Am Coll Cardiol. 2004;43:2207-15.

Gardin JM, Siscovick D, Anton-Culver H, Lynch JC, Smith VE, Klopfenstein HS, Bommer WJ, Fried L, O'Leary D, Manolio TA. Sex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study. Circulation. 1995;91:1739-48.

Yazici M, Gorgulu S, Sertbas Y, Yazici M, Gorgulu S, Sertbas Y, Uyan C. Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function. Int J Cardiol. 2004;95:135-43.

Brenta G, Mutti LA, Schnitman M, Fretes O, Perrone A, Matute ML. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism and its response to l-throxine therapy. Am J Cardiol. 2003;91:1327-30.

Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, Bonè F, Lombardi G, Saccà L. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab. 1999;84:2064 -7.

Danzi S, Klein I. Thyroid hormone and the cardiovascular system. Minerva Endocrinologica. 2004;29:139-50.

Unal O, Erturk E, Ozkan H, Kiyici S, Guclu M, Ersoy C, Yener F, Imamoglu S. Effect of Levothyroxine Treatment on QT Dispersion in Patients with Subclinical Hypothyroidism. Endocrine Practice. 2007;13(7):711-5.

Klein I. Endocrine disorders and cardiovascular disease. In: Zipes DP, Braunwald E, editors. Heart Disease: a textbook of cardiovascular. 7th ed. Philadelphia: Saunders; 2005. p. 2051-64.

Fredlund BO, Olsson SB. Long QT interval and ventricular tachycardia of “torsade de pointe” type in hypothyroidism. Acta Med Scand. 1983;213(3):231-5.

Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. Engl J Med. 2001;344:501-9.

Gao C, Li T, Liu J, Guo Q, Tian L. Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement. PLoS ONE. 2015;10(7):e0131776.

Ilić S, Tadić M, Ivanović B, Čaparević Z, Trbojević B, Čelić V. Left and right ventricular structure and function in subclinical hypothyroidism: The effects of one-year levothyroxine treatment. Med Sci Monit. 2013;19:960-8.

Dorr M, Wolff B, Robinson DM, John U, Ludemann J, Meng W, Felix SB, Völzke H. The association of thyroid function with cardiac mass and left ventricular hypertrophy. J Clin Endocrinol Metab. 2005;90:673-7.

Ripoli A, Pingitore A, Favilli B, Bottoni A, Turchi S, Osman NF, De Marchi D, Lombardi M, L'Abbate A, Iervasi G. Does subclinical hypothyroidism affect cardiac pump performance? Evidence from a magnetic resonance imaging study. J Am Coll Cardiol. 2005;45(3):439-45.

Carrick-Ranson G, Hastings JL, Bhella PS, Shibata S, Fujimoto N, Palmer MD, Boyd K, Levine BD. Effect of healthy aging on left ventricular relaxation and diastolic suction. Am J Physiol Heart Circ Physiol. 2012;303(3):H315-22.

Chen X, Zhang N, Zhang WL, Shi JP. Meta-analysis on the association between subclinical hypothyroidism and the left ventricular functions under Doppler echocardiography. Zhonghua Liu Xing Bing Xue Za Zhi. 2011;32(12):1269-74.

Doin FC, Rosa-Borges M, Martins MR, Moisés VA, Abucham. Diagnosis of subclinical central hypothyroidism in patients with hypothalamic-pituitary disease by Doppler echocardiography. Eur J Endocrinol. 2012;166:631-40.




How to Cite

Pandrc MS, Ristić A, Kostovski V, Milin-Lazović J, Milić N, Ćirić J. The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism. Arch Biol Sci [Internet]. 2020Mar.24 [cited 2022Jan.19];72(1):137-46. Available from: