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. 1996 Apr;75(4):363–368. doi: 10.1136/hrt.75.4.363

Cardiac hypertrophy as a result of long-term thyroxine therapy and thyrotoxicosis.

G W Ching 1, J A Franklyn 1, T J Stallard 1, J Daykin 1, M C Sheppard 1, M D Gammage 1
PMCID: PMC484311  PMID: 8705762

Abstract

OBJECTIVES: To define the effects of long-term thyroxine treatment upon heart rate, blood pressure, left ventricular systolic function, and left ventricular size, as well as indices of autonomic function, and to compare findings with those in patients with thyrotoxicosis before and during treatment. DESIGN: Cross sectional study of patients prescribed thyroxine long term (n = 11), patients with thyrotoxicosis studied at presentation (n = 23), compared with controls (n = 25); longitudinal study of patients with thyrotoxicosis studied at presentation and serially after beginning antithyroid drug treatment (n = 23). METHODS: 24 h ambulatory monitoring of pulse and blood pressure, echocardiography, forearm plethysmography, and autonomic function tests. RESULTS: Long-term thyroxine treatment in doses that reduced serum thyrotrophin to below normal had no effect on blood pressure, heart rate, left ventricular systolic function or stroke volume index, but was associated with an 18.4% increase in left ventricular mass index (mean (SEM) 101.9 (3.09) g/m2 v controls 86.1 (4.61), P < 0.01). Thryoxine treatment, like thyrotoxicosis, had no effect on tests of autonomic function. Untreated thyrotoxicosis resulted in pronounced changes in systolic and diastolic blood pressure and an increase in heart rate during waking and sleep. Patients with thyrotoxicosis at presentation had an increase in left ventricular systolic function (ejection fraction 70.5 (1.66)% v 65.4 (1.79), P < 0.01; fractional shortening 40.4 (1.54)% v 35.6 (1.46), P < 0.01), increased stroke volume index (45.9 (2.4) ml/m2 v 36.6 (1.7), P < 0.001), and an increase in forearm blood flow, and decrease in vascular resistance. They had a similar degree of left ventricular hypertrophy to that associated with thyroxine treatment (99.3 (4.03) g/m2); all changes were corrected within 2 months by antithyroid drugs. CONCLUSIONS: The development of left ventricular hypertrophy in patients receiving thyroxine in the absence of significant changes in heart rate, blood pressure, and left ventricular systolic function is consistent with a direct trophic effect of thyroid hormone on the myocardium. The presence of left ventricular hypertrophy determines that further studies are essential to assess cardiovascular risk in patients taking thyroxine long term.

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Selected References

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  1. Bilezikian J. P., Loeb J. N. The influence of hyperthyroidism and hypothyroidism on alpha- and beta-adrenergic receptor systems and adrenergic responsiveness. Endocr Rev. 1983 Fall;4(4):378–388. doi: 10.1210/edrv-4-4-378. [DOI] [PubMed] [Google Scholar]
  2. Biondi B., Fazio S., Carella C., Amato G., Cittadini A., Lupoli G., Saccà L., Bellastella A., Lombardi G. Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine. J Clin Endocrinol Metab. 1993 Aug;77(2):334–338. doi: 10.1210/jcem.77.2.8345037. [DOI] [PubMed] [Google Scholar]
  3. Bond B. R., Fox P. R., Peterson M. E., Skavaril R. V. Echocardiographic findings in 103 cats with hyperthyroidism. J Am Vet Med Assoc. 1988 Jun 1;192(11):1546–1549. [PubMed] [Google Scholar]
  4. Casale P. N., Devereux R. B., Milner M., Zullo G., Harshfield G. A., Pickering T. G., Laragh J. H. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med. 1986 Aug;105(2):173–178. doi: 10.7326/0003-4819-105-2-173. [DOI] [PubMed] [Google Scholar]
  5. Cohen M. V., Schulman I. C., Spenillo A., Surks M. I. Effects of thyroid hormone on left ventricular function in patients treated for thyrotoxicosis. Am J Cardiol. 1981 Jul;48(1):33–38. doi: 10.1016/0002-9149(81)90569-5. [DOI] [PubMed] [Google Scholar]
  6. Dillmann W. H. Biochemical basis of thyroid hormone action in the heart. Am J Med. 1990 Jun;88(6):626–630. doi: 10.1016/0002-9343(90)90530-q. [DOI] [PubMed] [Google Scholar]
  7. Feldman T., Borow K. M., Sarne D. H., Neumann A., Lang R. M. Myocardial mechanics in hyperthyroidism: importance of left ventricular loading conditions, heart rate and contractile state. J Am Coll Cardiol. 1986 May;7(5):967–974. doi: 10.1016/s0735-1097(86)80213-3. [DOI] [PubMed] [Google Scholar]
  8. Forfar J. C., Muir A. L., Sawers S. A., Toft A. D. Abnormal left ventricular function in hyperthyroidism: evidence for a possible reversible cardiomyopathy. N Engl J Med. 1982 Nov 4;307(19):1165–1170. doi: 10.1056/NEJM198211043071901. [DOI] [PubMed] [Google Scholar]
  9. GRAETTINGER J. S., MUENSTER J. J., CHECCHIA C. S., GRISSOM R. L., CAMPBELL J. A. A correlation of clinical and hemodynamic studies in patients with hypothyroidism. J Clin Invest. 1958 Apr;37(4):502–510. doi: 10.1172/JCI103631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jennings P. E., O'Malley B. P., Griffin K. E., Northover B., Rosenthal F. D. Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case for "tissue thyrotoxicosis". Br Med J (Clin Res Ed) 1984 Dec 15;289(6459):1645–1647. doi: 10.1136/bmj.289.6459.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klein I., Ojamaa K. Thyroid hormone and the cardiovascular system: from theory to practice. J Clin Endocrinol Metab. 1994 May;78(5):1026–1027. doi: 10.1210/jcem.78.5.8175954. [DOI] [PubMed] [Google Scholar]
  12. Kronik G., Slany J., Mösslacher H. Comparative value of eight M-mode echocardiographic formulas for determining left ventricular stroke volume. A correlative study with thermodilution and left ventricular single-plane cineangiography. Circulation. 1979 Dec;60(6):1308–1316. doi: 10.1161/01.cir.60.6.1308. [DOI] [PubMed] [Google Scholar]
  13. Levey G. S., Klein I. Catecholamine-thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism. Am J Med. 1990 Jun;88(6):642–646. doi: 10.1016/0002-9343(90)90533-j. [DOI] [PubMed] [Google Scholar]
  14. Littler W. A., Ireland M. A. Arterial response to venous occlusion in normotensive and hypertensive subjects. Cardiovasc Res. 1986 Feb;20(2):124–126. doi: 10.1093/cvr/20.2.124. [DOI] [PubMed] [Google Scholar]
  15. Littler W. A., Stallard T. J., Rowlands D. B. Forearm haemodynamics and blood pressure variability in hypertensive patients. Cardiovasc Res. 1988 Apr;22(4):287–290. doi: 10.1093/cvr/22.4.287. [DOI] [PubMed] [Google Scholar]
  16. Martin W. H., 3rd, Spina R. J., Korte E. Effect of hyperthyroidism of short duration on cardiac sensitivity to beta-adrenergic stimulation. J Am Coll Cardiol. 1992 May;19(6):1185–1191. doi: 10.1016/0735-1097(92)90322-e. [DOI] [PubMed] [Google Scholar]
  17. McLeay R. A., Stallard T. J., Watson R. D., Littler W. A. The effect of nifedipine on arterial pressure and reflex cardiac control. Circulation. 1983 May;67(5):1084–1090. doi: 10.1161/01.cir.67.5.1084. [DOI] [PubMed] [Google Scholar]
  18. Mintz G., Pizzarello R., Klein I. Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment. J Clin Endocrinol Metab. 1991 Jul;73(1):146–150. doi: 10.1210/jcem-73-1-146. [DOI] [PubMed] [Google Scholar]
  19. Nixon J. V., Anderson R. J., Cohen M. L. Alterations in left ventricular mass and performance in patients treated effectively for thyrotoxicosis. A comparative echocardiographic study. Am J Med. 1979 Aug;67(2):268–276. doi: 10.1016/0002-9343(79)90402-9. [DOI] [PubMed] [Google Scholar]
  20. Parle J. V., Franklyn J. A., Cross K. W., Jones S. R., Sheppard M. C. Thyroxine prescription in the community: serum thyroid stimulating hormone level assays as an indicator of undertreatment or overtreatment. Br J Gen Pract. 1993 Mar;43(368):107–109. [PMC free article] [PubMed] [Google Scholar]
  21. Polikar R., Burger A. G., Scherrer U., Nicod P. The thyroid and the heart. Circulation. 1993 May;87(5):1435–1441. doi: 10.1161/01.cir.87.5.1435. [DOI] [PubMed] [Google Scholar]
  22. Richelsen B., Sørensen N. S. Alpha 2- and beta-adrenergic receptor binding and action in gluteal adipocytes from patients with hypothyroidism and hyperthyroidism. Metabolism. 1987 Nov;36(11):1031–1039. doi: 10.1016/0026-0495(87)90022-9. [DOI] [PubMed] [Google Scholar]
  23. Roti E., Minelli R., Gardini E., Braverman L. E. The use and misuse of thyroid hormone. Endocr Rev. 1993 Aug;14(4):401–423. doi: 10.1210/edrv-14-4-401. [DOI] [PubMed] [Google Scholar]
  24. Rowlands D. B., Glover D. R., Ireland M. A., McLeay R. A., Stallard T. J., Watson R. D., Littler W. A. Assessment of left-ventricular mass and its response to antihypertensive treatment. Lancet. 1982 Feb 27;1(8270):467–470. doi: 10.1016/s0140-6736(82)91448-9. [DOI] [PubMed] [Google Scholar]
  25. Sawin C. T., Geller A., Wolf P. A., Belanger A. J., Baker E., Bacharach P., Wilson P. W., Benjamin E. J., D'Agostino R. B. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. 1994 Nov 10;331(19):1249–1252. doi: 10.1056/NEJM199411103311901. [DOI] [PubMed] [Google Scholar]
  26. Teichholz L. E., Kreulen T., Herman M. V., Gorlin R. Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol. 1976 Jan;37(1):7–11. doi: 10.1016/0002-9149(76)90491-4. [DOI] [PubMed] [Google Scholar]
  27. Thyroxine replacement therapy. Lancet. 1991 Jan 19;337(8734):171–172. [PubMed] [Google Scholar]
  28. West J. N., Townend J. N., Davies P., Sheridan J. J., Stallard T. J., Davies M. K., Littler W. A. Effect of unrestricted activity on accuracy of ambulatory blood pressure measurement. Hypertension. 1991 Nov;18(5):593–597. doi: 10.1161/01.hyp.18.5.593. [DOI] [PubMed] [Google Scholar]
  29. Woeber K. A. Thyrotoxicosis and the heart. N Engl J Med. 1992 Jul 9;327(2):94–98. doi: 10.1056/NEJM199207093270206. [DOI] [PubMed] [Google Scholar]

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