Cardiovascular Effects of Thyroid Disease

By Jodi K. Sangster, DVM, David L. Panciera, DVM, MS, DACVIM (Small Animal Internal Medicine), Jonathan A. Abbott, DVM, DACVIM (Cardiology)
Original article from


Thyroid hormones have many effects on cardiovascular function, and deficiency or excess of thyroid hormones can result in cardiac dysfunction. Abnormalities of the cardiovascular system are often identified during examination of hyperthyroid and hypothyroid patients. This article addresses the effects of thyroid hormones on the cardiovascular system and the clinical relevance of the cardiovascular response to thyroid dysfunction. In addition, treatment recommendations are presented.
Thyroid hormones have an integral role in cardiovascular homeostasis, affecting myocardial function, systemic vascular resistance, endothelial function, and response to catecholamines. Clinical evidence of the influence of thyroid hormones on the cardiovascular system is most apparent in hyperthyroidism, in which tachycardia and abnormal heart sounds are frequent findings on physical examination. The cardiovascular effects of hypothyroidism are typically more subtle, but they may be clinically important in some situations. This review addresses the effects of thyroid hormones on the cardiovascular system, the clinical consequences of hyperthyroidism and hypothyroidism, and the management of these disorders.

Cardiovascular Effects of Thyroid Hormone

Thyroid hormones alter cardiovascular function directly, through effects on the heart, and indirectly, through effects on the peripheral vasculature (BOX 1). Myocardial contractility and relaxation are enhanced by the genomic actions of 3,5,3’-triiodothyronine (T3). Specifically, T3increases the expression of genes that encode ion transporters, β1-adrenergic receptors, and contractile proteins. These effects increase calcium release and reuptake from the sarcoplasmic reticulum.1 –3 The resultant increase in cytosolic calcium increases contractility, and the more rapid calcium reuptake enhances diastolic relaxation.

 Effects of Thyroid Hormone on the Heart

  • Increased myocardial contractility
    • Increased expression of contractile proteins
    • Increased numbers of β-adrenergic receptors
    • Increased calcium release from sarcoplasmic reticulum
    • Increased sodium-potassium pump activity
    • Increased membrane permeability to sodium ions
  • Enhanced myocardial relaxation via increased calcium reuptake by sarcoplasmic reticulum
  • Increased preload
    • Stimulation of erythropoietin, increasing red cell mass
    • Activation of the renin-angiotensin-aldosterone system, increasing plasma volume
  • Decreased afterload
    • Relaxation of vascular smooth muscle
    • Increased generation of nitric oxide
    • Increased locally mediated vasodilation secondary to increased metabolic rate of peripheral tissues

Nongenomic effects of T3 on cardiac myocytes include stimulation of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity, an increase in the activity of sodium-potassium pumps, recruitment of slowly inactivating membrane sodium channels,3 and an increase in membrane permeability to sodium ions.4 In hyperthyroidism, these effects may enhance myocardial function but may also predispose the patient to cardiac arrhythmias.5
In addition to direct effects on cardiac function, thyroid hormones induce important changes in the peripheral circulation (BOX 1). T3 has been shown to rapidly and directly cause relaxation of vascular smooth muscle cells,6 leading to decreased systemic vascular resistance. Generation of nitric oxide by endothelial cells is enhanced by thyroid hormones, contributing to arteriolar vasodilation in hyperthyroidism.7 In addition, thyroid hormones increase metabolic rate and oxygen demands of the peripheral tissues,3 resulting in locally mediated vasodilation. The renin-angiotensin-aldosterone system (RAAS) is activated in response to the decrease in resistance, thereby increasing plasma volume through sodium retention.8 Thyroid hormone also stimulates erythropoietin secretion,9 resulting in increased red blood cell mass.

Key Points

  • Thyroid hormones cause vasodilation, increase blood volume, and enhance myocardial contractility.
  • Clinical manifestations of feline hyperthyroidism related to the cardiovascular system include tachycardia, heart murmur, gallop rhythm, and systemic arterial hypertension.
  • Hypertension may develop before or after treatment of hyperthyroidism, necessitating ongoing monitoring of blood pressure after reestablishing a euthyroid state.
  • Congestive heart failure is uncommon in cats with hyperthyroidism and should be managed with antithyroid therapy in addition to treatment deemed appropriate for the manifestations of heart failure and specific cardiac abnormalities.
  • Hypothyroidism can result in bradycardia, decreased myocardial contractility, and, rarely, clinically significant atherosclerosis and myocardial failure.
  • Hypothyroid heart disease is largely reversible with levothyroxine supplementation.


First described in 1980, feline hyperthyroidism has become increasingly recognized and is currently the most frequently diagnosed feline endocrinopathy, with a prevalence of 2% across cats of all ages.10,11 Because of increased awareness of hyperthyroidism and routine screening of serum thyroxine (T4) concentrations in older cats, modern clinical manifestations of feline hyperthyroidism are often mild compared with early descriptions of the disease. In cats, hyperthyroidism is caused by adenomatous hyperplasia of the thyroid gland or, rarely (1% to 3% of cases), by thyroid carcinoma.12 Hyperthyroidism in dogs is much less common and is either iatrogenic13 or the result of a functional thyroid follicular carcinoma or adenocarcinoma.14 Only 10% to 20% of thyroid tumors in dogs are functional, and unlike those affecting cats, most thyroid tumors of dogs are malignant.15
Cardiovascular Effects of Hyperthyroidism
The direct cardiac effects of excess thyroid hormone include enhanced contractility and diastolic function that contribute to an increase in stroke volume. Cardiac output is increased further by positive chronotropic effects that result from heightened responsiveness to sympathetic stimulation, conferred by an increase in the number of β1-adrenergic receptors, enhanced rate of spontaneous depolarization of sinoatrial node cells,16 and reduced influence of the parasympathetic nervous system.17 –19 The reduced systemic vascular resistance induced by peripheral vasodilation and increased blood flow induced by hyperthyroidism further increase cardiac output. The resulting hemodynamic burden and altered myocardial dynamics can lead to cardiac dysfunction.
Whereas diastolic and mean arterial blood pressures are decreased and systolic pressure is increased in people with hyperthyroidism, systolic, diastolic, and mean systemic arterial pressures were all elevated in cats with experimentally induced hyperthyroidism of 2 weeks’ duration.20These findings suggest an increase, rather than a decrease, in vascular resistance, but it is unclear if similar changes are present in cats with naturally occurring hyperthyroidism. Hypertension likely results from the marked increase in cardiac output combined with expanded plasma volume caused by activation of the RAAS and expanded red cell mass caused by stimulation of erythropoietin release.21,22 However, the role of the RAAS in cats with hypertension associated with hyperthyroidism is unclear.23 Important clinical manifestations of hyperthyroidism-induced cardiac dysfunction in veterinary patients include arrhythmias, intolerance of aggressive fluid therapy or stress, hypertension, and congestive heart failure (CHF).9,18
Clinical Findings
The cardiovascular effects of hyperthyroidism are responsible for some of the most prevalent clinical findings in affected patients. Heart murmurs or gallop sounds are auscultated in 35% to 50% of affected cats, and tachycardia is found in a slightly higher proportion.24 Cardiomegaly is noted radiographically in approximately 26% to 40% of hyperthyroid cats.25 –27 Hyperthyroid cats are at increased risk for arterial thromboembolism.28
The most common electrocardiographic (ECG) abnormality in hyperthyroid cats is sinus tachycardia, detected in 34% of cases. Other ECG abnormalities include increased R-wave amplitude consistent with left ventricular enlargement (8% of patients) and left anterior fascicle block pattern (FIGURE 1) or right bundle branch block (6% to 10% of cases). In addition, arrhythmias—including atrial and ventricular premature contractions and, less frequently, atrioventricular block, atrial tachycardia, and ventricular tachycardia—may be identified.25,29 –31Increased R-wave amplitude correlates poorly with echocardiographic evidence of left ventricular enlargement.32 While not well documented, arrhythmias are expected to resolve after successful treatment of hyperthyroidism.
Abnormal echocardiographic findings are common, although usually mild, in hyperthyroid cats.33The most common echocardiographic abnormality in hyperthyroid cats is hypertrophy of the left ventricular posterior wall, identified in approximately 72% of affected cats.34 Other echocardiographic abnormalities of hyperthyroidism include left atrial enlargement in 50% of cats, increased left ventricular end-diastolic diameter in 47%, septal hypertrophy in 40%, and increased fractional shortening in 22%.26,34 Enhanced left ventricular systolic function with normal diastolic function has been documented using Doppler tissue imaging in hyperthyroid cats.35 Severe ventricular dilation with myocardial hypocontractility has also been reported.36 Eccentric hypertrophy(an increase in myocardial mass associated with an increase in ventricular volume)is expected secondary to the increase in preload and decrease in systemic vascular resistance. However, as has been reported in some human patients, concentric hypertrophy also occurs, possibly reflecting an increase in systolic wall stress.37,38 The influence of concurrent disease, such as renal dysfunction or systemic hypertension, on myocardial remodeling is unknown but could contribute to development of concentric hypertrophy in hyperthyroid cats.
It is unclear from investigations of hyperthyroid cats if eccentric or concentric hypertrophy predominates. This likely reflects the paucity of reports and the complex pathogenesis of myocardial changes, both direct and indirect, in hyperthyroidism. There is echocardiographic evidence that hyperthyroid-induced cardiac changes resolve with treatment in many cats, but they may persist in others.33,34 However, published echocardiographic data obtained after treatment of hyperthyroidism are limited, and factors that might affect resolution of cardiac changes have received little attention.
There is considerable overlap in echocardiographic findings between cats with hyperthyroidism-related concentric hypertrophy and those with hypertrophic cardiomyopathy.32 In addition, hypertension can cause left ventricular posterior wall and/or septal hypertrophy similar to changes induced by hyperthyroidism.39 Although the prevalence of asymmetric hypertrophy and perhaps systolic anterior motion of the mitral valve may be greater in patients with primary myocardial disease, echocardiography cannot reliably differentiate these conditions; therefore, thyroid function and blood pressure should be evaluated in middle-aged and older cats with cardiac abnormalities.
The prevalence of CHF in hyperthyroid cats is approximately 2%.24,40 Cats in CHF show clinical signs typical of that condition, such as dyspnea, anorexia, cyanosis, and potentially weak femoral pulses. Pleural effusion secondary to CHF can obscure the cardiac silhouette on thoracic radiographs. Pulmonary venous engorgement and a patchy interstitial or alveolar pattern resulting from pulmonary edema may also be seen (FIGURE 2A and FIGURE 2B). As in people, heart failure in hyperthyroid cats would be expected to resolve after thyroid hormone levels are controlled.41,42 However, the response to treatment of heart failure in hyperthyroid cats with concurrent primary myocardial disease is less certain.
The cardiac phenotype of hyperthyroid cats with CHF has been incompletely described; therefore, findings in people with hyperthyroidism may be relevant. Heart failure occurs in 6% of people with hyperthyroidism and is usually associated with the development of atrial fibrillation.43 Left ventricular dilation and decreased ejection fraction are found in about 50% of hyperthyroid humans with CHF. In people with hyperthyroidism and preserved left ventricular ejection fraction, CHF almost always resolves after a euthyroid state is established. Resolution of heart failure and left ventricular dysfunction after treatment of hyperthyroidism is less predictable in patients with reduced ejection fraction, although indices of systolic myocardial function return to normal in most cases.44,45
In the most detailed report of CHF in hyperthyroid cats, Jacobs et al36 described four cases of CHF characterized by pleural effusion in hyperthyroid cats, two of which died of CHF. The echocardiographic abnormalities of these cats primarily reflected severe ventricular dilation and myocardial hypocontractility rather than the ventricular hyperkinesis observed in many cases of hyperthyroid heart disease. While the poor outcome of these cases may be unusual, this case series demonstrates that hyperthyroidism can contribute to, or directly cause, severe heart disease. Other, less detailed reports of hyperthyroid cats with heart failure include those with systolic dysfunction34 as well as normal contractility.32 Because the cases with hypocontractility were reported when dilated cardiomyopathy (DCM) secondary to taurine deficiency was common, it is possible that some of these cats had concurrent hyperthyroidism and DCM. However, DCM has also been reported in people secondary to thyrotoxicosis.46
It is likely that tachycardia and other effects of hyperthyroidism are detrimental in patients with underlying primary cardiomyopathy and could cause decompensation of a previously subclinical condition. Because16% of apparently healthy cats were found to have subclinical cardiomyopathy in a 2009 study,47 hyperthyroidism and primary cardiomyopathy would be expected to coexist in a substantial number of feline patients. However, cardiac changes in hyperthyroid heart disease may be similar to those resulting from primary hypertrophic cardiomyopathy, so it is unknown how frequently hyperthyroidism complicates preexisting heart disease. Serial echocardiograms after resolution of hyperthyroidism may be the most reliable method to determine if primary cardiomyopathy is present. However, diagnosis of primary cardiomyopathy before treatment of hyperthyroidism is problematic.
The cardiac biomarker N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) has proven useful in the diagnosis of CHF in cats and has been shown to differentiate normal cats from those with occult cardiomyopathy.48 Hyperthyroidism induces an increase in NT-pro-BNP in humans49 and has been shown in a preliminary report to result in modest elevations in hyperthyroid cats.50Cardiac troponin I, an indicator of myocardial cellular damage, was elevated in some cats with hyperthyroidism in one study.51 Until these biomarkers are compared in cats with hyperthyroidism and cats with primary cardiac disease, it is not clear if they will prove useful in differentiating these disorders.
Hypertension is a common complication of hyperthyroidism in cats, and although the prevalence varies considerably depending on the population studied, it is likely to be 10% to 20%.52 –57Hypertension has been shown to persist in at least the first 4 weeks of treatment with methimazole despite normalization of thyroid hormone concentrations,58 and some cats that are normotensive before treatment may become hypertensive when euthyroid.52 Concurrent renal disease may play a role in the latter finding; approximately 15% of cats become azotemic after treatment of hyperthyroidism57 as previously subclinical renal insufficiency is unmasked. However, in one study,56 only 35% of cats that became hypertensive after treatment for hyperthyroidism were azotemic, so renal disease is likely not the sole cause of posttreatment hypertension. Blood pressure should be measured at the time of diagnosis of hyperthyroidism and after the disease has been controlled.
The clinical findings in hyperthyroid dogs are similar to those in cats, with presenting signs including panting, polyphagia, weight loss, and polyuria/polydipsia.13,59,60 Cardiovascular manifestations of canine hyperthyroidism are also similar and include tachycardia, premature ventricular contractions, increased R-wave amplitude, and hypertension.13,59 These signs, accompanied by an elevated T4 concentration, should prompt a search for a functional thyroid tumor or oversupplementation of thyroid hormone. As in cats, treatment of the hyperthyroidism resolves the cardiovascular signs.
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