Many of the manifestations of thyroid disease result from alterations in cardiovascular physiology.
Various mechanisms have been suggested to explain the cardiovascular effects of thyroid hormones, including increased number and/or affinity of adrenergic receptors, alterations in intracellular signalling and adrenergic effects of thyroid hormone metabolites.1 Although the exact mechanism is uncertain, the clinical findings are indisputable.
The thyroid gland secretes thyroxine (T4) and triiodothyronine (T3) in response to a pituitary-driven stimulus, thyrotropin (thyroid-stimulating hormone or TSH). The secreted T4 is deiodinated in peripheral tissues to T3, which is the active form. Cardiac tissue lacks the capacity to deiodinate T4, so circulating T3 has a direct effect on the heart.
Thyroxine increases resting heart rate and left ventricular contractility. T3 causes decreased systemic vascular resistance (SVR) by a direct effect on the arteriolar smooth muscle cells. T3 also increases circulating blood volume by direct stimulation of erythropoietin synthesis leading to increased red cell mass, and increased renal sodium retention secondary to activation of the renin-angiotensin system in response to decreased SVR. These changes result in an increase in preload.
T3 also helps to maintain functional integrity of the vascular endothelium by inducing nitric oxide synthesis.
Cardiovascular changes in hyperthyroidism
An excess of thyroid hormones increases cardiac contractility and resting heart rate (see box below).
Cardiac output may increase by 50-300 per cent as a result of the combined effect of increases in resting heart rate, contractility, ejection fraction and blood volume, with a concomitant decrease in SVR. Cardiac arrhythmias are invariably supraventricular in origin.
The hyperdynamic circulation at rest impairs the increase of cardiac output during exercise, resulting in exertional dyspnoea. Angina may occur in patients with existing coronary artery disease and those at high risk, and congestive heart failure may occur with structural cardiac disease.
A return to the euthyroid state with treatment results in reversal of these effects.
Cardiovascular changes in hypothyroidism
Hypothyroidism results are a mirror image of the cardiovascular symptoms and signs in hyperthyroidism.
Cardiac output is reduced, owing to decreases in heart rate and stroke volume. SVR is increased, with a reduction in blood volume, resulting in a narrow pulse pressure and reduced tissue perfusion.
In severe cases there may be a fibrinous pericardial effusion. Hypothyroidism results in elevated LDL (reduced hepatic clearance) and apolipoprotein B levels in up to 90 per cent of patients. CRP and diastolic BP may rise and contribute to an increased risk of coronary atherosclerosis.
Replacement therapy with levothyroxine should be initiated in all patients to achieve a TSH level of 0.5-2.0pmol/L.
In older patients with a higher risk of coronary artery disease, a lower starting dose and a slower titration rate is advised, although evidence to suggest that replacement precipitates coronary artery disease is poor.
AF and thyroid disease
Patients with AF have a higher incidence of hyperthyroidism.2 The prevalence of AF rises from 1-8 per cent in the general population, to 10-15 per cent in hyperthyroidism, although this may be decreasing because of earlier detection and treatment.
In AF secondary to hyperthyroidism, ventricular rate control is best achieved by the non-selective beta-blocker propranolol or the selective atenolol. Oral calcium-channel blockers may be used if beta-blockers are contraindicated.3
The AHA/ACC guidelines4 on AF identify thyrotoxicosis as a weak risk factor for thromboembolic events, so warfarin is not routinely recommended.
The need for anticoagulation should be assessed individually by a specialist.
In the absence of structural heart disease, hypertension or other risk factors for thromboembolism, the benefits of anticoagulation therapy may be modest in patients under 75 years. Low-dose aspirin may be considered in all patients.
Treatment with antithyroid drugs or radioactive iodine should be initiated, and most people who are treated successfully return to sinus rhythm in two to three months. In older patients and long-standing AF, reversion to AF is less easily achieved.
|Physical signs||Systolic hypertension
Narrow pulse pressure
Left ventricular hypertrophy
Prolonged PR/QT intervals
Second/third degree heart block
T wave abnormalities
Low-voltage ECG (pericardial effusion)
|Blood tests||Increased serum cholesterol
Amiodarone and thyroid disease
Amiodarone, a class III antiarrhythmic agent, is widely used in atrial and ventricular rhythm disturbances. The high iodine content of amiodarone (3mg iodine per 100mg amiodarone) can result in hypothyroidism (5-25 per cent of treated patients) or hyperthyroidism (2-10 per cent).5
The baseline serum TSH, free T4 and T3, and antithyroid antibodies should be measured before starting amiodarone and monitored every six months.
Amiodarone-induced hyperthyroidism is described as type-1 in patients with existing thyroid disease or goitre and type-2 in euthyroid patients. Hypothyroidism should be treated with thyroxine replacement.
Treatment of both types of amiodarone-induced hyperthyroidism is more difficult. It is relatively resistant to the thio-ureas owing to high intrathy-roid iodine content, and the effect of radioactive iodine is poor because iodine uptake by the thyroid is reduced.
A pragmatic approach is to treat patients with high-dose carbimazole. Resistance to carbimazole should raise the possibility of type-2 disease.
Treatment with potassium perchlorate, with or without oral prednisolone 30-40mg per day, should be considered.
Refractory cases may need thyroidectomy.
Subclinical thyroid dysfunction
A recent meta-analysis revealed a 50 per cent increase in the risk of coronary artery disease at baseline and a 20 per cent increase at follow-up in patients with subclinical hypothyroidism.6
By contrast, subclinical hyperthyroidism is not associated with increased coronary artery disease or cardiovascular mortality.
A study of more than 2,000 patients aged over 60 years revealed that decreased TSH levels were associated with a threefold increased risk of AF.7
- Dr Iqbal is a specialist registrar in endocrinology and Dr Krishnan is a specialist registrar in cardiology, Liverpool.
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7. Sawin CT, Geller A, Wolf PA et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331(19): 1249-52.