THYROID DISORDERS AND
CARDIOVASCULAR DISEASE
K SRINIVAS GEN MED1 February 2015
thyroid disorders and cardiovascular disease 1
INTRODUCTION
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The thyroid gland and heart share a close relationship arising in
embryology.
The close physiologic relationship is affirmed by predictable changes in
cardiovascular function across entire range of thyroid disease states
Cardiovascular manifestations are some of the most common and
characteristic findings of hyperthyroidism
THYROID FUNCTION
TESTING
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The serum TSH level is the most widely used and sensitive measure for the
diagnosis of hypothyroidism and hyperthyroidism
Serum TSH levels increase(>5mIU/ml) in patients with primary
hypothyroidism
Serum TSH levels are low(<0.1 mIU/ml) in hyperthyroidism
Autoimmune thyroid disease can be diagnosed by measuring antithyroid
antibodies specifically antithyroid peroxidase (anti-TPO) or antithyroglobulin
antibodies
Thyroid hormone-catecholamine
interaction
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Early observations of the heart in hyperthyroidism proposed enhanced
sensitivity to catecholamines.
This postulate formed the basis for the test described by Emil Goetsch in
1918, in which hyperthyroidism could be diagnosed by demonstrating a
marked cardioacceleration and blood pressure in response to small
subcutaneous doses of epinephrine.
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Increased beta1-adrenergic receptors on cardiac myocytes observed in
experimental hyperthyroidism provide a mechanism for enhanced
catecholamine sensitivity.
Accompanying the increased levels of beta1-adrenergic receptors and
guanosine triphosphate–binding proteins, thyroid hormone decreases the
expression of cardiac-specific adenylyl cyclase catalytic subunit and thereby
maintains the cellular response to betaadrenergic agonists within normal
limits.
HYPERTHYROIDISM
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Cardiovascular symptoms are often predominant clinical presentation of
pts with hyperthyroidism
Most patients experience palpitations
HR >90/min at rest and during sleep and increase during exercise is
exaggerated.
Many pts experience exertional dyspnea and exercise intolerance
caused in part by skeletal and respiratory muscle weakness.
Some patients can experience angina like chest pain
In older pts with suspected or known CAD, the increase in cardiac work
can produce myocardial ischemia
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Rarely pts,usually young women experience chest pain at rest with
ecg changes
Cardiac catheterization has demonstrated that most of these patients
have angiographically normal coronary arteries but coronary
vasospasm can occur.
Recent reports have documented cerebrovascular ischemic symptoms
in young primarily Asian women
MOYAMOYA DISEASE, characterized by anatomic occlusion of the
terminal portions of internal carotid arteries
Hyperthyroidism is associated with substantial degree of pulmonary
hypertension(Pul. Artery systolic pressure >50 mm Hg).
ATRIAL FIBRILLATION
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The most common rhythm disturbance in patients with hyperthyroidism is
sinus tachycardia.
The prevalence of atrial fibrillation and the less common forms of
supraventricular tachycardia in this disease ranges from 2% to 20%.
When compared with a control population with normal thyroid function and
a 2.3% prevalence of atrial fibrillation, the prevalence of atrial fibrillation in
overt hyperthyroidism was 13.8%.
In a study of more than 13,000 hyperthyroid patients, the prevalence for
atrial fibrillation was less than 2%,
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When that same group of patients was analyzed for age distribution,
prevalence increased stepwise in each decade, peaking at
approximately 15% in patients older than 70 years.
This study confirms that atrial fibrillation caused by hyperthyroidism is
more common with advancing age.
In a study of unselected patients presenting with atrial fibrillation, less
than 1% of cases was caused by overt hyperthyroidism.
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However, the ability to restore thyrotoxic patients to a euthyroid state and
sinus rhythm justifies TSH testing in most patients with recent onset of
otherwise unexplained atrial fibrillation or other supraventricular arrhythmias
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Treatment of atrial fibrillation in the setting of hyperthyroidism includes
beta-adrenergic blockade using a beta1 selective or nonselective agent
to control the ventricular response
This symptomatic measure can be accomplished rapidly, whereas
treatments leading to restoration of the euthyroid state requires more
time
Anticoagulation in patients with hyperthyroidism and atrial fibrillation is
controversial.
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The potential for systemic or cerebral embolization must be weighed
against the risk of bleeding and complications.
In a retrospective study of patients with hyperthyroidism, age rather than
atrial fibrillation was the main risk factor for embolization.
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In younger patients with hyperthyroidism and atrial fibrillation in the absence of
other heart disease, hypertension, or other independent risk factors for
embolization, the benefits of anticoagulation have not been proven and might be
outweighed by the risk.
Aspirin provides an alternative for lowering the risk for embolic events in younger
individuals and can be used safely.
Successful treatment of hyperthyroidism with radioiodine or antithyroid drugs and
restoration of normal serum levels of T4 and T3 are associated with reversion to
sinus rhythm in two thirds of patients within 2 to 3 months.
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In older patients or in the setting of atrial fibrillation of longer duration, the
rate of reversion to sinus rhythm is lower and electrical or pharmacologic
cardioversion should be attempted, but only after the patient has been
rendered euthyroid.
In a regimen that added disopyramide,300 mg/day, for 3 months after
successful cardioversion, patients were more likely to remain in sinus rhythm
than those not treated
HEART FAILURE IN THYROID DISEASE
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The cardiovascular alterations in hyperthyroidism include increased resting
cardiac output and enhanced cardiac contractility
A minority of patients presents with symptoms, including dyspnea on
exertion, orthopnea, and paroxysmal nocturnal dyspnea, as well as signs
peripheral edema, elevated jugular venous pressure, or an S3 indicative of
heart failure.
This complex of findings, coupled with a failure to increase the LV ejection
fraction with exercise, has suggests a hyperthyroid cardiomyopathy.
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Patients with long-standing hyperthyroidism and marked sinus
tachycardia or atrial fibrillation can develop low cardiac output, impaired
cardiac contractility with a low ejection fraction, an S3, and pulmonary
congestion, all consistent with congestive heart failure.
Review of such cases suggests that impairment in left ventricular function
results from prolonged high heart rate
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When the left ventricle becomes dilated, mitral regurgitation may also
develop
Recognition of this entity is important because treatment aimed at slowing
heart rate or controlling the ventricular response in atrial fibrillation appears
to improve left ventricular function, even before initiation of antithyroid
therapy
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Treatment can be started with lower doses of short-acting beta blockers
in conjunction with classic forms of treatment of acute congestiveheart
failure, including diuresis
It is important to recognize hyperthyroidism in older patients, because
they are at higher risk of cardiovascular and cerebral vascular events
TREATMENT. Treatment of patients with thyrotoxic cardiac disease
should include a beta-adrenergic antagonist to lower the heart rate to
10% or 15% above normal.
Definitive therapy can then be accomplished safely with iodine-131
alone or in combination with an antithyroid drug
HYPOTHYROIDISM
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The cardiovascular findings of hypothyroidism are more subtle.
Mild degrees of bradycardia, diastolic hypertension, narrow pulse
pressure and relatively quiet precordium, and decreased intensity of the
apical impulse are all characteristic.
The oxygen cost of work increases primarily as a result of the increase in
afterload.
Hypothyroidism produces increases in total and low-density lipoprotein
(LDL) cholesterol in proportion to the rise in serum TSH levels.
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The serum creatine kinase (CK) level is elevated by 50% to 10-fold in up to
30% of patients with hypothyroidism.
Pericardial effusions can occur consistent with the observation that patients
with hypothyroidism have an increase in the volume of distribution of albumin
and a decrease in lymphatic clearance function.
Although rare, tamponade with hemodynamic compromise can occur.
Echocardiography demonstrates small to moderate effusions in up to 30% of
overtly hypothyroid patients
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ECG in hypothyroidism is characterized by sinus bradycardia, low voltage,
and prolongation of the action potential duration and QT interval.
Increases in risk factors for atherosclerosis, including hypercholesterolemia,
hypertension, and elevated levels of homocysteine, may elevate the risk for
atherosclerosis in patients with hypothyroidism
One report has suggested increased cardiovascular morbidity and mortality
with untreated subclinical hypothyroidism.
In patients younger than 50 years of age with no history of heart disease, it is possible to initiate full replacement doses of l-thyroxine(100 to 150 μg/day)
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In patients older than 50yrs of age with known or suspected coronary artery
disease and coexistent hypothyroidism,three major issues need to be
addressed.
The first is whether coronary artery revascularization is required before
initiating thyroid hormone replacement.
If patients are not candidates for percutaneous intervention, CABG can be
accomplished in patients with unstable angina, left main coronary artery
disease, or three-vessel disease with impaired left ventricular function,
even in the setting of overt hypothyroidism.
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The second issue is in patients with known stable cardiac disease, in whom
cardiac revascularization is not clinically indicated.
Treatment of such patients should begin with low doses (12.5 μg) of l-
thyroxine and increased stepwise (12.5 to 25 μg) every 6 to 8 weeks until the
serum TSH level is normal.
Beta blockers are an ideal concomitant therapy to control heart rate
The third important issue involves patients who, potentially at risk for
coronary artery disease, exhibit no clinical signs or symptoms.
In this group, thyroid hormone replacement can be started at low doses, generally in the range of 25 to 50 μg/day, and increased by 25 μg every 6 to
8 weeks until the serum TSH level is normal.
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DIAGNOSIS: Hashimoto disease, post–radioiodine therapy for Graves
disease, and iodine deficiency are the leading causes of hypothyroidism
and produce diagnostic elevation in serum TSH levels.
The prevalence of hypothyroidism is estimated at 3% to 4% for overt
disease and 7% to 10% for the milder forms of disease, and increases
with advancing age.
TSH screening can therefore be advised for all adults,particularly patients
with hypertension, hypercholesterolemia, hypertriglyceridemia,coronary or
peripheral vascular disease, and unexplained pericardial or pleural
effusions and for various musculoskeletal syndromes or statin-associated
myopathy.
Myalgia
Non specific muscle symptoms.
Nocturnal cramping
Myopathy
Elevation of ck levels
Any associated disease
Usually with out elevation of ck
levels.
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thyroid disorders and cardiovascular disease
Hypothyroid related Statin induced
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TREATMENT: Stepwise thyroid hormone replacement using levothyroxine
sodium incrementally decreases serum TSH, serum cholesterol,and
serum creatine kinase levels and improves left ventricular performance
In the rare condition of myxedema coma, characterized by the
development of hypothermia, altered mental status,
hypotension,bradycardia, and hypoventilation in patients with severe and
long-standing hypothyroidism
The need for thyroid hormone replacement is more emergent, and
treatment can be accomplished with 100 µg of T4 or 25 to 50 µg of T3
daily, administered intravenously.
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These patients often require intensive care unit monitoring with volume
repletion, gentle warming, and ventilatory support in the face of CO2
retention.
Administration of hydrocortisone (100 mg three times daily)should be
undertaken until results of serum cortisol testing are obtained.
When treated in this manner, hemodynamics including systemic vascular
resistance, cardiac output, and heart rate improve within 24 to 48 hours
SUBCLINICAL HYPOTHYROIDISM
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It defined as a TSH level above the upper range of the reference population
(usually >5 mIU/mL), is seen in up to 9% of unselected populations, and
prevalence increases with age
Subclinical hypothyroidism alters lipid metabolism, atherosclerosis, cardiac
contractility, and systemic vascular resistance.
A large study of women in Rotterdam has shown that atherosclerosis and
myocardial infarction increase with odds ratios of 1.7 and 2.3, respectively, in
subclinical hypothyroid women.
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Restoration of serum TSH levels to normal after thyroid hormone
replacement improves lipid levels, lowers systemic vascular resistance, and
improves cardiac contractility.
Patients with subclinical hypothyroidism have prolonged isovolumic
relaxation times, whereas systolic contractile function does not change
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It is diagnosed when the serum TSH level is low (<0.1 mIU/mL) and T4 and
T3 levels are normal.
Prevalence of atrial fibrillation after 10 years was 28% in the subclinical
hyperthyroid patient population, compared with 11% in patients with normal
thyroid function, with a relative risk of 3.1.
This population-based study of more than 1000 individuals with subclinical
hyperthyroidism not receiving l-thyroxine therapy or antithyroid medication
demonstrated that a TSH level lower than 0.5 mIU/mL associated with
twofold increased mortality, with a relative risk of 2.3 to 3.3 from all causes,
which in turn was largely accounted for by increases in cardiovascular
mortality.
SUBCLINICAL HYPERTHYROIDISM
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Therapy can be individualized with regard to three specific groups.
The first group includes patients receiving thyroid hormone replacement for
hypothyroidism, in which the low TSH level is believed to be the result of
excess medication, and reduction of the dose is indicated.
The second group includes patients with a prior diagnosis of thyroid cancer
currently receiving l-thyroxine for the purpose of TSH suppression.
In younger patients, beta blockers can reverse many cardiovascular
symptoms
In older patients, the degree of TSH suppression can be relaxed by
lowering the T4 dosage.
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The third group includes patients in whom subclinical hyperthyroidism
results from endogenous thyroid gland overactivity, including Graves
disease or nodular goiter.
Younger patients in this category appear to have little or no effects.
In patients older than 60 years of age, antithyroid therapy (methimazole,
5 to 10 mg/day) can produce improvement
In patients who respond or require long-term treatment, consideration
should be given to the use of radioiodine.
AMIODARONE AND THYROID
FUNCTION
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Amiodarone is an iodine-rich antiarrhythmic agent effective for the treatment
of ventricular and atrial tachyarrhythmias.
Its 30% by weight iodine content and its structural similarity to levothyroxine
cause abnormalities in thyroid function test results in as many as 60% of
patients
Amiodarone inhibits the 5′-monodeiodination of T4 in the liver and pituitary.
Serum TSH levels initially remain normal. With more chronic treatment and
as the total body iodide content rises, T4 synthesis and release from the
thyroid gland can be inhibited, producing a rise in TSH levels.
The overall prevalence of hypothyroidism in amiodarone treated patients is
between 15% and 30%.
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Less common, but perhaps more challenging, is the development of
amiodarone-induced thyrotoxicosis.
The onset was often sudden and could occur shortly after drug initiation,
during chronic treatment, or up to 1 year after stopping therapy.
Although the pathogenesis is multifactorial, early studies distinguished
two forms of amiodarone-induced thyrotoxicosis.
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Type I occurs primarily in patients with preexisting thyroid disease and most
commonly in iodine deficient areas.
In contrast, type II disease was identified as a form of thyroiditis presumably
mediated by a variety of proinflammatory cytokines, including IL-6.
Changes in Thyroid Hormone Metabolism
That Accompany Cardiac Disease
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Following uncomplicated acute myocardial infarction, serum T3 levels
fall by about 20% and reach a nadir after approximately 96 hours.
Children and adults undergoing cardiac surgery with cardiopulmonary
bypass demonstrate a predictable fall in serum T3 levels in the
perioperative period.
Treatment strategies using acute administration of intravenous T3 to
adults after CABG have shown an improvement in cardiac output and a
fall in systemic vascular resistance.
Up to 30% of patients with heart failure have a low serum T3 level, which
occurs in patients treated with amiodarone and in those who are not. T3
replacement may provide benefit.