Transcript Thyroid and heart diseases

Thyroid and heart diseases
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A relation between the thyroid and the heart has long been
recognized .
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In the late 1700s, a patient with clinical features of
thyrotoxicosis including palpitations, irregular pulse, and
dyspnea was described .
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In the early 1900s, a patient with “myxedema heart” was
reported: The critical findings were enlarged cardiac
silhouette, low electrocardiographic voltage, and
bradycardia .
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Thyroxine (T4), is the major secretory product of the
thyroid gland. Triiodothyronine (T3), the biologically active
compound, is in large part derived from peripheral
conversion of T4 by the 5'-monodeiodinase enzyme.
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Cardiovascular manifestations are frequent in thyroid
dysfunction and may be the result of
direct hormone effects at the cellular level,
interactions with the sympathetic nervous system, or
alterations of peripheral circulation and metabolism .
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At the cellular level, thyroid hormones act mainly through
binding to specific nuclear receptors and activation of gene
transcription . Additionally, they activate extranuclear sites
as mitochondrial and membrane-bound enzymes .
Hyperthyroidism
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Hyperthyroidism is the clinical state resulting from excess
production of T4 , T3 or both.
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The most common cause is a diffuse toxic goiter (Graves
disease). Although the etiology of this condition is still
unknown, the hyperproduction of T4 and T3 is thought to
result from circulating IgG autoantibodies that bind to the
thyrotropin receptor on the thyroid gland.
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The second most common form of hyperthyroidism is
nodular toxic goiter, a condition in which localized areas of
the gland function excessively and autonomously.
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Hyperthyroidism is a relatively common disease that
occurs four to eight times more often in women than men,
with a peak incidence in the third and fourth decades.
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signs and symptoms include
fatigue, hyperactivity, insomnia, heat intolerance,
palpitations, dyspnea, increased appetite with weight loss,
nocturia, diarrhea, oligomenorrhea, muscle weakness,
tremor, emotional lability, increased heart rate, systolic
hypertension, hyperthermia, warm moist skin, lid lag, stare,
and brisk reflexes. Serum T4 levels are increased and
serum TSH is suppressed
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CARDIOVASCULAR MANIFESTATIONS.
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Palpitations, dyspnea, tachycardia, and systolic
hypertension are common findings. Diastolic hypertension
can also occur.
Typically noted are a hyperactive precordium with
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a loud first heart sound,
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an accentuated pulmonic component of the second heart
sound, and
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a third heart sound; .
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It has been suggested that many of the changes in cardiac
function are secondary to the increased metabolic demands
of peripheral tissue.
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also thyroid hormone exerts a direct cardiac stimulant
action independent of its effect on general tissue
metabolism,.as, normalization of the myocardial contractile
response to exercise may not occur until several months
after normalization of thyroid function .
Roentgenographic and electrographic changes,
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are nonspecific in hyperthyroidism. Thus, on chest x-ray
the left ventricle, aorta, and pulmonary artery are
prominent, and in some cases, generalized cardiac
enlargement can be noted.
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In patients with sinus rhythm, the magnitude of the
tachycardia in general parallels the severity of the disease.
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Sinus tachycardia is present in 40 percent of patients with
hyperthyroidism and occurs most frequently in the younger
age groups and often at night
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ten to 15 percent of patients with hyperthyroidism have
persistent atrial fibrillation, which is often heralded by one
or more transient episodes of this arrhythmia
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Intraatrial conduction disturbances, manifested by
prolongation or notching of the P wave and , occur in 15
and 5 percent of patients with hyperthyroidism,
respectively.
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Occasionally, second- or third-degree heart block may
result. The cause of the AV conduction disturbance is not
clear
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Intraventricular conduction disturbances, most commonly
right bundle branch block, occur in about 15 percent of
patients with hyperthyroidism without associated heart
disease of other etiology
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Paroxysmal supraventricular tachycardia and flutter are rare
in hyperthyroidism.
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Finally, occult thyrotoxicosis may underlie either chronic
or paroxysmal isolated atrial fibrillation
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In most instances the development of clinical
manifestations of heart failure and myocardial ischemia in
patients with hyperthyroidism signifies the presence of
underlying cardiac or coronary vascular disease.
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Both angina pectoris and heart failure occur in patients
with hyperthyroidism.
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For many years it was assumed that these conditions were
seen only in the presence of underlying cardiovascular
disease.
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More recently, however, lines of evidence have suggested
otherwise:
(1) Congestive heart failure has been produced in
experimental animals by simply administering T4 .
(2) Congestive heart failure may develop in children with
thyrotoxicosis and no underlying cardiac disease.
(3) Angina has been reported in a hyperthyroid patient with
normal coronary arteries, presumably secondary to thyroidinduced coronary artery spasm.
(4) The abnormal left ventricular function observed during
exercise in hyperthyroid subjects is not reversed by beta
blockade but is reversed by treating the hyperthyroidism.
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The frequency of hyperthyroidism is also increased in
patients with familial hypertrophic cardiomyopathy.
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Finally, hyperthyroidism is associated with mitral value
prolapse in more than a third of cases.
DIAGNOSIS AND TREATMENT OF
HYPERTHYROIDISM
 The diagnosis is confirmed with a low TSH level, which
reflects an elevated level of thyroid hormone in the blood.
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In elderly patients with hyperthyroidism, cardiovascular
manifestations predominate, specifically, atrial fibrillation
and/or congestive heart failure, and therefore evaluation of
thyroid function in such patients is particularly important.
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Definitive treatment of hyperthyroidism is surgical removal
of the gland or irradiation with radioactive iodide.
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In severely ill patients, particularly those with thyroid
storm, significant cardiovascular symptoms, or both,
neither of these therapies is appropriate .
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Thus, medical therapy is directed at reducing both the
production and the biological effect of thyroid hormone
with thionamides and beta blockers.
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Tachycardia, palpitations, tremor, restlessness, muscle
weakness, and heat intolerance are reversed by these
agents, which offer the additional benefit of inhibiting the
conversion of T4 to the biologically active T3 in peripheral
tissues.
TREATMENT OF CARDIOVASCULAR
MANIFESTATIONS OF HYPERTHYROIDISM.
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Prompt treatment of hyperthyroidism can significantly
reduce, if not eliminate the associated cardiovascular
symptoms.
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About half of patients with concurrent onset of
hyperthyroidism and angina pectoris experience complete
remission of this symptom after treatment of
hyperthyroidism
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Furthermore, in 30 to 40 percent of thyrotoxic patients
with atrial fibrillation sustained for 1 week or longer,
spontaneous reversion to sinus rhythm occurs when they
become euthyroid.
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Beta-blocking drugs also control the ventricular rate in
atrial fibrillation.
The most useful agents for correcting the fundamental
defect are thionamides such as propylthiouracil, which
inhibits thyroid hormone synthesis.
Iodine inhibits the release of thyroid hormones from the
thyrotoxic gland, and its beneficial effects occur more
rapidly than those of thionamides. It is therefore useful for
rapid amelioration of the hyperthyroid state in patients
with thyroid heart disease
The nonselective agent propranolol has been traditionally
used , but selective beta1-adrenergic antagonists such as
atenolol appear equally effective.
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If beta-blockers are contraindicated, calcium channel
blockers such as verapamil or diltiazem can be
administered as negative chronotropic agent. However,
caution is warranted, as these agents may lead to
hemodynamic instability by further reducing systemic
vascular resistance and contractility.
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Hyperthyroid patients with cardiovascular disease are
particularly resistant to therapy. It has been well
documented that both heart failure and arrhythmias are
resistant to conventional doses of cardiac glycosides.,
serum levels of cardiac glycosides are diminished in
hyperthyroidism, because its metabolism is increased ,
toxicity may develop at a dose that has relatively little
therapeutic effect.
Hypothyroidism
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Hypothyroidism is the clinical syndrome associated with
decreased secretion of thyroid hormones. This condition
reflects in over 90% of cases a disease of the gland itself
(primary hypothyroidism). Rarely, hypothyroidism can be
caused by pituitary disease (secondary hypothyroidism) or
hypothalamic disease (tertiary hypothyroidism).
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The most frequent cause of hypothyroidism in adults is
autoimmune thyroiditis, or Hashimoto’s disease.
Accordingly, women are more frequently affected.
 clinical manifestations ,
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dry skin, weight gain, fatigue, and forgetfulness, Other
complaints of hypothyroid patients include increased
tiredness and sleep requirement, depressed mood, cold
intolerance, constipation, and decreased exercise tolerance.
Pleural effusions and pitting edema may occur in absence
of heart failure.
Cardiovascular Involvement
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Bradycardia is common, and
pericardial effusion may occur in up to one-half of patients
but rarely causes hemodynamic compromise .
Both diastolic and systolic LV performance may be
decreased , presumably because of alterations in calcium
uptake and release by cardiac myocytes . Additionally,
an increase in systemic vascular resistance is observed,
possibly as the result of the lack of direct vasodilatory
effect of thyroid hormones .
The resulting hemodynamic changes are opposite but less
marked than with thyrotoxicosis. Characteristic features
include low cardiac output; decreased stroke volume,
diastolic function, and increased systemic vascular
resistance .
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As in patients with thyrotoxicosis, overt heart failure in
hypothyroidism generally represents exacerbation of
intrinsic cardiac disease. Rarely, however, hypothyroidism
alone may cause cardiomyopathy . Therefore, unexplained
heart failure should prompt determination of thyroid
hormones.
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In the absence of underlying heart disease, the decreased
myocardial contractility observed in hypothyroidism is
generally reversible after hormone replacement , probably
as a result of improved calcium handling in cardiac
myocytes and decreased systemic vascular resistance .
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Total cholesterol, low-density lipoprotein (LDL)
cholesterol, very-low-density lipoprotein (VLDL)
cholesterol, lipoprotein(a), and apolipoprotein B
concentrations are often elevated in hypothyroidism; some
patients have high serum triglyceride levels .
It has been demonstrated that patients with
hypothyroidism have an intrinsic LDL catabolism
dysfunction, which is reversible after hormone replacement
. Therefore, screening for this condition is mandatory when
assessing patients with hyperlipidemia.
The powerful interaction between thyroid hormones and
lipid metabolism is highlighted by the fact that thyroid
hormones have been used in the past as lipid-lowering
agents. However, this strategy was associated with
increased morbidity and mortality in patients after
myocardial infarction .
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Patients with hypothyroidism frequently have risk factors
for coronary artery disease, but data to support the direct
association between hypothyroidism and coronary artery
disease are lacking .
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The suggestion that hypothyroidism may indeed represent
an independent risk factor for coronary disease comes from
a population-based cross-sectional study.
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Hypothyroidism is associated with increased prevalence of
hypertension. In a review of 12 studies, the overall
prevalence of hypertension was 21% . In large series of
hypertensive patients, hypothyroidism accounted for 3% to
5% of the cases .
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Hypothyroid patients have a low-renin form of
hypertension, and the mechanism remains unknown . The
causal link between thyroid hormone deficiency and
hypertension is confirmed by the fact that hormone
replacement may lead to improvement of hypertension .
Diagnosis and Therapy
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An elevated TSH combined with a low free T4 is diagnostic
of primary hypothyroidism. Antimicrosomal and
antithyroglobulin antibodies are characteristic of
Hashimoto’s disease.
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Hypothyroidism is preferentially treated with thyroxine
because of its long half-life
Amiodarone and Thyroid Dysfunction
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Amiodarone is an iodine-rich benzofuran derivative with
similar molecular structure to thyroid hormones. Organic
iodine represents almost 40% of the molecular weight of
amiodarone. A daily dose of 200 mg of amiodarone
corresponds to an intake of 75 mg of organic iodide and
generates approximately 7 mg of free iodine .
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Given the fact that the normal dietary requirement of
iodine is 100 to 200 µg per day, amiodarone therapy is
associated with an enormous iodide load, reflected in a 40fold increase in plasma and urinary iodide levels .
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it is not surprising that over 50% of the patients on
amiodarone have abnormal thyroid function test results,
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The predominant peripheral action of amiodarone on
thyroid hormones is the inhibition of the deiodination of
T4 to T3. As a result, the serum levels of T4 increase and
the levels of T3 decrease
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In addition, high iodide availability initially inhibits
thyroid hormone synthesis.
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During the first 3 months of therapy, TSH levels are
commonly slightly elevated because of lack of feedback
inhibition, due to the lowered T3 levels, but they tend to
normalize during long-term administration.
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Amiodarone-induced thyrotoxicosis (AIT) prevails in areas
with low iodine intake, and hypothyroidism is more
frequent in areas with high iodine intake.
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Whereas thyrotoxicosis can occur throughout the treatment
period and even several months after treatment,
hypothyroidism rarely develops beyond 18 months of
initiation of therapy.
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Monitoring of thyroid function in this setting relies on
TSH. If TSH is abnormal, free T4 and free T3 levels should
be assessed. Additional assessments are recommended at
approximately 3 months and yearly thereafter.
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A noniodinated analog of amiodarone, dronedarone, has
been synthesized. Preliminary animal data show that this
compound has similar electrophysiologic effects to
amiodarone .
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The development of dronedarone or a similar compound
will be followed with interest, because iodine deletion is
expected to overcome endocrine side effects of
amiodarone. However, extensive safety and efficacy data in
animals are required before human testing.
Amiodarone-Induced Hypothyroidism
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incidence ranging from 13% in iodine-replete countries to
6% in countries with low or intermediate iodine intake
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TSH levels above 10 to 15 mU per L in patients on chronic
amiodarone usually represent hypothyroidism. The
diagnosis is confirmed by low T4 or free T4. The
assessment of T3 or free T3 adds little information
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Once the diagnosis of hypothyroidism is established, the
drug can be safely continued, if needed, and thyroxine
replacement added in increasing doses at 4- to 6-week
intervals until TSH returns within normal limits and
symptoms resolve .
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If amiodarone is discontinued, recovery of thyroid function
is influenced by the presence of thyroid antibodies. In fact,
the absence of antibodies is associated with frequent
recovery, mostly within a few months, whereas patients
with thyroid antibodies usually do not recover normal
thyroid function .
Amiodarone-Induced Thyrotoxicosis
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In countries with high iodine intake, AIT is less frequent
than hypothyroidism, with an estimated incidence of
approximately 2%. In contrast, in the presence of iodine
deficiency, AIT may occur in up to 10% .
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Antiadrenergic effects of amiodarone may partially
conceal thyrotoxic symptoms. AIT should be suspected in
the presence of new or recurrent atrial arrhythmias or
unexplained weight loss.
Three pathophysiologic mechanisms associated with
thyrotoxicosis in the setting of chronic amiodarone therapy
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First, iodine may affect thyroid autoregulatory mechanisms
and may lead, particularly in patients with underlying
thyroid disease, to excessive hormone synthesis.
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Second, inflammatory destructive histologic changes and
increased cytokines (e.g., interleukin-6) and thyroglobulin
levels have been demonstrated in this setting, suggesting a
direct cytotoxic effect of amiodarone .
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Third, it has been postulated that amiodarone may trigger
an autoimmune response to the thyroid gland.
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Amiodarone should be discontinued whenever possible.
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The choice of treatment can be guided by distinction of
two forms of AIT.
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In type I AIT patients have a goiter, positive thyroid
antibodies, and abnormal (i.e., measurable or even high)
24-hour radioiodine uptake. Treatment consists of a
combination of thionamides, propylthiouracil , which
inhibit hormone biosynthesis, and potassium perchlorate,
which blocks thyroid iodide uptake .
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type II AIT have a normal thyroid and low radioiodine
uptake. The efficacy of corticosteroids, alone or in
combination with thionamides, has been convincingly
demonstrated in this settin.
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However, because a mixed form of AIT is frequent,
patients can be approached pragmatically with an initial
combination of thionamides and potassium perchlorate,
with corticosteroids being added after 2 weeks if no
improvement occurs . In patients not responding to this
therapy, lithium may be a valid alternative .
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