Thyroid

THYROID AND HEART DISEASE
DR. PRATEEK SINGH
PGY1 INTERNAL MEDICINE

 Thyroid produces 2 hormones thyroxin (t4) ; and
triidiothyronine(t3) . Acting thru thyroid hormone
receptor α and β
 These hormones play a critical role in cell differentiation
during development and help maintain thermogenic and
metabolic homeostasis in adults.

Difference between t3 and t4
 The thyroid secretes about 80mg ofT4, but only 5mg of
T3 per day.
 However,T3 has a much greater biological activity
about 10 folds thanT4.
 An additional 25mg/day ofT3 is produced by peripheral
monodeiodination of T4 by enzyme called 5’
Monodeiodenase

Source
 Thyroid hormones are unique biological molecules in thatthey
incorporate iodine in their structure.
 Thus, adequate iodine intake either through diet or water is
required for normal thyroid hormone production.
 Major sources of iodine are:
- iodized salt
- iodated bread
- dairy products
- shellfish
 Minimum requirement(RDA): 75 micrograms/day

Iodine metabolism
 Dietary iodine is absorbed in the GI tract, then taken up
by the thyroid gland (or removed from the body by the
kidneys).
 About 80% of the iodine is lost in urine where as only 20 %
is taken up by theThyroid follicular cells.
 The transport of iodide into follicular cells is dependent
upon a Na+/I-co-transportsystem.
 Iodide taken up by the thyroid gland is oxidized by
peroxide in the lumen of the follicle:
I peroxidase I+
 Oxidized iodine can then be used in production of thyroid
hormones.

Thyroglobulin
 Pituitary producesTSH, which binds to follicle cell
receptors.
 The follicle cells of the thyroid producethyroglobulin.
 Thyroglobulin is a very largeglycoprotein.
 Thyroglobulin is released into the colloid space,
where it’s tyrosine residues are iodinated by I+.
 This results in formation of monoiodotyrosine or
diiodotyrosine.

Peripheral conversion of t4-t3
 T3 has much greater biological activity thanT4.
 A large amount ofT4 (25%) is converted toT3 in
peripheral tissues.
 This conversion takes place mainly in the liver and
kidneys.
 TheT3 formed is then released to the blood stream.
 In addition toT3, an equal amount of “ReverseT3” may
also be formed.This has no biological activity.

Thyroid and heart
 The thyroid gland and heart share a close
relationship
 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

Isovolumic relaxation time, as a measure of diastolic function, is
altered across the spectrum of thyroid status. OH indicates overt
hypothyroidism; SCH, subclinical hypothyroidism; C, control; H,
hyperthyroidism; H+P, hyperthyroidism plus β-adrenergic
blockade (propranolol); and E, hyperthyroidism after treatment to
restore euthyroidism.

Thyroid function test
 The serumTSH level is the most widely used and sensitive
measure for the diagnosis of hypothyroidism and
hyperthyroidism
 SerumTSH levels increase(>5mIU/ml) in patients
with primary hypothyroidism
 SerumTSH 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

Effect of thyroid hormone on
cardiovascular system
 Increase heart rate
 Increase force of cardiac contractions Increase
stroke volume
 Increase Cardiac output
 Up-regulate catecholamine receptors

 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.

 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
cardiacovascular symptoms
 Palpitations
 Atrial Fibrillation
 Exercise Intolerance
 Systolic Hypertension
 Angina
 Peripheral Edema
 Congestive Heart Failure

 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 knownCAD, the increase in
cardiac work can produce myocardial ischemia

 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 primarilyAsian 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
 Hyperthyroidism is a well-known cause of atrial
fibrillation with a 16%–60% prevalence of atrial
fibrillation in patients with known hyperthyroidism (Ross
et al. (2016))
 Atrial fibrillation in hyperthyroid human patients is
believed to be due to a decreased atrial refractory period
and increased sympathetic tone with decreased heart-
rate variability.
 Wustmann and colleagues noted that hyperthyroid
patients with no known diagnosis of atrial fibrillation
when compared to euthyroid patients without a
diagnosis of atrial fibrillation were found to have an
increased incidence of supraventricular depolarizations
which normalized after treating the hyperthyroidism

Figure 3. Development of hyperthyroidism in patients with new-onset atrial fibrillation following hospital
discharge and in the general population from 1997–2009. Denmark
Selmer C, Hansen ML, Olesen JB, Mérie C, Lindhardsen J, et al. (2013) New-Onset Atrial Fibrillation Is a Predictor of Subsequent
Hyperthyroidism: A Nationwide Cohort Study. PLOS ONE 8(2): e57893. https://doi.org/10.1371/journal.pone.0057893
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057893

 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.

 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
event in younger individuals and can be used safely.
 Successful treatment of hyperthyroidism with radioiodine or
antithyroid drugs and restoration of normal serum levels ofT4
andT3 are associated with reversion to sinus rhythm in two
thirds of patients within 2 to 3 months.

 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 dz
 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
LVejection fraction with exercise, has suggests a hyperthyroid
cardiomyopathy.

 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

 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

 Treatment can be started with lower doses of short-acting
beta blockers in conjunction with classic forms of treatment
of acute congestive heart 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

Moyamoya disease
 Characterized by anatomic occlusion of the terminal
portions of internal carotid arteries.
 In these patients, treatment of the hyperthyroidism can
prevent further cerebral ischemic symptoms.
 This reinforces the importance of routine thyroid
function tests (to includeTSH) in patients who present
with cardiac and cerebral vascular ischemic symptoms

Hypothyroidism
 The cardiovascular findings of hypothyroidism are more subtle.
 Mild degrees of bradycardia, diastolic hypertension, narrow
pulse pressure and relatively quiet precordium, and decreased
intensity ofthe 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
serumTSH levels.

 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

 ECG in hypothyroidism is characterized by sinus bradycardia,
low voltage, and prolongation of the action potential duration
andQT 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)

 In patients older than 50yrs of age with known or suspected
coronary artery disease and coexistent
hypothyroidism,three major issues need to be addressed.
1- 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.

2- 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 serumTSH level is normal.
 Beta blockers are an ideal concomitant therapy to control
heart rate
3 - 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 serumTSH
level is normal.

 DIAGNOSIS: Hashimoto disease, post–radioiodine
therapy for Graves disease, and iodine deficiency
are the leading causes of hypothyroidism and produce
diagnostic elevation in serumTSH 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.

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 ofT4 or 25 to 50 µg ofT3 daily, administered
intravenously.

 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, hemodynamic including
systemic vascular resistance, cardiac output, and heart rate
improve within 24 to 48 hours

Sub-clinical hypothyroidism
 It defined as aTSH 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.

 Restoration of serumTSH 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

Sub-clinical hyperthyroidism
 It is diagnosed when the serumTSH level is low (<0.1 mIU/mL)
andT4 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 aTSH 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.

 Therapy can be individualized with regard to three specific
groups.
1- The first group includes patients receiving thyroid hormone
replacement for hypothyroidism, in which the lowTSH level is
believed to be the result of excess medication, and reduction
of the dose is indicated.
2- 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 ofTSH suppression can
be relaxed by lowering theT4 dosage.

3- The third group includes patients in whom subclinical
hyperthyroidism results from endogenous thyroid
gland overactivity, includingGraves 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.

 Antiarrhythmic drug with a high iodine content (75mg iodine/200mg)
 Can cause either hypothyroidism (5% to 25% of treated patients) or
hyperthyroidism (2% to 10% of treated patients)
 Inhibits of 5´-deiodinase activity → Inhibits conversion of T4 to T3
 Iodine released from amiodarone metabolism directly inhibit thyroid
gland function, if the effect persists, lead to amiodarone-induced
hypothyroidism
 Preexistent thyroid disease and Hashimoto’s thyroiditis ↑ risk
 If hypothyroidism develop with a persistent rise in TSH: L-thyroxine
therapy started
Amiodarone & thyroid function





Type 1 hyperthyroidism:
• iodine-induced excess thyroid hormone synthesis
• underlying thyroid disorder, e.g., nodular goiter or latent GD
• in regions where iodine intake is low
Type 2 hyperthyroidism:
• thyroiditis due to a direct cytotoxic effect of amiodarone →↑release of
thyroid hormones → transient thyrotoxicosis in a previously normal
thyroid gland
Can overlap & difficult to distinguish, RIU is low in both types
Point favors Type 2 hyperthyroidism: Signs of inflammation, elevated ESR
& IL-6, modest increases in thyroid gland size

 ATDs effective in type 1, ineffective in type 2 thyrotoxicosis.
 Prednisolone is beneficial in the type 2 form
 Beta blocker should be started
 A pragmatic approach is to commence combination
therapy with an ATD and glucocorticoid in patients with
significant thyrotoxicosis
 A rapid response (within 1–2 weeks) usually indicates a type
2 picture and permits withdrawal of the antithyroid therapy
 A slower response suggests a type 1 picture, when
antithyroid drugs may be continued and prednisolone
withdrawn.
 Potassium perchlorate can be used to inhibit iodine trapping
in thyroid

 If the cardiac state allows, amiodarone should be
discontinued
 The course of the disease may last for anywhere
between 1 to 3 months
 In rare cases, surgical thyroidectomy under local
anesthesia has proven to be effective
 To minimize the risk of type 1 thyrotoxicosis, thyroid
function should be measured in all patients prior to
commencement of amiodarone therapy, and amiodarone
should be avoided if TSH is suppressed
 In general, patients treated with amiodarone should
have thyroid function (specificallyTSH) testing
periodically throughout therapy

Take home message
 Thyroid dysfunction (both hypo & hyper) virtually affects
the whole spectrum of cardiovascular hemodynamics
 Thyroid functional abnormality can case a range
of cardiovascular signs-symptoms and
cardiovascular diseases are also associated with
derangement of thyroid functions
 Restoration of normal thyroid function most often
reverses the abnormal cardiovascular hemodynamics

thankyou
 In 1786, Caleb Hillier Parry
described a woman with
goiter and palpitations, whose
"each systole shook the
whole thorax".
 He was the first to suggest
"the notion of some
connexion (sic) between the
malady of the heart and the
bronchocoele" (Parry CH,
1815, Crutwell, Bath).

Thyroid

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