Discussion
Thyroid
hormones have significant effects on cardiovascular system through
genomic nuclear and extranuclear nongenomic mechanisms,which have been
well worked out. Both of them act together to regulate cardiac function
and cardiovascular
hemodynamics4。Excess
thyroid hormone acting on the heart and peripheral vasculature include
decreased systemic vascular resistance (SVR) and increased resting heart
rate, left ventricular contractility,
and blood volume5. The decreased
systemic
vascular resistance leads to reduction in renal perfusion pressure,
activation of the renin-angiotensin-aldosterone system (RAAS), thereby
promotes sodium retention and blood
volume in the body6.
These
Hemodynamic variations combine to
promote an increase in blood volume and preload, which increase cardiac
output 50% to 300% higher than in normal individuals7
8 9. Excess amounts of thyroid hormone have a significant impact on
cardiovascular hemodynamics have been observed in our patient, including
tachycardia, widened pulse pressure,atrial fibrillation,cardiomegaly,
congestive heart failure.
Tachycardia is the most common
rhythm disturbance and recorded in almost all patients with
hyperthyroidism10, Atrial fibrillation occurs in 10 to 25 percent of
patients with hyperthyroidism11 12. An investigation
in Japan revealed that tachycardia ≥150 bpm was associated with
increased mortality in thyroid storm patients13,The
presence of AF in patients with hyperthyroidism is associated with
significant mortality14. Increased left ventricular
mass caused by elevated left atrial pressure,impaired ventricular
relaxation, ischemia resulting from raised resting heart rate and
increased atrial ectopic activity15,these underlying
factors relates to atrial fibrillation accelerate systemic hemodynamic
deterioration.
More evidence suggest
cardiovascular complications account for most of the deaths in
hyperthyroid patient8. Therefore cardiac
manifestations in the setting of thyrotoxicosis should be treated
promptly and aggressively. Beta-blockers are selected as first-line
treatment for ventricular rate control of Graves’ hyperthyroidism. They
not only to help ameliorate symptoms such as palpitations and tremor,
especially in the stage before ATD
take effect. but also to decrease the ventricular response to AF by
action on the β1 receptors,. Betablockers (such as landiolol, esmolol
and bisoprolol) with higher selectivity in cardiovascular system have
higher cardioprotective effects and superior prevention of atrial
fibrillation, especially for patients with
bronchospasm16.
Hyperthyroidism may complicate, if left untreated tachycardia and AF
last for a long period of time,hemodynamic changes predispose the
patient to heart failure. the concept of “tachycardia-induced
cardiomyopathy” related to hyperthyroidism is more plausible, as HF
commonly improves with adequate control of the heart rate and AF when
the euthyroid state is restored. Some reported cases of congestive heart
failure with Graves’ hyperthyroidism had increased pulmonary resistance,
autoimmune mechanisms with subsequent endothelial damage may have an
important role in its occurrence17 18. Our patient had
features of high-output congestive heart failure with pulmonary
hypertension, as evidenced by raised jugular venous pressure neck veins
engorged and bilateral pedal edema, Echocardiogram reported RVDd is
increased significantly in our patients,but SV and CO of left ventricle
almost normal(Figure 2),which means Graves’ hyperthyroidism causes
increased cardiac output and a hyperdynamic right ventricle, right
ventricular function decreases more significantly than the left
ventricular function. The deteriorating of congestive heart failure due
to hyperthyroidism in our patient means it is not limited to the
elderly, but can develop even in young patients.
Brain natriuretic peptide (BNP) is mainly synthesized and secreted by
myocytes in the left ventricle (LV) as a response to myocytes stretched
by pressure overload or volume expansion of the
ventricle,Although
BNP is steadily increased in HF, it may often be insufficient to reduce
the sodium retention and vascular constriction due to activation of
RAAS19.
Therefore,
use of diuretics is fundamental in the
treatment of signs of fluid
overload and congestion in patients
with HF in hyperthyroidism. Initial treatment with furosemide in our
patient is ineffective,
torasemide
was admitted intravenously, as the clinical trial has suggested patients
treated with torasemide fluid overload and symptoms improved more than
in the furosemide group. Meanwhile, using the
aldosterone
receptor antagonist
spironolactone
to block RAS system, which acts
primarily by competitive binding to the aldosterone-dependent
sodium-potassium exchange sites located in the DCT and collecting duct.
The effect of the blockade is to decrease sodium reabsorption with water
retention and to increased potassium retention.
Compare with the increased cardiac
output and peripheral circulation, the hepatic blood
flow is little increased
in
the early stage of Graves’
hyperthyroidism. Under this condition, the growth of splanchnic oxygen
consumption in hyperthyroidism is accomplished by an increased oxygen
extraction. This could result in anoxia of the centro-lobular zones of
the liver and may well be related to the centro-lobular
necrosis20. It may lead to mild elevations in
transaminases, which occur in up to 50% of patients with untreated
hyperthyroidism. thyrotoxicosis might also have a direct toxic effect on
hepatic tissue. This may interfere with bile transport resulting in
cholestasis with hyperthyroidism. In a rat model of thyrotoxicosis,
plasmatic and intracellular
organoid membranes of hepatocytes
in ultrastructure were significant damaged, which has an adverse effect
on the functionality of the liver21.
The right heart failure in
long-standing hyperthyroidism can cause passive liver congestion Liver
dysfunction may range from mild hyperbilirubinemia, coagulopathy, and
hepatomegaly to ascites and liver cirrhosis. Decreased cardiac output
may be associated with acute hepatocellular necrosis with marked
elevations in serum aminotransferases22.
Therefore, the guidelines for the
management of thyroid storm recommends that
treatment
of congestive heart failure could
contribute to the recovery of normal liver function. which is one of the
most common causes of hepatic damage and jaundice13.
we suspected the pre-existing chronic
liver disease in this patient until the current episode, mainly because
she had taken herbal remedies for two years, cases of herb-induced liver
injury have been highlighted in many publications. Hyperthyroidism also
reasonably consist of chronic liver injury as result of a long period of
noncontrolled hyperthyroidism due to
her poorly ATD compliance and the paucity of liver function tests.
Graves’ hyperthyroidism patients
should be rendered euthyroid before
RAI
therapy. Considering possibility of
oral ATD-induced hepatotoxicity, methimazole cream has been admitted to
our patient for correcting hyperthyroidism, Thyroxine concentration
decreased and normalized after 20 days treatment of methimazole cream.
we also adopted therapeutic plasma exchange (TPE) to remove harmful
substances, circulating thyroid hormone and bilirubin and to replace
coagulation factor and plasma factor, which is a useful adjunct as a
bridge to the remedy when
hyperbilirubinemia cannot be
controlled effectively.
In summary, as observed in our clinical practice and described in the
literature, tachycardia and AF,
early manifestations of hyperthyroidism indicate significant hemodynamic
alterations in cardiovascular system, Untreated high-output state and
hyperthyroidism can lead to ventricular dilation and persistent
tachycardia, further deterioration in hemodynamic can result in chronic
heart failure and liver dysfunction even a fatal event.
The continuum of disease present
the pathophysiology development of Graves’ hyperthyroidism,Therefore,
we have got some conception that
hemodynamic variation is a dominant contributing factor of Graves’
hyperthyroidism complication, the prompt identification and effective
therapeutics of cardiac manifestations in hyperthyroidism patients is
compulsory because the prognosis of it may be improved with the
appropriate treatment.