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.