Pericardial effusion associated with subclinical hypothyroidism

Previous studies have suggested that subclinical thyroid dysfunction, as manifested by abnormalities in thyroid-stimulating hormone (TSH) levels, are associated with detrimental effects on the cardiovascular system. Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Subclinical hypothyroidism is defined by elevated serum levels of TSH with normal levels of free thyroid hormones. Subclinical hypothyroidism is characterized by abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated risk of atherosclerosis, and ischemic heart disease. It has been reported that sub-clinical hypothyroidism is associated with both, a significant risk of coronary heart disease at baseline and at follow-up and that mortality from cardiovascular causes is significantly higher at follow-up. However subclinical thyroid dysfunction is currently the subject of numerous studies and remains controversial, particularly as it relates to cardiovascular morbidity and mortality and clinical applications. Pericardial effusion can be present in systemic disorders including hypothyroidism. We present a case of subclinical hypothyroidism in a 41-year-old Italian woman with an ubiquitary pericardial effusion. Also this case focuses attention on subclinical hypothyroidism.     

老年人甲状腺功能异常与心血管疾病

甲状腺功能异常与心血管疾病密切相关。老年人促甲状腺激素分布曲线向高水平方向偏移,因此,需应用年龄特异的参考范围判断甲状腺功能状态。近来,亚临床甲状腺疾病日益得到重视。研究表明亚临床甲状腺功能亢进（亚甲亢）可引起心脏结构和功能的改变,可引起房颤的发生率增加。而亚临床甲状腺功能减退（亚甲减）可能是心力衰竭、缺血性心脏病、全因死亡的一个潜在危险。异常甲状腺功能经纠正后,与甲亢和甲减相关的心血管疾病可得到缓解。基于老老年患者中亚临床甲减可能有保护作用,因此,亚临床甲状腺功能异常对心血管疾病的影响以及何种患者经过治疗可以获益,需要更多的循证医学的证据用以指导临床实践。     

Cardiovascular risk with subclinical hyperthyroidism and hypothyroidism: pathophysiology and management

Previous studies have suggested that subclinical thyroid dysfunction, as manifested by abnormalities in thyroid-stimulating hormone (TSH) levels, are associated with detrimental effects on the cardiovascular system. Subclinical hypothyroidism is characterized by abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated risk of atherosclerosis, and ischemic heart disease. Similarly, patients with subclinical hyperthyroidism have nearly 3 times the likelihood of atrial fibrillation over a 10-year follow-up interval, raising the question of whether patients with subclinical hyperthyroidism should be treated to prevent atrial fibrillation. A single measurement of low serum TSH in individuals aged 60 years or older has been reported to be associated with increased mortality from all causes and in particular from circulatory and cardiovascular disease in a 10-year follow-up study. Subclinical thyroid dysfunction is currently the subject of numerous studies and remains controversial, particularly as it relates to cardiovascular morbidity and mortality and clinical applications.     

Cardiovascular morbidity and mortality in thyroid dysfunction

This review summarizes present knowledge from clinical and epidemiological studies with respect to cardiovascular complications in thyroid disorders, focusing on cardiovascular morbidity and mortality. Consistently, good evidence exists for an increased cardiovascular morbidity in overt hyperthyroidism, and an association with predictors of cardiovascular mortality like ventricular hypertrophy, ventricular dysfunction, and atrial fibrillation. As for subclinical hyperthyroidism evidence is conclusive only with respect to an up to 5.2-fold elevated risk for atrial fibrillation. The cardiovascular risk profile of overt hypothyroidism is characterized mainly by risk factors of atherosclerosis such as hypercholesterolemia and hypertension, but also by possible development of heart failure. In contrast, data on such parameters are inconsistent for subclinical hypothyroidism. Although many of these cardiovascular alterations may hypothetically worsen prognosis, results from cohort and retrospective studies do not consistently point towards increased mortality. Only for overt hyperthyroidism an up to 1.7 fold elevated risk for cardiovascular diseases and up to 1.7 fold increased cardiovascular mortality rates have been demonstrated. However, the evidence for similarly increased cardiovascular morbidity and mortality rates in subclinical hyperthyroidism and hypothyroidism is inconclusive, and the evidence is non-existent for overt hypothyroidism. Further randomized clinical studies and population-based cohort-studies are required and should consider major cardiovascular risk factors and adverse cardiovascular events and mortality.     

Thyroid disease and the heart

The cardiovascular signs and symptoms of thyroid disease are some of the most profound and clinically relevant findings that accompany both hyperthyroidism and hypothyroidism. On the basis of the understanding of the cellular mechanisms of thyroid hormone action on the heart and cardiovascular system, it is possible to explain the changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances that result from thyroid dysfunction. The importance of the recognition of the effects of thyroid disease on the heart also derives from the observation that restoration of normal thyroid function most often reverses the abnormal cardiovascular hemodynamics. In the present review, we discuss the appropriate thyroid function tests to establish a suspected diagnosis as well as the treatment modalities necessary to restore patients to a euthyroid state. We also review the alterations in thyroid hormone metabolism that accompany chronic congestive heart failure and the approach to the management of patients with amiodarone-induced alterations in thyroid function tests.     

Subclinical hypothyroidism and cardiac function.

The cardiovascular system is sensitive to the action of thyroid hormone. However, although a wide spectrum of cardiac abnormalities has long been recognized in patients with overt thyroid dysfunction, the question of cardiac involvement in patients with subclinical thyroid dysfunction has been investigated only in the last two to three decades. Most clinical studies have shown that subclinical hypothyroidism or hyperthyroidism is associated with changes in several cardiac parameters. More specifically, the literature on cardiac involvement in subclinical hypothyroidism consistently shows that patients have resting left ventricular diastolic dysfunction evidenced by delayed relaxation, and impaired systolic dysfunction on effort that results in poor exercise capacity. Whether or not subclinical hypothyroidism also affects left ventricular systolic function at rest remains controversial. Studies of subclinical hypothyroid patients before and after euthyroidism was achieved with levothyroxine replacement provided evidence of impaired resting left ventricular systolic function. Indeed, at-rest left ventricular systolic function was substantially normal in most studies of subclinical hypothyroid patients compared to normal control subjects. Drawing on these data, it appears that subclinical hypothyroidism should be considered a mild form of thyroid failure, associated with initial signs of cardiovascular hypothyroidism. Therefore, it would seem appropriate to initiate timely treatment of patients with mild thyroid failure to prevent cardiac involvement.     

亚临床甲状腺功能异常与心血管疾病的关系

临床研究显示,亚临床甲状腺功能异常与心血管疾病之间存在密切的关系.亚临床甲状腺功能减退通常伴有血脂异常、高凝状态、纤维蛋白溶解活性减低等心血管疾病危险因素,其与动脉粥样硬化、冠心病和心血管死亡的风险显著相关.另一方面,亚临床甲状腺功能亢进与心房颤动发生风险显著相关,但与心血管死亡风险的相关性尚不清楚.对于亚临床甲状腺功能异常进行治疗是否能够带来心血管获益,目前尚无确切结论.     

亚临床甲状腺功能异常与心血管疾病的关系

临床研究显示,亚临床甲状腺功能异常与心血管疾病之间存在密切的关系.亚临床甲状腺功能减退通常伴有血脂异常、高凝状态、纤维蛋白溶解活性减低等心血管疾病危险因素,其与动脉粥样硬化、冠心病和心血管死亡的风险显著相关.另一方面,亚临床甲状腺功能亢进与心房颤动发生风险显著相关,但与心血管死亡风险的相关性尚不清楚.对于亚临床甲状腺功能异常进行治疗是否能够带来心血管获益,目前尚无确切结论.     

亚临床甲状腺功能异常与心血管疾病的关系

临床研究显示,亚临床甲状腺功能异常与心血管疾病之间存在密切的关系.亚临床甲状腺功能减退通常伴有血脂异常、高凝状态、纤维蛋白溶解活性减低等心血管疾病危险因素,其与动脉粥样硬化、冠心病和心血管死亡的风险显著相关.另一方面,亚临床甲状腺功能亢进与心房颤动发生风险显著相关,但与心血管死亡风险的相关性尚不清楚.对于亚临床甲状腺功能异常进行治疗是否能够带来心血管获益,目前尚无确切结论.     

Thyroid hormone and heart failure

Thyroid hormone metabolic disarray has been identified as a risk factor for the progression of heart disease and the development of heart failure (HF). Both hyper-and hypothyroidism have been associated with a failing myocardium. Poor cardiac contractility and low cardiac output due to hyperthyroidism is a rare occurrence and is mostly seen in patients with preexisting heart disease. Referred to as a "rate related" phenomenon, hyperthyroid-induced sustained sinus tachycardia or atrial fibrillation may further reduce ventricular contractility. Increasingly, the hypothyroid state, and in particular a low triiodothyronine level, has been associated with a reduced cardiac performance and poor prognosis in HF, even in the presence of normal thyroid-stimulating hormone levels. Low thyroid hormone levels alter cardiac gene expression and increase systemic vascular resistance, both resulting in a reduction of cardiac contractility and cardiac output. This review summarizes current data on thyroid dysfunction and HF as well as the emerging implications of the "low triiodothyronine state."     

甲状腺疾病与心脏

甲状腺激素水平异常可导致心脏发生相应的病变。临床上常见的甲状腺疾病如甲状腺功能亢进和甲状腺功能减退,除引起常见的心房颤动外,还影响心脏收缩功能、血流动力学、心力衰竭发展以及血脂等。甲状腺功能异常导致的心脏疾病常有一定的可逆性。所以,临床上了解甲状腺功能对心脏疾病的诊疗都有很大的帮助。     

Thyrotoxicosis and the cardiovascular system

Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. Palpitations, caused by sinus tachycardia and occasionally by atrial fibrillation, are the most frequent cardiovascular symptom. As atrial fibrillation may be the only manifestation of thyrotoxicosis, thyroid hormone excess should routinely be excluded in patients with this rhythm disturbance. Heart failure occurs mostly in the presence of underlying heart disease or tachycardia-induced cardiomyopathy in patients with long-standing atrial fibrillation. On occasion, long-standing hyperthyroidism may lead to heart failure even in the absence of concomitant cardiac conditions. Beta-blockers offer symptomatic relief and at the same time slow the ventricular response in patients with atrial fibrillation. Amiodarone, and occasionally iodinated contrast agents, may cause iodine-induced thyrotoxicosis. Clinical suspicion is essential in the diagnosis of amiodarone-induced thyrotoxicosis (AIT), because the antiadrenergic effect of the drug may conceal symptoms. AIT should be considered in any patient on amiodarone in the presence of new-onset or recurrent atrial arrhythmias or unexplained weight loss. Beyond discontinuation of amiodarone, treatment options include propylthiouracil or methimazole, potassium perchlorate, steroids, lithium and, if pharmacological treatment fails, surgery. Amiodarone may potentially be used less frequently in the future since recent studies have shown that this drug is inferior to implantable cardioverter defibrillators in prevention of sudden cardiac death in patients with severe heart failure. In addition, non-iodinated amiodarone analogues are currently in advanced phase of clinical testing.     

Subclinical thyroid dysfunction and cardiovascular consequences: An alarming wake-up call?

Subclinical thyroid dysfunction (STD), presenting as subclinical hypothyroidism (SHypo) or subclinical hyperthyroidism (SHyper), defined as abnormal serum thyrotropin (TSH) and normal free thyroid hormones, is associated with increased cardiovascular (CV) risk and mortality. Depending on the degree of such dysfunction, atherosclerosis, coronary artery disease, heart failure and cardiac arrhythmias, predominantly atrial fibrillation, characterize both disorders and increase CV and total mortality compared to euthyroid persons. There are some differences in the mechanisms involved in the increased CV risk incurred by each type of STD, with more traditional CV risk factors clustered in SHypo than in SHyper, while the role of the TSH or its absence thereof, together with the respective, even subtle, changes incurred in thyroid hormone concentrations, seem to adversely influence the CV system in both types of STD. There is evidence that treatment of STD confers potential benefits by reducing CV events, however, no consensus has been reached due to lack of randomized controlled studies. Nevertheless, due to accumulating evidence from observational studies, many authorities agree that individuals with severe SHypo (TSH > 10 mIU/L) or grade 2 SHyper (TSH < 0.1 mIU/L) should receive treatment, mostly for the increased risk of CV morbidity and mortality. The evidence reviewed herein should alert and help the clinician to wake up to these two potentially alarming conditions of STD as they may confer serious CV complications, while their treatment appears quite beneficial.     

Schilddrüse und Blutdruck

Thyroid hormones have several well-recognized effects on the vasculature and heart, resulting in characteristic cardiovascular changes in thyroid disease, including an increase in blood pressure. In hyperthyroidism reduced systemic vascular resistance and increased blood volume lead to an enhanced preload, which, in association with reduced afterload, improved contractility, as well as increased β-adrenergic activity, results in isolated systolic hypertension based on enhanced stroke volume and cardiac output. In contrast, hypothyroidism causes increased systemic vascular resistance in association with decreased arterial compliance resulting in elevated diastolic blood pressure. Therefore in the evaluation of arterial hypertension secondary hypertension based on thyroid disease should always be considered, especially given the fact that blood pressure changes in the course of thyroid dysfunction are usually reversible upon adequate treatment of hypo- or hyperthyroidism.     

Hyperthyroidism: a "curable" cause of congestive heart failure--three case reports and a review of the literature

With the increasing incidence of coronary artery disease and the aging population, the prevalence of congestive heart failure (CHF) is increasing. In the majority of these cases the etiology is underlying coronary artery disease. Other less common causes of CHF include valvular heart disease, hypertension, alcoholic cardiomyopathy, and dilated cardiomyopathy. In addition, there are rare causes, one of which is hyperthyroidism. Hyperthyroidism can affect the cardiovascular system in a variety of ways. The cardiovascular manifestations range from sinus tachycardia to atrial fibrillation and from a high cardiac output state to CHF due to systolic left ventricular dysfunction. If the underlying hyperthyroidism is recognized and treated early the CHF in such cases can be cured. The authors present three cases of CHF due to systolic left ventricular dysfunction secondary to hyperthyroidism, which showed considerable improvement in the left ventricular function once the hyperthyroidism was treated.     

Reversible pulmonary hypertension, tricuspid regurgitation and right-sided heart failure associated with hyperthyroidism: case report and review of the literature

Primary pulmonary hypertension carries a grim prognosis, therefore, it is imperative that prior to reaching this diagnosis, a thorough search be made for all possible causes of pulmonary hypertension. An uncommon cause of pulmonary hypertension amenable to treatment may occasionally be identified. This case report describes a young woman who presented with rapidly progressive right heart failure. Work up for the common secondary causes of pulmonary hypertension was negative, including, congenital intracardiac shunts, left-sided atrial or ventricular heart disease, left-sided valvular heart disease, disorders of the respiratory system including hypoxemia and pulmonary thromboembolic and venoocclusive disease, collagen vascular disease, portal hypertension, HIV infection as well as pulmonary hypertension secondary to drugs and toxins. The only concurrent illness identified was Graves disease. After treatment of hyperthyroidism there was complete resolution of the right heart failure, tricuspid regurgitation, and the pulmonary hypertension. Only a few cases of reversible pulmonary hypertension and right heart failure associated with hyperthyroidism have been reported worldwide. In these patients, the most striking feature has been the normalization of the cardiovascular findings after adequate treatment of hyperthyroidism. The exact reasons for the development of pulmonary hypertension in hyperthyroidism are unclear. Proposed mechanisms include high cardiac output-induced endothelial injury, increased metabolism of intrinsic pulmonary vasodilating substances resulting in elevated pulmonary vascular resistance, and autoimmune phenomenon. Hyperthyroidism should be included in the causes of secondary pulmonary hypertension and/or otherwise unexplained right heart failure. This is especially important because hyperthyroidism is a treatable entity and its cardiac manifestations may be completely reversible.     

Pericardial effusion as an expression of thyrotoxicosis

Patients who have either hyperthyroidism or hypothyroidism can present with cardiovascular complications. These manifestations of thyroid disease-congestive heart failure, atrial tachyarrhythmias, atrioventricular conduction disorders, and mitral valve dysfunction-are well known to the clinician. Pericardial effusion is considered a complication of hypothyroidism; as an expression of thyrotoxicosis, it is extremely rare.Herein, we present the case of a 76-year-old woman who had pericardial effusion associated with thyrotoxicosis. She was treated with high-dose beta-blockers, methimazole, diuretics, and short-term steroids. She recovered completely, which precluded the need for pericardiocentesis. We suggest that thyrotoxicosis be considered in the differential diagnosis of pericardial effusion.     

Relationship of low-density lipoprotein (LDL) particle size to thyroid function status in Koreans

Objective  Dyslipidaemia is a well-known manifestation of thyroid dysfunction. Recently, small low-density lipoprotein (LDL) particle size has been linked with development of cardiovascular disease. To better understand the effects of thyroid dysfunction on the development of cardiovascular disease, we examined LDL particle size and lipid profiles in subjects with different thyroid function.
Methods  Included were 46 patients with overt hypothyroidism, 57 patients with subclinical hypothyroidism, 46 patients with overt hyperthyroidism, 51 patients with subclinical hyperthyroidism, and 110 age- and sex-matched healthy control subjects. We measured LDL particle size and lipid profiles in these subjects.
Results  No significant differences were found in LDL particle size between the groups with different thyroid function. Serum total cholesterol and LDL-cholesterol levels were significantly higher in the cases of hypothyroidism than in the cases of hyperthyroidism and the healthy control subjects. Serum triglyceride levels were higher in subjects with overt hypothyroidism than in those with overt hyperthyroidism or healthy control subjects.
Conclusions  LDL particle size, the emerging risk factor for atherosclerosis, did not appear to be significantly affected by the degree of thyroid dysfunction. Increased risk of atherosclerosis in hypothyroidism does not appear to be associated with LDL particle size, the non-traditional cardiovascular risk factor.     

The Systematic Screening and Management of Hypothyroidism and Hyperthyroidism During Pregnancy

Altogether, thyroid function abnormalities during pregnancy can affect up to 10% of all women. The high prevalence of both hypo- and hyperthyroidism, the obstetrical repercussions associated with thyroid dysfunction in the mothers, as well as the potential role of maternal thyroid dysfunction as an influence on fetal development constitute solid arguments for a further increase of our knowledge of the pathophysiological processes underlying the alterations of thyroid function related to the pregnant state. In this review, the focus will be on the most clinically relevant aspects associated with hypothyroidism [autoimmune thyroid disorders (AITDs), subfertility, risk of miscarriage, risk of hypothyroidism in women with AITD and treatment of hypothyroid women] and with hyperthyroidism (clinical presentations during pregnancy, Graves' disease and its management, fetal hyperthyroidism in women with antithyroid-stimulating hormone receptor antibodies and gestational transient thyrotoxicosis associated with human chorionic gonadotropin stimulation of the maternal thyroid gland). I also propose a global strategy for the systematic screening of hypo- and hyperthyroidism in the pregnant state.