Thyroid hormone and the cardiovascular system

Thyroid hormone has many effects on the heart and vascular system. In hyperthyroidism changes in cardiovascular hemodynamics explain many of the clinical manifestations induced by thyroid hormones. In hypothyroidism the cardiovascular effects are opposite to those observed in hyperthyroidism, although the clinical manifestations are less obvious. This review will focus on the cardiovascular system in hyperthyroidism and hypothyroidism. In particular the subclinical dysfunctions of the thyroid gland, which occurs especially in older age, will be discussed. The clinical relevance and the necessity of diagnostic and therapy in subclinical thyroid disease are not clarified yet. In the United States an expert group has published a scientific review and guideline for the diagnosis and management of subclinical thyroid disease in 2004, which will also be outlined.     

Subclinical thyroid dysfunction in the elderly.

Subclinical thyroid dysfunction is more common in older persons. By definition, these disorders are recognized by isolated elevation or suppression of the serum TSH concentration, in association with a normal serum free thyroxine level. Among individuals over 65 years old, subclinical hypothyroidism is found in approximately 10% of women and approximately 3% of men. It is most commonly due to autoimmune thyroiditis or previous treatment for hyperthyroidism. There may be three indications for L-thyroxine therapy: (a) presence of antithyroid antibodies, indicating substantial risk of progression to over hypothyroidism; (b) symptoms consistent with thyroid hormone deficiency; and (c) an elevated serum LDL-cholesterol. Subclinical hyperthyroidism is present in approximately 1%-2% of older persons. The most common cause is excessive thyroid hormone therapy, followed by mild endogenous hyperthyroidism due to Graves' disease or nodular goiter. These can be differentiated from other causes of low serum TSH concentration based on clinical and other laboratory and radionuclide scan criteria. The most serious consequences of subclinical hyperthyroidism are atrial fibrillation and osteoporosis, to which elderly patients are particularly predisposed.     

Approach to the patient with subclinical hyperthyroidism

Endogenous subclinical hyperthyroidism, defined by normal circulating levels of free T4 and T3 and low levels of TSH, is a common clinical entity and is typically caused by the same conditions that account for the majority of cases of overt hyperthyroidism: Graves' disease, toxic multinodular goiter, and solitary autonomously functioning thyroid nodules. Subclinical hyperthyroidism has been associated with an increased risk of atrial fibrillation and mortality, decreased bone mineral density in postmenopausal women, and mild hyperthyroid symptoms. Treatment of subclinical hyperthyroidism remains controversial, given the lack of prospective randomized controlled trials showing clinical benefit with restoration of the euthyroid state. Nevertheless, it seems reasonable to treat older individuals whose serum TSH levels are less than 0.1 mU/liter and certain high-risk patients, even when the serum TSH is between 0.1 and the lower limit of the normal range.     

糖尿病住院患者434例甲状腺疾病患病率分析

目的 探讨江苏地区糖尿病患者中甲状腺疾病的现患情况.方法 横向断面调查2006年10月至2007年6月于南京医科大学第一附属医院就诊的长期居住于江苏地区的434例糖尿病患者的甲状腺功能,其中109例患者作了甲状腺超声检查.结果 (1)糖尿病患者合并甲状腺疾病的患病率为23.27%,女性多见(P＜0.05),其中甲状腺功能减退者占16.36%(临床甲减4.15%,亚临床甲减12.21%),明显高于甲状腺功能亢进者6.91%(临床甲亢4.61%,亚临床甲亢2.30%),两者差异有统计学意义.(2)糖尿病患者中,甲状腺功能减退的患病率随患者年龄和糖尿病病程的增加而增加(P＜0.01);甲状腺功能亢进的患病率随糖尿病痛程的增加而降低(P＜0.05),随年龄的增加患病率改变无统计学意义.(3)糖尿病患者中甲状腺结节患病率为40.37%,性别差异无统计学意义,患病率随年龄的增加而增加(P＜0.05),不随糖尿病痛程的增加而增加.结论 糖尿病患者合并甲状腺疾病较常见,可能影响糖尿病患者的病情和预后,筛查和随访糖尿病患者的甲状腺功能及形态学状态具有重要的临床意义.     

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。     

Development of subclinical hyperthyroidism due to Graves' disease in a hypothyroid woman who had undergone hemithyroidectomy for adenomatous goiter and radiotherapy for nasopharyngeal cancer

A variety of thyroid disorders develop following external radiation to head and neck cancers. Hypothyroidism is the most common clinical consequence of the radiotherapy and lifelong thyroid hormone replacement is required in many cases. Patients who received both hemithyroidectomy and the external radiation to the neck are at especially high risk for permanent hypothyroidism. Here we report an unusual case with radiation-induced hypothyroidism who had undergone hemithyroidectomy for adenomatous goiter 8 years before the radiotherapy for nasopharyngeal cancer and subclinical hyperthyroidism due to Graves' disease developed during thyroxine replacement therapy. Thus subclinical hyperthyroidism due to Graves' disease can develop in patients with radiation-induced hypothyroidism even if they have undergone hemithyroidectomy for thyroid nodules. Therefore careful and periodic evaluation of thyroid function is required even on adequate thyroxine replacement therapy.     

Epidemiological survey on the relationship between different iodine intakes and the prevalence of hyperthyroidism

OBJECTIVE: To investigate the effect of different levels of iodine intake on the prevalence of hyperthyroidism and the impact of universal salt iodization on the incidence of hyperthyroidism. DESIGN: A comparative cross-sectional and longitudinal survey was conducted in three areas with borderline iodine deficiency, mild iodine excess (previously mild iodine deficiency) and severe iodine excess. Universal salt iodization had been introduced 3 years previously except in the area with borderline iodine deficiency. METHODS: In total 16 287 inhabitants from three areas answered a questionnaire concerning the history of thyroid disease. Among them 3761 unselected subjects received further investigations including thyroid function, thyroid autoantibodies, thyroid ultrasonography and urinary iodine excretion. RESULTS: Among areas with median urinary iodine excretion of 103 microg/l, 375 microg/l and 615 microg/l (P<0.05), the prevalence of hyperthyroidism did not differ significantly (1.6%, 2% and 1.2%). The prevalence of subclinical hyperthyroidism was higher in areas with borderline iodine deficiency and mild iodine excess than in the area with severe excess iodine intake (3.7%, 3.9% and 1.1%, P<0.001). The prevalence of Graves' disease and its proportion in hyperthyroidism did not differ among areas. The incidence of hyperthyroidism did not significantly increase after the introduction of universal salt iodization. CONCLUSION: Different iodine intakes under a certain range do not affect the prevalence and type of hyperthyroidism. Subclinical hyperthyroidism is more prevalent in the iodine deficient area than in the severe iodine excessive area. In the area with mild iodine deficiency, the introduction of universal salt iodization may not be accompanied by an increased incidence of hyperthyroidism.     

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.     

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.     

Subclinical hyperthyroidism in patients with type 2 diabetes

Both subclinical hyperthyroidism and type 2 diabetes (T2D) have been associated with an increase in cardiovascular disease risk and mortality. We aimed to assess the prevalence of newly diagnosed subclinical hyperthyroidism in a cohort of patients with T2D, and also to analyse the relationships between diabetes-related characteristics and the presence of subclinical hyperthyroidism. 933 diabetic patients without previous history of thyroid disease (45.4% females, mean age 66.3 years, median duration of diabetes 10 years) were evaluated. A sample of 911 non-diabetic subjects without known thyroid dysfunction was studied as control group. Serum concentrations of thyrotropin were measured in all subjects. Subclinical hyperthyroidism was present in 4.3% of female and 3.5% of male diabetic patients. Relative risk was significant only for the female gender (OR 3.69, 95% CI 1.56-8.71). In comparison with diabetic patients without thyroid hyperfunction, patients with subclinical hyperthyroidism were older, had longer duration of diabetes, showed lower fasting glucose levels, had greater proportion of goitre and diet therapy, and had lower proportion of treatment with oral agents. Logistic regression analysis showed that age and the presence of goitre were significantly related to subclinical hyperthyroidism in patients with T2D. The risk for subclinical hyperthyroidism is increased in women with T2D. Advanced age and the presence of goitre are significantly and independently related with the presence of subclinical hyperthyroidism in diabetic population.     

A clinical and therapeutic approach to thyrotoxicosis with thyroid-stimulating hormone suppression only

Subclinical hyperthyroidism is defined as normal serum free thyroxine (T4) and triiodothyronine (T3) concentrations and persistently suppressed thyroid stimulating hormone (TSH) concentrations. The most common cause of subclinical hyperthyroidism is the use of suppressive doses of L-thyroxine for treatment of hypothyroidism or, less commonly, diffuse nontoxic goiter or thyroid carcinoma (exogenous subclinical hyperthyroidism). Endogenous subclinical hyperthyroidism may be caused by a variety of thyroid disorders that result in overproduction and release of thyroid hormones from the gland with normal/high 24-hour thyroid radioiodine uptake or by inflammation in the thyroid resulting in release of excess thyroid hormones and low 24-hour thyroid radioiodine uptake. Several groups have investigated whether persistent endogenous or exogenous subclinical hyperthyroidism, like overt hyperthyroidism, causes symptoms, adverse effects on the cardiovascular and the skeletal systems, and increased mortality, whether endogenous subclinical hyperthyroidism evolves to overt thyrotoxicosis, and whether or not it should be treated. The present report reviews the most important and recent studies of subclinical hyperthyroidism and attempts to draw conclusions based upon the literature and the authors' experience.     

Radioiodine treatment for benign thyroid disorders: results of a nationwide survey of UK endocrinologists

Background A survey of physicians’ practice relating to radioiodine administration for hyperthyroidism was carried out in the UK over 15 years ago and showed wide variations in patient management. This led to the development of national guidelines for the use of radioiodine in hyperthyroidism. As there have been significant advances in the field since that survey, we carried out another survey to study the prevalent practices relating to radioiodine therapy for benign thyroid disorders across the UK. Subjects and methods We mailed 698 UK consultant endocrinologists a questionnaire on radioiodine treatment based on three patient scenarios: hyperthyroid Graves’ disease, subclinical hyperthyroidism and nontoxic goitre. Results The response rate was 40%. For the scenario of an initial presentation of Graves’ disease, 80%, 19% and 0·4% of respondents preferred thionamide, radioiodine or thyroidectomy, respectively. There were inconsistencies in respondents’ recommendations on radioiodine dose, the use of pre‐ and post‐radioiodine supplementary treatments, timing of a repeat dose, and the use of radioiodine in thyroid eye disease. For the case of subclinical hyperthyroidism, one‐third of respondents would generally initiate treatment. The majority were more likely to treat subclinical hyperthyroidism in the presence of paroxysmal atrial fibrillation or osteoporosis. If a decision were made to treat subclinical hyperthyroidism, 63%, 35%, 1% and 0·4% would recommend radioiodine, thionamide, beta‐blocker and thyroidectomy, respectively. For the scenario of nontoxic goitre, 62%, 21%, 13% and 5% favoured observation, thyroidectomy, radioiodine and thyroxine, respectively. Conclusions There remain significant differences in several aspects of clinical practice relating to the use of radioiodine treatment for benign thyroid disorders in the UK.     

Thoughts on prevention of thyroid disease in the United States.

In the realm of preventive medicine, there are three distinct types of prevention that can be defined. Primary prevention is the prevention of new disease in previously healthy individuals, usually achieved by decreasing risk factors for disease. Secondary prevention is the prevention of progression of mild or latent disease to more severe disease, and typically involves screening for occult disease. Tertiary prevention is the term used by some to describe medical care intended to improve already established disease. The role of primary prevention of thyroid disease in the United States is uncertain, because iodine deficiency is not clearly known to be a problem. In the case of secondary prevention of thyroid disease, this would necessarily involve screening of individuals for subclinical hyperthyroidism or hypothyroidism with thyrotropin (TSH) testing. Using data from a large prevalence study and from the 2000 U.S. Census, it can be calculated that approximately 15 million adults have unrecognized thyroid disease, mostly subclinical hypothyroidism. If detected, secondary prevention might also entail treatment with antithyroid drugs/radioiodine or thyroxine to prevent sequelae or progression to a more advanced degree of thyrotoxicosis or thyroid failure, respectively. Over the next 20 years, it can be calculated that approximately 5 million people, mostly with subclinical hypothyroidism, will progress to overt disease. Tertiary prevention of thyroid disease would involve avoiding iatrogenic disease, such as thyroid hormone overdose. From epidemiologic data it can be calculated that approximately 600,00 elderly individuals have iatrogenic hyperthyroidism from thyroid hormone overdose, putting them at risk for atrial fibrillation and osteoporosis. Together, these data suggest that the notion of preventive medicine in the United States should be expanded to include thyroid disease as a target for secondary and tertiary intervention.     

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.     

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.     

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.     

Subclinical thyroid diseases

Subclinical thyroids disease (STD) is recently defined term in clinical thyroidology, which includes mainly functional disorders. Basic diagnostic signs are: normal values of thyroid hormones (fT4, fT3) and elevated TSH level (subclinical hypothyroidism) or suppresed TSH level (subclinical hyperthyroidism). In a category of STD may be included subclinical autoimunne thyroiditis (elevated level of thyroid antigens antibodies and/or hypoechogenity in sonographic screen, increased volume of the thyroid without clinical symptoms and/or autoimminity) and microscopic lesions of papillary thyroid carcinoma. Subclinical hypothyroidism may be dangerous for tendency to development of manifest hypothyroidism and for risk of disorders of lipid profile and development of atherosclerosis and its organ complication (esp. myocardial infarction). Subclinical hyperthyroidism is a risk factor of cardiac arythmias and probably can increase a risk of cardiovascular mortality) as well for osteoporosis (esp. in peri- and post-climacteric women), and last but not least for degenerative diseases of brain (?). Indication of treatment of STD is a matter of controversies. Recomendations of experts, varied from "no therapy, monitoring only" to "treat always". Treatment of risk groups (esp. pregnant women) is probably nowadays a most rationale recommendations since results of sofisticated prospective studies will be available.     

Prevention and multimodal therapy of hyperthyroidism

Subclinical and overt hyperthyroidism have been associated with various negative clinical outcomes as for example an increased risk of atrial fibrillation or increased cardiovascular mortality, especially in old age. In order to avoid hyperthyroidism it is strongly recommended not to start any iodine containing drug therapy or to avoid application of contrast agents unless the patient presents with an unremarkable clinical course. TSH suppressive therapy for the treatment of endemic goiter or differentiated low risk thyroid carcinoma is unnecessary, since it favours the development of subclinical hyperthyroidism. Overt hyperthyroidism is treated with antithyroid drugs and/or radioiodine therapy or surgery according to the underlying disease (toxic nodular goiter, Graves' disease).     

The evaluation of left ventricular hypertrophy in hypertensive patients with subclinical hyperthyroidism

The aim of this prospective cross-sectional study was to investigate the hypertrophic effects of endogenous subclinical hyperthyroidism on myocardium and early development of left ventricular hypertrophy (LVH) in essential hypertensive patients accompanied by endogenous subclinical hyperthyroidism. A total of 31 consecutive patients with stage I hypertension were included in the study. Sixteen of them also had endogenous subclinical hyperthyroidism that they were unaware before. The patients and the controls formed out of ten healthy subjects all underwent an investigation of thyroid functions and cardiologic evaluation. The mean wall thickness of the left ventricle in the stage I hypertensive group with endogenous subclinical hyperthyroidism (group I) was significantly increased as compared with both hypertensive patients without thyroid disease (group II) and the control subjects. The mean left ventricle mass was also significantly higher in group I than group II. Both of the patients' groups had an increased prevalence of LVH as compared with the controls. In this study, hypertensive patients with subclinical hyperthyroidism presented more increase in left ventricular mass, suggesting that subclinical hyperthyroidism may contribute to left ventricular hypertrophy forming a natural progression to hypertension. The hypertensive population should always be screened for endogenous subclinical hyperthyroidism, and should be examined for the criteria of left ventricular hypertrophy by echocardiography in early stages.