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.     

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.     

Subclinical Thyroid Disease

Subclinical thyroid disease, a term applied to patients with no or minimal thyroid-related symptoms with abnormal laboratory values, is diagnosed more frequently with the use of thyroid-stimulating hormone (TSH) screening and newer high-sensitivity assays. These are laboratory diagnoses, with subclinical hypothyroidism defined as an elevated TSH with a normal free thyroxine and triiodothyronine concentration, and subclinical hyperthyroidism as a subnormal TSH with normal free thyroxine and triiodothyronine levels. Although studies defining which patients require treatment are few, decisions should be individualized based upon laboratory values and symptoms. This article reviews the etiologies, diagnoses, treatments and indications, and monitoring of patients with subclinical thyroid disease.     

Atrial fibrillation associated with subclinical hyperthyroidism

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. We present a case of atrial fibrillation associated with subclinical hyperthyroidism, in a 78-year-old Italian woman. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism.     

The Prevalence and Prognostic Effects of Subclinical Thyroid Dysfunction in Dilated Cardiomyopathy Patients: A Single-Center Cohort Study

BackgroundSubclinical thyroid dysfunction may be a risk factor for mortality in patients with heart failure and may be associated with dilated cardiomyopathy (DCM). This was a cohort study to examine the possible association between subclinical thyroid dysfunction and all-cause mortality in DCM patients, because the current evidence on this association remains elusive.Methods and ResultsA total of 963 DCM patients were evaluated for thyroid function. Of these patients, 7.1% (n = 68) had subclinical hyperthyroidism (defined as serum thyroid-stimulating hormone [TSH] <0.35 μIU/mL), 84.7% (n = 816) had euthyroidism (TSH 0.35-5.5 μIU/mL), and 8.2% (n = 79) had subclinical hypothyroidism (TSH >5.5 μIU/mL). There was a significant difference in all-cause mortality rates between patients with euthyroidism and patients with subclinical hyper- and hypothyroidism (21%, 38.2%, and 26.6%, respectively; log-rank χ² = 13.104; P = .001) with mean follow-up of 3.5 years. After adjustment for other confounding factors at baseline, QRS duration, N-terminal pro–B-type natriuretic peptide, New York Heart Association functional class, left atrial diameter, and subclinical hyperthyroidism (hazard ratio 1.793, 95% CI 1.010–3.183; P = .046) emerged as significant predictors of all-cause mortality.ConclusionDCM patients with subclinical hyper- and hypothyroidism had higher all-cause mortality rates. However, only subclinical hyperthyroidism, not subclinical hypothyroidism, was an independent predictor for increased risk of all-cause mortality.     

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.     

Intermittent changing axis deviation with intermittent left anterior hemiblock during atrial flutter with subclinical hyperthyroidism

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 CHD or mortality from cardiovascular causes but it is usually associated with a higher heart rate and a higher risk of supraventricular arrhythmias including atrial fibrillation and atrial flutter. Intermittent changing axis deviation during atrial fibrillation has also rarely been reported. We present a case of intermittent changing axis deviation with intermittent left anterior hemiblock in a 59-year-old Italian man with atrial flutter and subclinical hyperthyroidism. To our knowledge, this is the first report of intermittent changing axis deviation with intermittent left anterior hemiblock in a patient with atrial flutter.     

Characterization of subclinical thyroid dysfunction from cardiovascular and metabolic viewpoints: the Suita study.

BACKGROUND: Subclinical hypothyroidism, defined as high serum thyroid-stimulating hormone (TSH) levels and normal serum free-triiodothyronine (fT3) and serum free-thyroxine (fT4) levels, is a common medical problem among the elderly, but it is unclear whether it should be treated with thyroid hormone replacement therapy. METHODS AND RESULTS: A cross-sectional study of 3,607 participants in a community health survey in Suita, in the northern part of Osaka, was performed. Participants were categorized into 5 groups: normal, hyperthyroidism, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism. The association between each group and various phenotypes was examined, in relation to cardiovascular disease and metabolic syndromes. Serum TSH levels increased and fT3 and fT4 levels decreased with age. A total of 14.6% of subjects aged 70-80 years and 20.1% of subjects aged older than 80 years were classified as having subclinical hypothyroidism. Subclinical hypothyroidism was not associated with glycol-hemoglobin A1c, body mass index, pulse rate, hypertension, total cholesterol, high-density lipoprotein cholesterol or triglyceride levels or intima-media thickness. It was only associated with higher fasting blood glucose and glycol-hemoglobin A1c levels compared with euthyroidism. CONCLUSIONS: The present observation does not support the need for treatment of subclinical hypothyroidism or subclinical hyperthyroidism.     

Mortality rate of chronically ill geriatric patients with subnormal serum thyrotropin concentration: a 2-yr follow-up study

We investigated the natural course of subclinical thyroid dysfunctions in geriatric patients, especially regarding their association with mortality rate. Ninety-three randomly selected chronically ill geriatric patients 64–87 (median: 77) yr of age participated in the screening study with a 2-yr follow-up. Serum thyrotropin (thyroid-stimulating hormone [TSH]), free thyroxine, triiodothyronine, and antibodies against thyroid peroxidase were measured. During the follow-up, patients with suppressed TSH levels who were otherwise euthyroid (untreated) had a higher mortality rate than patients with normal TSH (5/8 vs 18/64; p<0.05). The initial clinical state of these two subgroups did not differ significantly. Two-thirds of patients with treated hyperthyroidism died. The mortality rate of patients with initially subnormal but not suppressed TSH level was average and did not differ statistically from either the euthyroid or the hyperthyroid groups. Only 1 of 13 euthyroid patients with positive thyroid antibody titers developed a subsequent subclinical hypothyroidism. Subclinical hyperthyroidism was found to be associated with a higher mortality rate in chronically ill geriatric patients, which justifies screening for thyroid dysfunction and treatment of subclinical hyperthyroidism. In addition, a subnormal but measurable TSH was not indicative regarding the future development of hyperthyroidism. Finally, during the 2-yr follow-up, antibody positivity in the euthyroid cases did not prove to be predictive for the subsequent development of hypothyroidism.     

Paroxysmal atrial fibrillation during acute myocardial infarction associated with subclinical hyperthyroidism, severe three vessels coronary artery disease and elevation of prostate-specific antigen after TURP

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. Paroxysmal atrial fibrillation is a frequent complication of acute myocardial infarction. It has been reported that subclinical hyperthyroidism is not associated with CHD or mortality from cardiovascular causes but it is sufficient to induce an increase in atrial fibrillation rate and increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. It has also been reported that serum prostate-specific antigen (PSA) decreases drastically in patients who undergo transurethral resection of the prostate(TURP). We present a case of paroxysmal atrial fibrillation during acute myocardial infarction associated with subclinical hyperthyroidism, severe three vessels coronary artery disease and elevation of PSA after TURP in a 78-year-old Italian man.     

亚临床甲状腺功能减退症

亚临床甲状腺功能减退症(甲减)是一种业临床甲状腺疾病.诊断标准是血清促甲状腺激素(TSH)水平高于正常上限而游离T4水平尚在正常范围.目前全世界业临床甲减的平均患病率为4%～10%,主要发生在女性和老年人群.桥本甲状腺炎是最常见的病因.其卡要的临床危害包括引起血脂异常、导致动脉粥样硬化和,冠心病、影响认知功能,还可导致不孕和流产.治疗主要针对血清TSH10 mIU/L的患者,应用左旋-T4替代治疗.对于血清TSH 4～10 mIU/L,特别是甲状腺自身抗体阳性者需密切监测.此外,对妊娠期亚临床甲减患者的治疗要求控制TSH<2.5 mlU/L.     

亚临床甲状腺功能减退症

亚临床甲状腺功能减退症（甲减）是一种亚临床甲状腺疾病。诊断标准是血清促甲状腺激素（TSH）水平高于正常上限而游离T4水平尚在正常范围。目前全世界亚临床甲减的平均患病率为4％-10％,主要发生在女性和老年人群。桥本甲状腺炎是最常见的病因。其主要的临床危害包括引起血脂异常、导致动脉粥样硬化和冠心病、影响认知功能,还可导致不孕和流产。治疗主要针对血清TSH〉10ml U／L的患者,应用左旋-T4替代治疗。对于血清TSH4～10ml U／L,特别是甲状腺自身抗体阳性者需密切监测。此外,对妊娠期亚临床甲减患者的治疗要求控制TSH〈2．5ml U／L。     

Recognition and management of cardiovascular disease related to thyroid dysfunction

Hypothyroidism and hyperthyroidism are both associated with clinically significant cardiovascular derangements. In hypothyroidism, these include pericardial effusion, heart failure, and the complex interrelationship between hypothyroidism and ischemic heart disease. Cardiovascular disorders associated with hyperthyroidism include atrial tachyarrhythmias, mitral valve dysfunction, and heart failure. Although these usually occur in individuals with intrinsic heart disease, thyroid dysfunction alone rarely causes serious but reversible cardiovascular dysfunction. Patients with commonly encountered cardiac disorders, e.g., idiopathic cardiomyopathy and atrial fibrillation, should be screened for potentially contributing subclinical thyroid diseases. In patients with heart failure and hypothyroidism, initial management should focus on diagnosis and optimal management of any primary cardiac disease, whereas in hyperthyroidism, aggressive measures to control excess thyroid hormone action should generally have the highest priority.     

Subclinical hypothyroidism,lipid metabolism and cardiovascular disease

Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10 mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism.     

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.     

Acute myocardial infarction and subclinical hyperthyroidism without significant coronary stenoses

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 CHD or mortality from cardiovascular causes but increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. It has been also reported an acute myocardial infarction with normal coronary arteries associated with iatrogenic hyperthyroidism and with a myocardial bridge too. Moreover, it has been reported that simply measuring maximum P wave duration and P wave dispersion values, may help to determine the patients with subclinical hyperthyroidism and high risk for the development of atrial fibrillation. We present a case of an acute myocardial infarction without significant coronary stenoses associated with subclinical hyperthyroidism. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism.     

Does Treating Subclinical Hypothyroidism Improve Markers of Cardiovascular Risk?

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.     

Paroxysmal ventricular tachycardia and paroxysmal atrial fibrillation associated with subclinical hyperthyroidism, chronic renal failure and elevation of prostate-specific antigen during acute myocardial infarction

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. Paroxysmal atrial fibrillation is a frequent complication of acute myocardial infarction. 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 an increase in atrial fibrillation rate. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Moreover chronic renal failure presents an increased arrhythmic risk. Apparently spurious result has been reported in a work about mean serum prostate-specific antigen (PSA) concentration during acute myocardial infarction with mean serum PSA concentration significantly lower on day 2 than either day 1 or day 3 and it has been reported that these preliminary results could reflect several factors, such as antiinfarctual treatment, reduced physical activity or an acute-phase response. We present a case of paroxysmal ventricular tachycardia and paroxysmal atrial fibrillation associated with subclinical hyperthyroidism, chronic renal failure and elevation of serum PSA concentration in a 90-year-old Italian man during acute myocardial infarction. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism and of chronic renal failure. Moreover, our report also confirms previous findings and extends the evaluation of PSA during acute myocardial infarction.