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.     

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.     

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).     

Cardiovascular symptoms and risks of subclinical dysthyroidism

PURPOSE: To clarify the importance of cardiovascular symptoms and risks in subclinical dysthyroidism in order to define the best way of treatment and follow-up. CURRENT KNOWLEDGE AND KEY POINTS: Subclinical dysthyroidism is defined by abnormal circulating TSH values in face and normal free thyroid hormones levels, in asymptomatic individuals. If the cardiovascular effects of overt hyperthyroidism are well documented, the relation between subclinical dysthyroidism and the heart is not well established. Subclinical hyperthyroidism may be caused by the same thyroid disorders that results in overt hyperthyroidism, but the most common cause is excessive dosage in levothyroxine. The most frequent cardias complication of subclinical hyperthyroidism is atrial fibrillation. Recently minimal alterations of myocardial function have also been described. In most patients, one tries to return to euthyroidism in order to prevent cardiovascular complications. Subclinical hypothyroidism is 3 to 10 times more frequent, especially in women after 60 years. Subtle modifications of cardiac function and lipid metabolism and an increased risk of atherosclerosis have been described in this condition. There is still debate about the decision to treat or not to treat these patients. FUTURE PROSPECTS AND PROJECTS: Until now, treatment of subclinical dysthyroidism is mainly based upon experiences and convictions to physicians. Prospective studies are necessary to assess the true benefits and risks of either early treatment or therapeutic abstention with regular clinical and biological follow up. In such studies, patients should be separated according to age and the nature (endogenous or exogenous) of dysthyroidism.     

Prävention und multimodale Therapie der Hyperthyreose

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).     

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.     

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.     

亚临床甲状腺疾病与缺血性卒中的风险和转归

亚临床甲状腺疾病包括亚临床甲状腺功能减退和亚临床甲状腺功能亢进,以后者更常见。亚临床甲状腺疾病可能导致高血压、糖尿病、血脂异常、动脉粥样硬化、心房颤动、高同型半胱氨酸血症等血管危险因素的发生率显著增高,同时与急性缺血性卒中的转归可能有关。     

How could we improve the increased cardiovascular mortality in patients with overt and subclinical hyperthyroidism?

Over the past five years several meta-analyses have evaluated the cardiovascular mortality in patients with hyperthyroidism. They assessed various studies in which different inclusion criteria were used for the analysis of the cardiovascular mortality. More selective criteria have been used in recent meta-analyses. Only prospective cohort studies were included and only cohorts using second and third generation TSH assays were chosen. In addition, only the studies where the TSH evaluation was repeated during the follow-up were selected. The results of these recent meta-analyses provide evidence that overt and subclinical hyperthyroidism, particularly in patients with undetectable serum TSH, may increase the cardiovascular mortality. However, still today, the results remain inconclusive and not sufficient enough to recommend treatment for patients with low-detectable serum TSH. The high cardiovascular risk and mortality in presence of thyroid hormone excess suggest that this dysfunction is an important health problem and requires guidelines for the treatment of patients at high cardiovascular risk. Rigorous studies are necessary to evaluate the effects of the various causes of hyperthyroidism on the clinical outcomes. Randomized controlled clinical trials are needed to assess the benefits of treatment to improve the cardiovascular mortality and morbidity of mild and overt hyperthyroidism.     

Graves’ disease,multinodular goiter and subclinical hyperthyroidism

Subclinical hyperthyroidism is a common clinical entity, defined by serum TSH below the reference range, with normal FT4 and FT3 levels in an asymptomatic patient. Whether or not subclinical hyperthyroidism should be treated remains a matter of debate. Cross-sectional and longitudinal population-based studies demonstrate association of subclinical hyperthyroidism with risk of atrial fibrillation and osteoporosis, and with cardiovascular and all-cause mortality. However, there are no randomized clinical trials addressing whether long-term health outcomes are improved by treating subclinical hyperthyroidism; in the absence of evidence one way or the other, it seems appropriate to use decision trees taking account of TSH concentration and presence of risk factors (age > 65 years or post-menopause, osteoporosis and cardiac disease).     

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.     

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.     

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.     

Subclinical hyperthyroidism: clinical features and treatment options

Subclinical hyperthyroidism appears to be a common disorder. It may be caused by exogenous or endogenous factors: excessive TSH suppressive therapy with L-thyroxine (L-T4) for benign thyroid nodular disease, differentiated thyroid cancer, or hormone over-replacement in patients with hypothyroidism are the most frequent causes. Consistent evidence indicates that 'subclinical' hyperthyroidism reduces the quality of life, affecting both the psycho and somatic components of well-being, and produces relevant signs and symptoms of excessive thyroid hormone action, often mimicking adrenergic overactivity. Subclinical hyperthyroidism exerts many significant effects on the cardiovascular system; it is usually associated with a higher heart rate and a higher risk of supraventricular arrhythmias, and with an increased left ventricular mass, often accompanied by an impaired diastolic function and sometimes by a reduced systolic performance on effort and decreased exercise tolerance. It is well known that these abnormalities usually precede the onset of a more severe cardiovascular disease, thus potentially contributing to the increased cardiovascular morbidity and mortality observed in these patients. In addition, it is becoming increasingly apparent that subclinical hyperthyroidism may accelerate the development of osteoporosis and hence increased bone vulnerability to trauma, particularly in postmenopausal women with a pre-existing predisposition. Subclinical hyperthyroidism and its related clinical manifestations are reversible and may be prevented by timely treatment.     

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.     

Thyroid Function Abnormalities and Cognitive Impairment in Elderly People: Results of the Invecchiare in Chianti Study

OBJECTIVES: To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition.
DESIGN: Cross-sectional.
SETTING: Community-based.
PARTICIPANTS: One thousand one hundred seventy-one men and women aged 23 to 102.
MEASUREMENTS: Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs ≥65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders.
RESULTS: Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P <.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P <.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61±6.88 vs 24.72±4.52, P <.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P =.003).
CONCLUSION: Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.     

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.     

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.