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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Is heart failure an endocrine disease? Historically, congestive heart failure (CHF) has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, as well as the activation of natriuretic peptides, endothelin and vasopressin, play key roles in the progression of CHF. In this context, agents targeting neurohormones offer a highly rational approach to CHF management, with ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving the prognosis for many patients. Although relevant improvements in clinical status and survival can be achieved with these drug classes, mortality rates for patients with CHF are still very high. Moreover, most patients do not receive these proven life-prolonging drugs, partially due to fear of adverse events, such as hypotension (with ACE inhibitors), gynaecomastia (with spironolactone) and fatigue (with beta-blockers). New agents that combine efficacy with better tolerability are therefore needed. The angiotensin II type 1 (AT(1))-receptor blockers have the potential to fulfil both these requirements, by blocking the deleterious cardiovascular and haemodynamic effects of angiotensin II while offering placebo-like tolerability. As shown with candesartan, AT(1)-receptor blockers also modulate the levels of other neurohormones, including aldosterone and atrial natriuretic peptide (ANP). Combined with its tight, long-lasting binding to AT(1)-receptors, this characteristic gives candesartan the potential for complete blockade of the RAAS-neurohormonal axis, along with the great potential to improve clinical outcomes.
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PMID:Neurohumoral blockade in CHF management. 1196 92

From the clinical standpoint a cardiomyopathy can be classified as primitive when other causes, i.e. ischemic, infiltrative, systemic diseases, can be ruled out. Initial symptoms usually include a progressive dyspnea and fatigue with tachycardia in a patient previously healthy. Congestive heart failure may be the initial manifestation. Angina is often present, not only because of coronary heart disease. Auscultatory findings usually include a gallop rhythm with a third heart sound, not rarely a four-sound gallop. Blood test to evaluate renal and liver function should be performed. The dosage of troponin I and/or troponin T, plasma renin activity, brain natriuretic peptide or endothelins has recently gained some reputation to indicate prognosis, but there is no reason to believe that these measures are superior to cardiopulmonary stress test.
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PMID:[Dilated cardiomyopathy: role of clinical and laboratory evaluation]. 1202 82

Cachexia, i.e. body wasting, has long been recognised as a serious complication of chronic illness. The occurrence of wasting in chronic heart failure (CHF) has been known for many centuries, but it has not been investigated extensively until recently. Cardiac cachexia is a common complication of CHF which is associated with poor prognosis, independently of functional disease severity, age, measures of exercise capacity, and left ventricular ejection fraction. Patients with cardiac cachexia suffer from generalised loss of lean tissue, fat tissue, as well as bone tissue. Cachectic CHF patients are weaker and fatigue earlier. This is due to both reduced skeletal muscle mass and impaired skeletal muscle quality. Concerning the pathophysiology of cardiac cachexia, there is increasing evidence that neurohormonal and immune abnormalities may play a crucial role. Cachectic CHF patients have raised plasma levels of norepinephrine, epinephrine, and cortisol, and they show high plasma renin activity and increased plasma aldosterone levels. A number of studies have also shown that cardiac cachexia is linked to raised plasma levels of inflammatory cytokines, such as tumor necrosis factor alpha. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems, termed catabolic/anabolic imbalance, is likely to be responsible for the development of the wasting process. It is hoped that a better understanding of the pathophysiological mechanisms involved in cardiac cachexia will lead to novel therapeutic strategies in the (near) future.
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PMID:The syndrome of cardiac cachexia. 1216 9

Although several investigations on mitral valve prolapse syndrome (MVPS) have been performed, clinical symptoms of this syndrome are not yet clarified. Atypical chest pain, palpitations, fatigue, dyspnea and anxiety are the most frequent symptoms associated with this syndrome. However, dizziness and syncope may be serious symptoms in MVPS. Dizziness and syncope are related to cardiac arrhythmias and are proposed to distinguish types, frequency of arrhythmias and relation to the symptoms. Orthostatic hypotension and tachycardia rarely occur in MVPS. The physiopathological mechanisms of these symptoms are not known clearly, but multifactorial causes are thought to be responsible including autonomic dysfunction, hyperadrenergic state, abnormalities in regulation of baroreceptors, parasympathetic derangements, decrease of intravascular volume, abnormal renin-aldosterone response to depletion of intravascular volume and abnormal release of atrial natriuretic factor.
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PMID:[Mitral valve prolapse syndrome: orthostatic hypotension and physiopathology of its clinical symptomathologies]. 1262 13

About 3% of our hypertensive patients have high blood pressure induced by corticosteroids. Muscle weakness, tiredness, polyuria and polydipsia may indicate hypokalaemia. Hypokalaemic hypertension in the presence of a low plasma renin activity is the typical finding of corticosteroid hypertension. The most frequent cause of corticosteroid hypertension is primary aldosteronism (Conn's syndrome) due to an adrenal adenoma or bilateral hyperplasia of the adrenal glands. The plasma concentration of aldosterone and the ratio between plasma aldosterone and renin concentrations are high, and the kaliuresis exceeds 30 mmol/24 h in the presence of hypokalaemia. Adrenal carcinomas are rare and very malignant. The localization of an adrenal tumour is made by computer tomography (CT-scan) or nuclear magnetic resonance imaging and by measurement of the aldosterone/cortisol concentrations in the adrenal venous blood. Adenomas are removed under laparoscopy, and adrenal hyperplasias are treated with spironolactone (50-400 mg daily) or amiloride (5-30 mg daily). In rare cases (<1%), excessive stimulation of the mineralocorticoid receptor is due to cortisol (apparent mineralocorticoid excess, Cushing's disease, liquorice, or hereditary deficiency of 11beta-hydroxysteroid dehydrogenase) or to a chimeric gene coding for 11beta-hydroxylase (CYP11B1/CYP11B2). In these rare cases, the synthesis of aldosterone is under the control of the adrenocorticotrophic hormone, so treatment with glucocorticoids (dexamethasone 0.25-1.0 mg daily) is therefore possible (glucocorticoid-remediable aldosteronism). Excessive deoxycorticosterone (DOC) causes the same symptoms and signs as hyperaldosteronism. Excessive DOC is found in patients with adrenal tumours that secrete DOC, in those with hereditary or acquired disorders with dysfunctioning glucocorticoid receptors, or in those with congenital hyperplasia of the adrenal glands (deficiency of 17alpha-hydroxylase or 11beta-hydroxylase). Liddle's syndrome is a constitutive hyperactivity of the transepithelial transport of sodium, which under normal conditions is controlled by the mineralocorticoid receptor. Plasma renin and aldosterone concentrations are suppressed and the plasma potassium concentration may be normal. In contrast, plasma aldosterone and renin concentrations are increased in patients with hypokalaemic hypertension which represents secondary aldosteronism. The increased aldosterone is the consequence of stimulated renin activity due to renal or renovascular or other disorders, antihypertensive drugs or other medications. In conclusion, a work-up for corticosteroid-induced hypertension is indicated in patients with hypokalaemic hypertension and in those with severe hypertension even in the absence of hypokalaemia, and in hypertensive patients with a family history of cardiovascular diseases.
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PMID:Investigating mineralocorticoid hypertension. 1292 4

In order to understand the mechanisms of exercise intolerance and muscle fatigue, which are commonly observed in congestive heart failure, we studied sarcoplasmic reticulum (SR) Ca(2+)-transport in the hind-leg skeletal muscle of rats subjected to myocardial infarction (MI). Sham-operated animals were used for comparison. On one hand, the maximal velocities (Vmax) for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities in skeletal muscle of rats at 8 weeks of MI were higher than those of controls. On the other hand, the Vmax values for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities were decreased significantly at 16 weeks of MI when compared with controls. These alterations in Ca(2+)-transport activities were not associated with any change in the affinity (1/Ka) of the SR Ca(2+)-pump for Ca2+. Furthermore, the stimulation of SR Ca(2+)-stimulated ATPase activity by cyclic AMP-dependent protein kinase was not altered at 8 or 16 weeks of MI when compared with the respective control values. Treatment of 3-week infarcted animals with angiotensin-converting enzyme (ACE) inhibitors such as captopril, imidapril, and enalapril or an angiotensin receptor (AT1R) antagonist, losartan, for a period of 13 weeks not only attenuated changes in left ventricular function but also prevented defects in SR Ca(2+)-pump in skeletal muscle. These results indicate that the skeletal muscle SR Ca(2+)-transport is altered in a biphasic manner in heart failure due to MI. It is suggested that the initial increase in SR Ca(2+)-pump activity in skeletal muscle may be compensatory whereas the depression at late stages of MI may play a role in exercise intolerance and muscle fatigue in congestive heart failure. Furthermore, the improvements in the skeletal muscle SR Ca(2+)-transport by ACE inhibitors may be due to the decreased activity of renin-angiotensin system in congestive heart failure.
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PMID:Changes in skeletal muscle SR Ca2+ pump in congestive heart failure due to myocardial infarction are prevented by angiotensin II blockade. 1538 90

Primary hyperparathyroidism (pHPT), caused by solitary parathyroid adenomas in 85% of cases and diffuse hyperplasia in most of the remaining cases, overproduces parathyroid hormone (PTH), which mobilizes calcium to the blood stream. Renal stones, osteoporosis and diffuse symptoms of hypercalcaemia, such as constipation, fatigue and weakness are well-known complications. However, in Western Europe and North America, patients with pHPT are nowadays usually discovered during an early, asymptomatic phase of the disease. It has been reported that patients suffering from symptomatic pHPT have increased mortality, mainly due to an overrepresentation of cardiovascular death. pHPT is reported to be associated with hypertension, disturbances in the renin-angiotensin-aldosterone system, and structural and functional alterations in the vascular wall. Recently, studies have indicated an association between pHPT and heart disease, and studies in vitro have produced a number of theoretical approaches. An increased prevalence of cardiac structural abnormalities such as left ventricular hypertrophy (LVH) and valvular and myocardial calcification has been observed. Associations have been found between PTH and LVH, and between LVH and serum calcium. LV systolic function does not seem to be affected in patients with pHPT, whereas any influence on LV diastolic performance needs further evaluation. The aim of this review is to clarify the connection between pHPT and cardiac disease.
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PMID:Primary hyperparathyroidism and heart disease--a review. 1547 92

Chronic heart failure (CHF) remains an important and increasing public health care problem. It is a complex syndrome affecting many body systems. Body wasting (i.e., cardiac cachexia) has long been recognised as a serious complication of CHF. Cardiac cachexia is associated with poor prognosis, independently of functional disease severity, age, and measures of exercise capacity and cardiac function. Patients with cardiac cachexia suffer from a general loss of fat tissue, lean tissue, and bone tissue. Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but there is increasing evidence that metabolic, neurohormonal and immune abnormalities may play an important role. Cachectic CHF patients show raised plasma levels of epinephrine, norepinephrine, and cortisol, and they show high plasma renin activity and increased plasma aldosterone level. Several studies have also shown that cardiac cachexia is linked to raised plasma levels of tumour necrosis factor alpha and other inflammatory cytokines. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems may cause the development of body wasting.
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PMID:Cardiac cachexia. 1551 2

Adrenal insufficiency is a rare disease, but its prevalence is increasing. The most frequent cause of primary adrenal insufficiency in western countries is autoimmune adrenalitis, whereas secondary adrenal insufficiency is most often caused by pituitary tumours and their treatment (e.g., surgery). Chronic glucocorticoid replacement consists of hydrocortisone 15-25 mg/day in divided doses and dose monitoring is largely based on clinical judgement. Fludrocortisone 0.05-0.2 mg/day is given for substitution in mineralocorticoid deficiency aiming at normotension, normokalaemia and a plasma renin activity in the upper normal range. It has recently been shown that, despite adequate glucocorticoid and mineralocorticoid replacement well being in patients with adrenal insufficiency is still impaired. Several studies have demonstrated that dehydroepiandosterone 25-50 mg/day p.o. may improve mood, fatigue, well-being and, in women, also sexuality, suggesting that dehydroepiandosterone should become part of the standard treatment regime. However, large Phase III trials of dehydroepiandosterone for adrenal insufficiency are still lacking and it has not yet been approved for the treatment of this disease. Patients with adrenal insufficiency are at risk of adrenal crisis, usually precipitated by major stress, such as severe infection or surgery. Early dose adjustments are required to cover the increased glucocorticoid demand in stress. Careful and repeated education of patients and their partners is the best strategy to avoid this life-threatening emergency. Some recent studies suggest that during sepsis some patients with intact adrenal function may develop transient relative adrenal insufficiency and benefit from administration of hydrocortisone plus fludrocortisone. However, the pathophysiology and diagnosis criteria of relative adrenal insufficiency and its treatment remain unsettled issues.
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PMID:Management of adrenal insufficiency in different clinical settings. 1625 72

B-type natriuretic peptide (BNP) is an endogenous cardiac neurohormone, produced in the ventricles in response to pressure and volume elevation. Nesiritide is identical to endogenous BNP and is synthesized using recombinant DNA technology. It is currently used in the treatment of acute decompensated heart failure. In clinical trials, nesiritide has been shown to decrease pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance, as well as increase cardiac index and stroke volume index. Infusions of nesiritide have led to increased diuresis and natriuresis. Patients treated with nesiritide have reported improvements in global clinical status, dyspnea, and fatigue. Therapy with nesiritide has resulted in decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels, as well as reduced ventricular ectopy and ventricular tachycardia. Heart rate variability also improved with nesiritide. Patients with acute coronary syndromes, serious arrhythmia, renal disease, diastolic dysfunction, or vasopressor dependence have been safely managed with nesiritide. Early treatment with nesiritide in the emergency department may lead to decreased length of hospital stay and reduced readmission rates compared to standard care. Outpatient serial infusions of nesiritide in severe heart failure patients on optimal medical therapy may result in improved clinical status, increased ejection fraction, reduced aldosterone and endothelin-1 levels, and decreased hospitalizations. Potential future uses of nesiritide include treatment of acute coronary syndromes, pulmonary hypertension, bronchospasm in chronic lung disease, and as antifibrotic/anti-remodeling therapy or bridge to cardiac transplant. The possibility of subcutaneous injections of nesiritide has been studied in both animals and humans.
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PMID:Nesiritide: past, present, and future. 1633 35


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