Graves' disease (clinical aspects of Graves' disease)]

Graves' disease (GD) is an autoimmune thyroid disease. In addition to the etiology of hyperthyroidism, TSH receptor antibodies play an important role in the pathogenesis of pretibial myxedema, ophthalmopathy, and neonatal GD. The previous epidemiological surveys have revealed that 0.08-0.6% of the population were affected by GD in Japan. Clinical signs and symptoms as well as laboratory abnormalities are described with emphasis on elevated serum VEGF and G-CSF levels in untreated GD patients. It should be noted that elderly patients may not have typical symptoms of hyperthyroidism, but cardiac symptoms and weight loss usually predominate. Abnormal laboratory findings may help to make a diagnosis in asymptomatic patients. Patients with ophthalmopathy may have antibodies to 64 kD/55 kD external orbital muscle proteins.     

Autoimmunity and Graves' disease

Current treatment options for Graves' hyperthyroidism and the related ophthalmopathy (GO) are not uniformly effective and carry with them potentially serious side effects. As a result, efforts have been focused on the development of novel therapies. Progress has been made, particularly in the production of thyroid-stimulating hormone receptor (TSHR) antagonists, as either monoclonal blocking antibodies or small-molecule ligands. In addition, rituximab (RTX) is the first targeted biological therapy to be studied as treatment for these conditions.     

Graves' disease and bone metabolism

Thyroid hormone stimulates osteoclastic bone resorption, through increased expression of receptor activator of nuclear factor kappa B ligand (RANKL) in osteoblasts as well as via non-RANKL-mediated pathway. Therefore, in hyperthyroid patients with Graves' disease, bone resorption (urinary excretion of calcium, phosphate, deoxypyridinoline, N-terminal telopeptide of collagen type I) is increased. Due to accelerated bone remodeling, bone formation is also increased. However, the amount of bone formation is less than that of bone resorption, leading to a gradual decrease in bone mineral density (BMD). In young patients, the decreased BMD is reversible, but not in post-menopausal women. Therefore, in these patients with rapid bone looser, bisphosphonates may be beneficial treatment for prevention of osteoporosis and will prevent bone fractures in senile period.     

The ophthalmopathy of Graves' disease

Fortunately, most patients with thyroid-related eye disease have mild ocular involvement that spontaneously involutes. Less than 5% of patients with hyperthyroidism will develop sufficiently severe ocular abnormalities that will require surgical intervention. Most patients with thyroid eye findings should be symptomatically managed. Some will require use of either topical drops or oral steroids to alleviate their eye problems. In approximately one half of those patients who present acutely with severe thyroid orbital finding, nonsurgical therapies will be sufficient to control their eye disease. In the other half, eventually multiple surgical procedures may be required, and as discussed previously, the timing and sequence of those procedures are crucial to achieve optimal results.     

Extrathyroidal complications of Graves' disease

Ophthalmopathy, pretibial myxoedema and acropachy are progressivelyless common features of Graves' disease with unknown but probablyrelated aetiologies (Table 1). Treatment for affected eyes andskin is unsatisfactory and will only improve when we understandthe pathogenesis of these complications and their arcane relationshipwith thyroid autoimmunity. This brief review will highlightrecent research which suggests that fibroblast activation iscritical to the appearance of ophthalmopathy and dermopathy;more general overviews can be found elsewhere.^1,2     

Surgical treatment of Graves' disease]

Surgery has a definite role in the management of patients with Graves' disease, although it may be followed by perioperative complications and postoperative thyroid dysfunction. Since alternative treatments such as antithyroid drugs or radioiodine are also available, the decision making in the management should be based on clear assessment of advantages and limitations of each strategy by both patients and physicians. As clinicians caring for patients, we have to make efforts to obtain valid and reliable evidence regarding clinical outcomes of the treatment options so that the information can be used for the decisions in daily medical practices where patients' values and preferences are also important determinants.     

Eye signs of Graves' disease.

Graves' disease can affect the eyes and orbits in many ways, some seemingly trivial, others obviously devastating to vision. Because of the relative simplicity of diagnosing Graves' disease in the majority of cases, and now with the addition of B-scan ultrasonography, much expense and needless risk is avoidable in most patients with ophthalmopathic Graves' disease. Those patients whose diagnosis cannot be confirmed by noninvasive techniques may not have Graves' disease and deserve more in-depth study.     

Immunological effects of Graves' disease therapy

Graves' disease is caused by thyroid stimulating antibodies and is accompanied by other autoimmune phenomena predisposing ultimately towards hypothyroidism. Antithyroid drugs directly alter the natural history of the condition, causing a remission in 50% of cases; part of this is likely to be due to their immunomodulatory effect. Surgery and radioiodine treatment are also accompanied by immunological changes which may affect outcome. In particular, some cases of hypothyroidism may be the result of a hastening of the natural progression to destructive thyroiditis.     

Graves' disease. Manifestations and therapeutic options

Graves' disease is the most common cause of hyperthyroidism. Clinical features include thyroid enlargement, eye signs, tachycardia, heat intolerance, emotional lability, weight loss, and hyperkinesis. Three modes of therapy are available. The preferences of the patient and physician are usually prime considerations in devising the therapeutic plan. Radioactive iodine is the most frequently used and safest method of treatment for adults. Antithyroid drugs are preferred for children and pregnant women. Surgery is usually reserved for patients in whom the other forms of treatment are not acceptable. Considerable patient education during the decision-making process enhances the success of the therapeutic plan.     

Approach to the diagnosis and management of mild bleeding disorders

Summary.  Symptoms suggestive of the presence of a mild bleeding tendency are commonplace. Whilst the majority with such symptoms are healthy, it is important to identify those with bleeding disorders in order to manage symptoms, to minimize risk from invasive procedures and to avoid unnecessary exposure to blood products. Thorough clinical assessment remains the cornerstone of the diagnostic strategy for mild bleeding disorders, although the sensitivity and specificity of the clinical history and examination are limited. When clinical suspicion is aroused the use of a staged protocol of laboratory investigations is appropriate, but the limitations of currently available tests of primary hemostasis and blood coagulation must be recognized if diagnostic errors are to be avoided. Whilst there is considerable current interest in global assays of hemostasis and coagulation, none has yet been demonstrated conclusively to be more effective than the more standard approach. Iatrogenic bleeding has increasing prominence in clinical practise. The expanding use of anticoagulants and platelet inhibitor drugs has resulted in an increased proportion of the population being at risk of abnormal bleeding. Knowledge of the levels of risk associated with particular drugs and combinations, and the advantages and hazards of interruption of drug use for planned interventional procedures, are essential in order to reduce the incidence of iatrogenic bleeding. Prevention and treatment of hemorrhage in subjects with mild bleeding disorders includes the application of general measures, including attention to surgical technique, measures specific to the precise diagnosis, and less specific treatments that enhance hemostasis and coagulation or inhibit fibrinolysis. The last of these includes the widely prescribed drugs desmopressin, aprotinin, epsilon aminocaproic acid and tranexamic acid. Data are now available on their efficacy and safety in a range of clinical situations.     

Acute exacerbations of chronic obstructive pulmonary disease

This article discusses the definition, pathophysiology, cause, clinical presentation, laboratory work-up, and treatment of chronic obstructive pulmonary disease (COPD) exacerbation. The focus is on the presentation of acute exacerbations of COPD in the emergency department and the available evidence for testing and treatment.     

Managing exacerbations of chronic obstructive pulmonary disease

The worldwide incidence of chronic obstructive pulmonary disease (COPD) is increasing and, in parallel, so is the social and economic burden. Mortality data underestimate COPD as a cause of death because the disease is more likely to be cited as a contributory rather than as an underlying cause of death, or may not be cited at all. By 2020, COPD is expected to be the third most common cause of death worldwide yet it receives less funding, publicity and fewer resources than is deemed necessary. The major burden of COPD falls on the patient and carer, and it is difficult to quantify. The quality of life of patients is evident and depends on the severity of their disease and their ability to adapt physically, socially and emotionally to the resulting disability. COPD leads to 30000 deaths per year in the UK. It is a considerable load to the NHS, particularly in the winter months when exacerbations occur most commonly; it results in 13% of all acute medical admissions.