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plain of severe fatigue; in the last of these, fatigue may be the initial symptom Metabolic and endocrine diseases of various types may cause inordinate degrees of lassitude and fatigue Sometimes there is, in addition, a true muscular weakness In Addison and Simmonds diseases, fatigue may dominate the clinical picture Aldosterone de ciency is another established cause of chronic fatigue In persons with hypothyroidism with or without frank myxedema, lassitude and fatigue are frequent complaints, as are muscle aches and joint pains Fatigue may also be present in patients with hyperthyroidism, but it is usually less troublesome than nervousness Uncontrolled diabetes mellitus is accompanied by excessive fatigability, as are hyperparathyroidism, hypogonadism, and Cushing disease Reduced cardiac output and diminished pulmonary reserve are important causes of breathlessness and fatigue, which are brought out by mild exertion Anemia, when severe, is another cause, probably predicated on a similar inadequacy of oxygen supply to tissues Mild grades of anemia are usually asymptomatic, and lassitude is far too often ascribed to it An occult malignant tumor eg, pancreatic carcinoma may announce itself by inordinate fatigue In patients with metastatic carcinoma, leukemia, or multiple myeloma, fatigue is a prominent symptom Uremia is accompanied by fatigue; the associated anemia may play a role Any type of nutritional de ciency may, when severe, cause lassitude; in its early stages, this may be the chief complaint Weight loss and a history of alcoholism and dietary inadequacy provide the clues to the nature of the illness For several weeks or months following myocardial infarction, some patients complain of fatigue out of all proportion to effort In many of these patients, there is accompanying anxiety or depression Much more dif cult to understand is the complaint of fatigue that sometimes precedes myocardial infarction Pregnancy causes fatigue, which may be profound in the later months To some extent the underlying causes, including the work of carrying excess weight and an anemia, are obvious; but if weight gain and hypertension are associated, pre-eclampsia should be suspected Postviral and Chronic Fatigue Syndromes A particularly dif cult problem arises in the patient who complains of severe fatigue for many months or even years after a bout of infectious mononucleosis or some other viral illness This has been appropriately called the postviral fatigue syndrome The majority of patients are women between 20 and 40 years of age, but there are undoubtedly young men with the same illness A few such patients were found to have unusually high titers of antibody to EBV, which suggested a causal relationship and gave rise to terms such as the chronic infectious mononucleosis or chronic EBV syndrome (Strauss et al) However, subsequent studies made it clear that a vast majority of patients with complaints of chronic fatigue have neither a clear-cut history of infectious mononucleosis nor serologic evidence of such an infection (Strauss; Holmes et al) In some of these patients the fatigue state has allegedly been associated with obscure immunologic abnormalities simliar to those attributed (spuriously) to silicone breast implants or minor trauma The currently fashionable designation for these and other abstruse states of persistent fatigue is the chronic fatigue syndrome Some perspective is provided by the recognition that a malady of this precise nature, under many different names, has long pervaded postindustrial western society, as described by Shorter in an informative history of the chronic.

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fatigue syndrome The attribution of fatigure to viral infection and to ill-de ned immune dysfunction are only the latest in a long line of putative explanations At various times, even in our recent memory, colitis and other forms of bowel dysfunction, spinal irritation, hypoglycemia, brucellosis, and chronic candidiasis, multiple chemical sensitivity, or environmental allergies, among others, have been proposed as causes The current criteria for the diagnosis of chronic fatigue syndrome are the presence of persistent and disabling fatigue for at least 6 months, coupled with an arbitrary number (six or eight) of persistent or recurrent somatic and neuropsychologic symptoms including low-grade fever, cervical or axillary lymphadenopathy, myalgias, migrating arthralgias, sore throat, forgetfulness, headaches, dif culties in concentration and thinking, irritability, and sleep disturbances (Holmes et al) A common association is with the similarly obscure entity and painful bromyalgia state, consisting of neck, shoulder, and paraspinal pain and point tenderness (pages 190 and 1281) Despite these complaints, the patient may look surprisingly rested and robust and the neurologic examination is normal The term myalgic encephalomyelitis, which is preferred in Great Britain, captures this association A number of such patients, in our experience, have complained of paresthesias in the feet or hands On close questioning, many of these sensations prove to be odd, particularly numbness in the bones or muscles or uctuating patches of numbness or paresthesias on the chest, face, or nose Bizarre adjectives are sometimes given if the patient is allowed adequate time to describe the symptoms A few of our patients have reported blurred or close to double vision In neither case are there physical ndings to corroborate the sensory experiences Complaints of muscle weakness are also frequent among such patients, but Lloyd and coworkers, who studied their neuromuscular performance and compared them with control subjects, found no difference in maximal isometric strength or endurance in repetitive submaximal exercise and no change in intramuscular acidosis, serum CK levels, or depletion of energy substrates These individuals share with depressed patients a subnormal response to cortical magnetic motor stimulation after exercise (Samii et al), which can be said to match their symptoms of reduced endurance but otherwise is dif cult to interpret In a small number of affected persons, a chronic but usually mild hypotension, elicited mainly with tilttable testing and reversed by mineralocorticoids, has been proposed as a cause of chronic fatigue (Rowe et al) Electromyography and nerve conduction studies are invariably normal, as is the spinal uid, but the electroencephalogram (EEG) may be mildly and nonspeci cally slowed Batteries of psychologic tests have disclosed variable impairments of cognitive function, misinterpreted by advocates of the organic nature of the syndrome as proof of some type of encephalopathy In a large group of patients who were studied 6 months after viral infections, Cope and colleagues found that none of the features of the original illness was predictive of the development of chronic fatigue; however, a previous history of fatigue or psychiatric morbidity and an inde nite diagnosis were often associated with persistent disability In one study of more than 1000 patients who were observed for 6 months following an infective illness, the chronic fatigue syndrome was no more frequent than in the general population (Wessely et al) One thing is clear to the authors: that applying the label of chronic fatigue syndrome in susceptible individuals tends to always perpetuate this state.