Many states of disordered autonomic function in which static or orthostatic hypotension are features are also associated with a fatigue state. Whether there is in addition a type of central autonomic (hypothalamic) fatigue, aside from the endocrine changes discussed below, is uncertain, but such an entity seems plausible and has been included in models of the illness currently called chronic fatigue syndrome.
A wide variety of medications and other therapeutic agents, particularly when first administered, may induce fatigue. The main offenders in this respect are antihypertensive drugs, especially beta-adrenergic blocking agents, antiepileptic medications, antispasticity drugs, anxiolytics, chemotherapy and radiation therapy and, paradoxically, some antidepressant and antipsychotic drugs. Introduction of these medications in gradually escalating doses may obviate the problem, but just as often, an alternative medicine must be chosen. The administration of beta-interferon for the treatment of multiple sclerosis (and alpha-interferon for other diseases) induces fatigue of varying degree. Surgeons and nurses can testify to fatigue that comes with exposure to anesthetics in inadequately ventilated operating rooms. Similarly, fatigue and headache may result from exposure to carbon monoxide or natural gas in homes with furnaces in disrepair or from leaking gas pipes, but this is also a frequent delusion in anxious, depressed, or demented patients.
The sleep apnea syndrome is an important and often overlooked cause of fatigue and daytime drowsiness. In overweight men who snore loudly and need to nap frequently, testing for sleep apnea is indicated (this subject was taken up in Chap. 18). Correcting the obstructive apnea that underlies this condition leads to a dramatic reduction in fatigue. The same holds for patients who have neuromuscular diseases that affect the diaphragm and other respiratory muscles.
Acute or chronic infection is an important cause of fatigue. Everyone has at some time or other sensed the abrupt onset of exhaustion, a tired ache in the muscles, or an inexplicable listlessness, only to discover later that he was “coming down with the flu.” Chronic infections such as hepatitis, tuberculosis, brucellosis, infectious mononucleosis, HIV, and bacterial endocarditis may not be evident immediately but should be suspected when fatigue is a new symptom and disproportionate to other symptoms such as mood change, nervousness, and anxiety. Whether a chronic form of Lyme disease is responsible for chronic fatigue, as often imputed, is uncertain at best. Often, fatigue begins with an obvious infection (such as influenza, hepatitis, or infectious mononucleosis), but persists for several weeks after the overt manifestations of infection have subsided; it may then be difficult to decide whether the fatigue represents the lingering effects of the infection or is due to psychologic-asthenic symptoms during convalescence. This difficult problem is discussed below. Patients with systemic lupus, Sjögren syndrome, or polymyalgia rheumatica may complain of severe fatigue; in the last of these, fatigue may be the initial and a profound 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 persons with hypothyroidism with or without frank myxedema, lassitude and fatigue are frequent complaints, as are muscle aches and joint pains. In Addison, Sheehan, and Simmonds diseases, fatigue may dominate the clinical picture. Aldosterone deficiency is another established cause of chronic fatigue. 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. Fatigue as a feature of vitamin B12 deficiency, as stated in many textbooks, has not been evident in the cases with mild deficiency that we have observed.