One of the most provocative observations in contemporary psychiatry has been that apparently healthy individuals may become psychotic when they develop hyperor hypothyroidism or Cushing syndrome, or less often, adrenal insufficiency, or when they receive therapeutic doses of corticosteroids. If these conditions were no more than examples of drug-induced psychosis, they would be interesting enough. The fact is, however, that they differ considerably from the usual toxic deliria or confusional states. The syndrome comprises features that are suggestive of bipolar psychosis or schizophrenia on the one hand and of confusional psychosis on the other. These endocrine psychoses have far-reaching medical significance, for they provide artificial models and a neurologic perspective of psychoses created by the manipulation of metabolic and by exogenous factors. It is appropriate that they are in the last chapter in a book about neurology.
First described in arthritic patients being treated with cortisone, these syndromes are now occurring far less frequently than when corticosteroids were introduced into medical practice. The psychosis usually develops over a period of a few days after the patient has received the hormone for a week or more. The features are extremely variable. Depression and insomnia are the most frequent early symptoms, but some patients become elated, agitated, excited, and talkative, as though under pressure to speak, whereas others are mute; or the prevailing emotional response may be one of anxiety and panic. Thinking may be slightly illogical, tangential, or incoherent. Hallucinations and sensory misinterpretations may appear. However, clouding of the sensorium and disorientation, the hallmarks of deliria and the confusional psychoses, have been less prominent. Nevertheless, the state of awareness is not altogether normal, and at times the patient is frankly bewildered. If administration of the hormone is discontinued as soon as symptoms appear, the psychosis subsides but only gradually over several days to weeks, with complete recovery.
In patients with Cushing disease, mental changes are frequent. In some patients there is a combination of affective disorder and impairment of cognitive function, usually apparent during mental status testing. Also, among athletes taking anabolic steroids, some develop affective and psychotic symptoms—reduced sleep, irritability, aggression, paranoid delusions, auditory hallucinations, and euphoria or depression. Mental changes in Addison disease are frequent but varied. Irritability, confusion, disorientation, and convulsions, with or without symptoms of hypoglycemia, are the main features.
The mechanisms are not well understood. The mechanism of acute steroid psychosis is obscure. From the few available studies it has been learned that the occurrence of the psychosis is not related to the premorbid personality. Although the dosage of adrenocorticotropic hormone (ACTH) or corticosteroid has usually been high, there has been no definite correlation between the dosage and the occurrence, severity, and duration of psychosis. In a study of patients with systemic lupus erythematosus by Chau and Chi, 5 percent of patients became psychotic with steroid treatment, and for an obscure reason, only hypoalbuminemia was found by statistical analysis to be an associated factor. A history of anxiety or of a family history of psychiatric disease had only a marginal predictive value for steroid-induced psychosis. The notion held by many neurologists that dexamethasone is less frequently associated with psychosis than other corticosteroids is unproven. Lithium is often effective in controlling manic symptoms, allowing continuation of the corticosteroid therapy if necessary for the underlying medical condition. The dose is the same as for manic states (see Falk et al).
A great deal has been said about the pervasive effects of abnormal thyroid function on all organs, including the neuromuscular apparatus and central nervous system. These are discussed in Chap. 39 with other acquired metabolic diseases of the nervous system, but mental changes with these endocrinopathies are not nearly as frequent or prominent as for adrenal disorders.