One is struck with the degree of emaciation; it exceeds that of most of the known wasting diseases. Often 30 percent or more of the body weight will have been lost by the time the patient’s family insists on medical consultation. Bradycardia and hypotension are indicators for hospitalization. A fine lanugo covers the face, body, and limbs. The skin is thin and dry, without its normal elasticity, and the nails are brittle. The dental enamel is eroded. Pubic hair and breast tissue (except for loss of fat) are normal, and, in this respect, anorexia nervosa is unlike hypopituitary cachexia (Simmonds disease). Surprisingly, however, there are no neurologic signs of nutritional deficiency. The patient is alert and cheerfully indifferent to her condition. Any suggestion that she is unattractively thin or seriously depleted is rejected.
Amenorrhea is practically always present and may precede the extreme weight loss. Luteinizing hormone (LH) concentrations are reduced to pubertal or prepubertal levels. Clomiphene citrate fails to stimulate a rise in LH, as it does normally. Administration of gonadotropic-releasing factor raises the LH and follicle-stimulating hormone (FSH) levels, suggesting a hypothalamic disorder. The basal metabolic rate is low; triiodothyronine (T3) and thyroxine (T4) are low, while levels of physiologically inactive 3,3,5-triiodothyronine (reverse T3) are normal or increased. Plasma thyrotropin (thyroid-stimulating hormone [TSH]) and growth hormone levels are normal. Serum cortisol levels are usually normal; excretion of 17-hydroxysteroids is slightly reduced. In sum, there is evidence of hypothalamic–pituitary dysfunction, but this is probably secondary to starvation, as indicated by the study of Scheithauer and colleagues who found no definite changes in the pituitary gland in 12 fatal cases. These endocrine abnormalities, most of which are probably secondary effects of weight loss, are summarized in the review by Becker and colleagues. Brain imaging shows slight to moderate enlargement of the lateral and third ventricles, which return to normal size when the illness subsides.
The etiology of anorexia nervosa is unknown, although there is no lack of hypotheses. Holland and coworkers reported a high concordance in monozygotic twins as compared with dizygotic twins. Earlier signs of hysterical tendencies, obsessional personality traits, and depression are mentioned as being frequent in some series, but not in others. Certain polymorphisms in the serotonin transporter gene, of types different from those that have been tentatively attached to anxiety and to obsessive traits, have also been reported. These findings are difficult to interpret. A functional imaging study has shown activation of the left insula, amygdala, and cingulate when high-calorie drinks were imbibed by anorectic women (Ellison et al), but this conceivably may have reflected anxiety that the authors termed calorie fear rather than a specific biologic feature of the disease.
Reports concerning the percentage of first-degree relatives of anorectic patients with bipolar disease are also inconsistent. An increased prevalence of neurosis or alcoholism has been noted in other members of the family. However, psychiatrists seem to agree that the patient does not have symptoms that conform to any of the major neuroses or psychoses. Certainly loss of appetite, lack of self-esteem and interest in personal appearance, and self-destructive behavior—common features of anorexia nervosa—are also symptoms of depressive illness, yet most of the patients do not look or admit to being dejected. Moreover, endogenous depression affects both sexes. The pathologic fear of becoming fat and the obsession with weight might be interpreted as a phobic or obsessional neurosis.