To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function. (N Engl J Med 1986; 314:1335–42.), ANOREXIA nervosa is thought to be a psychiatric syndrome characterized by a striking increase in physical activity and a marked diminution of food intake in the obsessive pursuit of thinness.1 2 3 The course of this disorder can be erratic, with periods of extreme weight loss alternating with periods in which weight is maintained at relatively normal levels. Almost invariably, the underweight phase of anorexia nervosa is associated with clear-cut abnormalities in neuroendocrine function, which usually resolve weeks to months after correction of the weight loss. The best characterized of these abnormalities include hypothalamic hypogonadism,4 5 6 abnormal regulation of plasma and cerebrospinal fluid.
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