Anorexia Nervosa is an increasingly common disorder among adolescent girls with a reported mortality rate as high as 5-20%. Most therapeutic invterventions have centered on psychiatric modalities. This study proposes a medical intervention. Patients with anorexia nervosa may have a resistance to glucocorticoid (GC) action. Sustained elevations of GC in these underweight patients are maintained without obvious manifestations of hypercortisolemia (eg. Cushingoid habitus, hypertension). The resistance to glucocorticoid could either be generalized or present in the brain. The involvement of a GC antagonist can be postulated that is either made in or acts on the brain. Candidates include neurosteroids (eg. pregnenolone, progesterone) or unknown substances. Disease onset, perhaps triggered by psychiatric events, may result in elevation of these GC antagonists. In this setting of GC resistance, the hippocampus and hypothalamus may sense a lower concentration of GC, and consequently compensate by increasing corticotropin-releasing hormone (CRH) secretion. The HPA axis may thus be stimulated to produce more GC. Higher output of CRH then results, activating pituitary corticotrophs to continue stimulation of the HPA axis, as well receptors in other brain regions. Anorexia, hyperactivity, and decreased sexual function result. By suppressing an overactive HPA axis, the hoped for result is to lower CRH levels. If anorexia nervosa is due to GC resistance and a compensatory HPA axis response, it should be possible to reverse HPA axis overactivation by suppression with exogenous GC. During administration of exogenous GC, it should be possible to determine whether anorexia nervosa patients have GC resistance. Patients will receive dexamethasone, a pure GC agonist, approximately 5 times higher than a daily physiological replacement dose. A correlation between HPA suppression and anorectic behavior will be made.
The aim of the study is to understand regulation of this endocrine system and the underlying pathogenesis of anorexia nervosa.
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