Comment| Volume 27, ISSUE 9, P937-952, May 01, 1990

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Hypercortisolism and its possible neural bases

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      As is clear from the pages of this journal, biological psychiatrists remain fascinated by the phenomenon of dexamethasone (DEX) resistance and the hypercorticosolism of various neuropsychiatric disorders. The mere existence of the endocrine abnormalities attests to the biological reality of these disorders. Furthermore, progress continues in using the occurence of these endocrine defects as both diagnostic and prognostic markers of disease subtypes.
      Progress has also been made in understanding the mechanisms underlying the endocrine defects. The adrenocortical axis is vastly complex, involving multiple hypothalamic-releasing factors under CNS control, shifting pituitary and adrenal sensitivies to hormonal signals, and feedback regulation at all three levels. What defects within this system produce DEX resistance and hypercortisolism? In this paper, we review data suggesting that the endocrine problems is, at least in part, neural in nature. Drawing upon a rodent literature, we will also suggest some models by which this can occur. The hypercorticolism found in cases of affective disorders, anorexia nervosa, Alzheimer's disease, among the very aged or the chronically stressed, is not a uniform phenomenon. Basal cortisol concentrations can be elevated in all or part of the circadian cycle. Resistance to glucocorticoid (GC) feedback inhibition (as typically demonstrated by DEX resistance) can occur; the resistance can be complete, or occur as early escape from DEX suppression. Finally, elevated basal cortisol concentrations and DEX resistance can occur independently of each other. Until the end of this review, we will conveniently refer to these variants of adrenocortical hyperactivity as “hypercortisolism”. In addition, rather than using the term “hypercortisolism” for the rat, we will use “hyperadrenocorticism” (as they secrete corticosterone, rather than cortisol).
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