Dysfunction of the adrenal cortex: an exploration of molecular mechanisms

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Abstract
Adrenal dysfunction caused by acute damage to the adrenal cortex may result in adrenal insufficiency, which may have critical consequences in severely ill patients. There is also a form of chronic dysfunction, occurring in all individuals over the lifespan, which results in a loss of adrenal androgen secretion. Here it is hypothesized that these acute and chronic changes are related. Injury to the adrenal cortex ranges from severe life-threatening hemorrhage to small infarcts/limited apoptosis. A common pathway of damage may involve injury of the microvasculature. Cell death may occur via necrosis of a segment of tissue or via a series of cellular events involving DNA damage, p53 and p21. Chronic changes may be the result of multiple small-scale acute changes that occur from time to time. The permanency of the changes is accounted for by an imperfect repair of the acute damage, and therefore over long periods the damage is cumulative. Whereas acute dysfunction of the adrenal cortex is an important clinical problem in very ill patients, the long-term milder dysfunction discussed here is important because it affects all individuals to varying extents during aging.