Clinical meaning
The adrenal cortex produces cortisol (zona fasciculata), aldosterone (zona glomerulosa), and androgens (zona reticularis) under regulation by the hypothalamic-pituitary-adrenal (HPA) axis. Cushing syndrome results from chronic cortisol excess, most commonly from exogenous glucocorticoid administration (iatrogenic), ACTH-secreting pituitary adenoma (Cushing disease, 70% of endogenous cases), ectopic ACTH production (small cell lung cancer), or adrenal adenoma/carcinoma. Excess cortisol causes proteolysis (muscle wasting, thin skin, striae), gluconeogenesis (hyperglycemia, insulin resistance), lipogenesis (central obesity, moon facies, buffalo hump), immunosuppression, and osteoporosis. Addison disease (primary adrenal insufficiency) results from autoimmune destruction of the adrenal cortex (80% of cases in developed countries), causing deficiency of cortisol, aldosterone, and androgens. Loss of cortisol negative feedback leads to elevated ACTH and melanocyte-stimulating hormone (MSH), producing characteristic hyperpigmentation. Adrenal crisis is a life-threatening emergency from acute cortisol deficiency precipitated by stress, illness, or abrupt glucocorticoid withdrawal.