Adrenal Disorders: Cortisol Excess

Adrenal pathophysiology encompasses both hypo- and hyperfunctional states affecting each cortical zone and the medulla. Cushing syndrome (cortisol excess) is classified by etiology: ACTH-dependent (Cushing disease from pituitary corticotroph adenoma -- 70% of endogenous cases; ectopic ACTH from small cell lung cancer, carcinoid tumors) versus ACTH-independent (adrenal adenoma, adrenal carcinoma, bilateral macronodular hyperplasia, exogenous glucocorticoid administration -- the most common cause overall). Chronic cortisol excess causes: central obesity (visceral fat accumulation from cortisol-mediated lipogenesis), proximal muscle wasting and weakness (catabolic protein effect), thin skin with easy bruising and striae (impaired collagen synthesis), hyperglycemia (gluconeogenesis stimulation and insulin resistance), hypertension (cortisol activation of mineralocorticoid receptors when 11-beta-hydroxysteroid dehydrogenase type 2 is overwhelmed), osteoporosis (inhibition of osteoblast function and calcium absorption), immunosuppression, and psychiatric disturbances (depression, psychosis). Diagnostic approach: confirm hypercortisolism with two of three screening tests (24-hour urine free cortisol greater than 3x upper limit, late-night salivary cortisol elevated on two occasions, overnight 1-mg dexamethasone suppression test with cortisol greater than 1.8 µg/dL at 8 AM), then determine etiology (ACTH level, high-dose dexamethasone suppression test, inferior petrosal sinus sampling for ACTH-dependent...