Adrenal Insufficiency, Cushing Syndrome, and Hyperaldosteronism

The adrenal cortex produces three classes of hormones in three zones: zona glomerulosa produces mineralocorticoids (aldosterone, regulated by RAAS and serum potassium), zona fasciculata produces glucocorticoids (cortisol, regulated by ACTH from the anterior pituitary via the HPA axis), and zona reticularis produces androgens (DHEA, androstenedione). Adrenal insufficiency (Addison disease when primary) results from destruction of the adrenal cortex by autoimmune adrenalitis (80% in developed countries), infections (TB, fungal, HIV-related), hemorrhage (Waterhouse-Friderichsen syndrome from meningococcemia), or bilateral adrenalectomy. Loss of cortisol removes negative feedback on the pituitary, causing elevated ACTH, which stimulates melanocyte-stimulating hormone (MSH) production (same precursor molecule POMC), causing hyperpigmentation. Loss of aldosterone causes sodium wasting, potassium retention, and hypovolemia. Cushing syndrome results from chronic glucocorticoid excess—most commonly iatrogenic (exogenous corticosteroid therapy), followed by Cushing disease (ACTH-secreting pituitary adenoma), ectopic ACTH production (small cell lung cancer), or adrenal adenoma/carcinoma. Cortisol excess causes: protein catabolism (muscle wasting, thin skin, striae), glucose intolerance (gluconeogenesis), fat redistribution (central obesity, moon face, buffalo hump), sodium retention with hypokalemia, immunosuppression, and osteoporosis. Hyperaldosteronism (Conn syndrome when primary from adrenal adenoma) causes excessive sodium retention,...