Pathophysiology
Clinical meaning
The clinician manages adrenal disorders through understanding of the hypothalamic-pituitary-adrenal (HPA) axis and adrenal cortical zones. The adrenal cortex produces three classes of steroid hormones organized by zona: zona glomerulosa (aldosterone -- mineralocorticoid, regulated by RAAS and potassium levels), zona fasciculata (cortisol -- glucocorticoid, regulated by ACTH via CRH from the hypothalamus), and zona reticularis (DHEA and androstenedione -- adrenal androgens). Primary adrenal insufficiency (Addison disease) involves destruction of the adrenal cortex (autoimmune in 80-90% of cases in developed countries, tuberculosis globally), causing deficiency of all three hormone classes -- cortisol, aldosterone, and androgens. Elevated ACTH from loss of negative feedback causes hyperpigmentation. Secondary adrenal insufficiency results from ACTH deficiency (pituitary disease or, most commonly, chronic exogenous glucocorticoid suppression of the HPA axis). Diagnostic workup: early morning cortisol (less than 83 nmol/L strongly suggests AI, greater than 500 nmol/L excludes it), ACTH stimulation test (cosyntropin 250 mcg IV/IM with cortisol at 0 and 60 minutes -- cortisol less than 500 nmol/L at 60 minutes confirms AI), simultaneous ACTH level (elevated in primary, low/normal in secondary). Treatment: hydrocortisone 15-25 mg/day in...