Deficiency of aldosterone and cortisol production due to loss of gland function → hypotension (hyponatremic volume contraction), hyperkalemia, metabolic acidosis, skin and mucosal hyperpigmentation (due to ↑ MSH, a byproduct of ACTH production from proopiomelanocortin [POMC]).

- Acute – sudden onset (eg, due to massive hemorrhage). May present with shock in acute adrenal crisis.- Chronic – Addison disease. Due to adrenal atrophy or destruction by disease (autoimmune destruction most common in the Western world; TB most common in the developing world).

- Associated with autoimmune polyglandular syndromes.

- Waterhouse-Friderichsen syndrome – acute 1° adrenal insufficiency due to adrenal hemorrhage associated with septicemia (usually Neisseria meningitidis), DIC, endotoxic shock.