Adrenal Insufficiency: Primary, Secondary and Adrenal

Adrenal insufficiency results from inadequate cortisol production and is classified by the level of HPA axis disruption. Primary adrenal insufficiency (Addison disease) involves destruction of the adrenal cortex itself — autoimmune adrenalitis (most common in developed countries, anti-21-hydroxylase antibodies), infections (TB — most common worldwide, CMV in HIV), hemorrhagic infarction (Waterhouse-Friderichsen syndrome in meningococcemia), or metastatic infiltration. Both glucocorticoid (cortisol) and mineralocorticoid (aldosterone) production are lost, causing hypotension, hyperkalemia, and hyponatremia. Loss of negative feedback on the pituitary increases ACTH and MSH (cleaved from the same POMC precursor), causing hyperpigmentation in skin creases, buccal mucosa, and scars — a hallmark of primary adrenal insufficiency. Secondary adrenal insufficiency results from pituitary ACTH deficiency (pituitary tumors, surgery, Sheehan syndrome) — cortisol is deficient but aldosterone is preserved (regulated primarily by RAAS, not ACTH), so hyperkalemia and hyperpigmentation do NOT occur. Tertiary adrenal insufficiency is the most common form — chronic exogenous glucocorticoid suppression of CRH/ACTH (HPA axis suppression) followed by abrupt cessation. The adrenal glands atrophy and cannot respond to stress. Adrenal crisis is a life-threatening emergency: acute circulatory collapse with hypotension...