Clinical meaning
Addison disease is primary adrenal insufficiency resulting from destruction or dysfunction of the adrenal cortex, leading to deficient production of cortisol (glucocorticoid), aldosterone (mineralocorticoid), and adrenal androgens. The adrenal cortex normally produces these hormones under regulation by the hypothalamic-pituitary-adrenal (HPA) axis, with cortisol secretion driven by ACTH from the anterior pituitary. In Addison disease, at least 90% of the adrenal cortex must be destroyed before clinical insufficiency becomes apparent, reflecting the substantial functional reserve of these glands. The most common cause in developed countries is autoimmune adrenalitis (80-90%), where T-cell-mediated destruction targets adrenocortical cells. Autoantibodies against 21-hydroxylase are present in most cases. It may occur in isolation or as part of autoimmune polyendocrine syndromes (APS type 1 or type 2, associated with thyroid disease, type 1 diabetes, pernicious anemia, vitiligo). Other causes include infectious destruction (tuberculosis is the leading cause worldwide, fungal infections such as histoplasmosis, CMV in AIDS), bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome in meningococcal sepsis, anticoagulant therapy), metastatic disease (lung, breast, melanoma), infiltrative diseases (sarcoidosis, amyloidosis, hemochromatosis), and bilateral adrenalectomy. Cortisol deficiency causes profound metabolic derangements. Cortisol is...