Clinical meaning
Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion is characterized by excessive ADH (vasopressin) release independent of normal osmotic or hemodynamic stimuli. ADH is normally produced by the hypothalamus (supraoptic and paraventricular nuclei) and released from the posterior pituitary in response to increased serum osmolality or decreased blood volume. In SIADH, ADH is released inappropriately, causing: insertion of aquaporin-2 channels in the collecting duct → excessive free water reabsorption → dilutional hyponatremia (serum Na+ <135 mEq/L) with inappropriately concentrated urine (urine osmolality >100 mOsm/kg). Critically, SIADH is a EUVOLEMIC hyponatremia — the excess water distributes throughout body compartments, causing only mild volume expansion that triggers compensatory natriuresis (kidney excretes sodium to match the mild volume expansion, further lowering serum sodium). Causes: CNS disorders (stroke, TBI, meningitis, SAH), pulmonary disease (pneumonia, TB, lung cancer — especially small cell), medications (SSRIs, carbamazepine, cyclophosphamide, vincristine, desmopressin, oxytocin), pain, nausea, and ectopic ADH production (small cell lung cancer — most important malignant cause). Diagnosis requires: hyponatremia, low serum osmolality (<275 mOsm/kg), urine osmolality >100 mOsm/kg (inappropriately concentrated), urine sodium >30 mEq/L, EUVOLEMIC status, and normal thyroid/adrenal function (must rule out hypothyroidism and adrenal insufficiency which mimic SIADH).