Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH causes an unrelenting increase in solute-free water being returned by the tubules of the kidney to the venous circulation. The causes of SIADH are grouped into six categories: 1) central nervous system diseases that directly stimulate the hypothalamus, the site of control of ADH secretion; 2) various cancers that synthesize and secrete ectopic ADH; 3) various lung diseases; 4) numerous drugs that chemically stimulate the hypothalamus; 5) inherited mutations; and 6) miscellaneous largely transient conditions. ADH is derived from a preprohormone precursor that is synthesized in cells in the hypothalamus and stored in vesicles in the posterior pituitary. Appropriate ADH secretion is regulated by osmoreceptors on the hypothalamic cells that synthesize and store ADH: plasma hypertonicity activates these receptors, ADH is released into the blood stream, the kidney increases solute-free water return to the circulation, and the hypertonicity is alleviated. Inappropriate (increased) ADH secretion causes an unrelenting increase in solute-free water ("free water") absorption by the kidneys, with two consequences. First, in the extracellular fluid (ECF) space, there is a dilution of blood solutes, causing hypoosmolality, including a low sodium concentration - hyponatremia. Then virtually simultaneously, in the intracellular space, cells swell, i.e. intracellular volume increases. Swelling of brain cells causes various neurological abnormalities which in severe or acute cases can result in convulsions, coma, and death. Potential treatments of SIADH include restriction of fluid intake, correction of an identifiable reversible underlying cause, and/or medication which promotes solute-free water excretion by the kidney. The presence of cerebral edema may necessitate intravenous isotonic or hypertonic saline administration. SIADH was originally described in 1957 in two people with small-cell carcinoma of the lung. Signs and symptoms Gastro-intestinal Anorexia Nausea Musculoskeletal Muscle aches Generalized muscle weakness Neuro-muscular Myoclonus Decreased reflexes Ataxia Pathological reflexes Tremor Asterixis Respiratory Cheyne-Stokes respiration Neurological Dysarthria Lethargy Confusion Delirium Seizures Coma (from brain swelling) Death Causes Causes of SIADH include conditions that dysregulate ADH secretion in the central nervous system, tumors that secrete ADH, drugs that increase ADH secretion, and many others. A list of common causes is below: Pathophysiology Normally there are homeostatic processes in the body which maintain the concentration of body solutes within a narrow range, both inside and outside cells. The process occurs as follows: