The Syndrome of Inappropriate Antidiuresis

Abstract The syndrome of inappropriate antidiuresis (SIAD)–the most frequent cause of hypotonic hyponatremia–is mediated by nonosmotic release of arginine vasopressin (AVP), which promotes water retention by activating renal vasopressin type 2 (V2) receptors. There are numerous causes of SIAD, including malignancy, pulmonary and central nervous system diseases and medications. Rare activating mutations of the V2 receptor can also cause SIAD Determination of the etiology of SIAD is important because removal of the stimulus for inappropriate AVP secretion offers the most effective therapy. Treatment of SIAD is guided by symptoms and their severity as well as the level of plasma sodium. In the absence of severe symptoms which require urgent intervention, many clinicians focus on fluid restriction as a first-line treatment. Second-line therapeutic options include loop diuretics and salt tablets, urea, and V2 receptor antagonists.