Syndrome of Inappropriate Antidiuresis: From Pathophysiology to Management.

Hyponatremia is the most common electrolyte disorder, affecting more than 15% of patients in hospital. The syndrome of inappropriate anti-diuresis (SIAD) is the most frequent cause of hypotonic hyponatremia, mediated by non-osmotic release of arginine vasopressin (AVP, previously known as anti-diuretic hormone (ADH)) which acts on the renal V2 receptors to promote water retention. There are a variety of underlying causes of SIAD, including malignancy, pulmonary pathology and central nervous system pathology. In clinical practice, the etiology of hyponatremia is frequently multifactorial and the management approach may need to evolve during treatment of a single episode. It is therefore important to regularly reassess clinical status and biochemistry, whilst remaining alert to potential underlying etiological factors that may become more apparent during the course of treatment. In the absence of severe symptoms requiring urgent intervention, fluid restriction is widely endorsed as first line treatment for SIAD in current guidelines, but there is significant controversy regarding second line therapy in instances where fluid restriction is unsuccessful, which occurs in around half of cases. We review the epidemiology, pathophysiology and differential diagnosis of SIAD, and summarise recent evidence for therapeutic options beyond fluid restriction, with a focus on tolvaptan, urea and sodium-glucose co-transporter 2 inhibitors (SGLT2i).