Syndrome of Inappropriate Antidiuresis: From Pathophysiology to Management

Abstract

Hyponatremia is the most common electrolyte disorder, affecting more than 15% of patients in the hospital. Syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hypotonic hyponatremia, mediated by nonosmotic release of arginine vasopressin (AVP, previously known as antidiuretic hormone), 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, while 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 (FR) is widely endorsed as the first-line treatment for SIAD in current guidelines, but there is considerable controversy regarding second-line therapy in instances where FR is unsuccessful, which occurs in around half of cases. We review the epidemiology, pathophysiology, and differential diagnosis of SIAD, and summarize recent evidence for therapeutic options beyond FR, with a focus on tolvaptan, urea, and sodium-glucose cotransporter 2 inhibitors. Graphical Abstract Syndrome of inappropriate antidiuresis: from pathophysiology to management In-depth review H20 Chronic SIAD Hyponatremia: Osmolytes Fluid restriction <1L ! Acute severe symptoms? e.g. vomit, seizure, coma Refractory to fluid restriction? (4% >15% below hospital 130 patients mmol/L) overHypertonic~15 100ml minutes. 3%salineCan NaCl repeatbolus:x2 to achieve 4-6 mmol/L rise Second line SIAD therapy SIAD most common cause Na+ correction: Tolvaptan Urea SGLT2i Salt furosemide tablets Target: 4-8 mmol/L/day (4-6 mmol/L/24 hrs if risk factors for ODS: pNa < 105, alcohol, malnutrition) Limit: 10 mmol/L/day Na+ improving at target rate? (6-8 mmol/L/24 hrs if ODS risk factors) AVP Neurophysin Copeptin Too fast? Yes Too slow? Acute risk: cerebral edema AVP Principal cell H20 V2 receptor Continue until Na+ normalized Aquaporin Aquaporin Relowering of serum Na+: • Increase dose vesicle • Hypotonic fluid • Reassess diagnosis (5% dextrose IV) • Alternative second Chroniccognition,risks: falls,mortalityfracture, SIAD:resorptionincreaseddue torenalAVP excesswater • +/– post-tolvaptan) DDAVP (except line therapy © 2023 Endocrine Society