The Syndrome of Inappropriate Secretion of Antidiuretic Hormone: Diagnostic and Therapeutic Advances

Abstract

Hyponatremia is the most common electrolyte disorder and its presence predicts poor prognosis. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is among the most frequent causes of hyponatremia and is caused by a variety of disorders and pathomechanisms, mostly related to malignancy, pulmonary, or neurologic disorders. The introduction of small molecule vasopressin receptor-2 (VR2) antagonists, so called vaptans, into clinical medicine for the treatment of SIADH makes a reliable diagnosis of SIADH mandatory. This requires structured assessment of essential and supplemental criteria of SIADH, an approach that is currently frequently neglected in clinical routine. Hypertonic saline remains the gold standard in the initial treatment of symptomatic SIADH with severe neurological deficits. However, correction of hyponatremia needs to be slow (<10-12 mmol/l within the first 24 h, and <18 mmol/l within the first 48 h, respectively) to avoid osmotic myelinolysis. Fluid restriction and demeclocyclin have been the most widely used treatments for chronic hyponatremia in SIADH. However, fluid restriction suffers from poor long-term acceptance and demeclocyclin lacks broad availability and has been associated with safety concerns. In controlled clinical trials vaptans have been shown to be efficacious both during short-term and long-term administration (up to 12 months) for mild to moderate SIADH with an acceptable safety profile. However, clinical experience with vaptans in SIADH outside of carefully monitored clinical trials remains still rather limited. Thus, careful postmarketing surveillance will be crucial to fully appreciate the risks and benefits of this new class of drugs in SIADH.