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[9] hypothesized that the nature of the underlying disease rather than hyponatremia itself was responsible for mortality. However, another plausible explanation is that hyponatremia may contribute to organ dysfunction and, therefore, indirectly contribute to mortality (Figure?1) [8]. Figure?1: Possible relationships between selleck chemical hyponatremia and mortality [8]. The figure?illustrates possible scenarios to explain the relationship between hyponatremia and mortality. In one scenario, hyponatremia and mortality are both caused by severe underlying ... Support for this latter hypothesis is increasing with emerging data revealing the presence of significant morbidity in patients with hyponatremia, even in those traditionally STI571 chemical structure presumed to be asymptomatic. In the past, treatment for the condition was only considered in patients with severe hyponatremia (serum [Na+] UNC2881 hormone (SIADH) [13], a condition first described by Bartter and Schwartz [14]. Hyponatremia secondary to SIADH is the focus of our patient case reviews in this supplement. In a healthy body, vasopressin [also known as arginine vasopressin (AVP) or antidiuretic hormone (ADH)] acts in response to an increase in serum osmolality to retain water at the kidney nephron. As its name implies, patients with SIADH have unregulated secretion of vasopressin despite hypotonicity of the serum. Consequently, water intake combined with a high concentration of vasopressin leads to antidiuresis eventually resulting in hyponatremia. Research over the past 40 years has uncovered a long list of potential causes of SIADH; these causes can be categorized as related to malignant diseases, pulmonary diseases and disorders of the central nervous system, as well as idiopathic forms [15]. Criteria now exist to definitively diagnose the condition, with the clinical assessment of the patient's fluid status forming a key part (Table?1). Table?1. Essential and supporting diagnostic criteria for hyponatremia secondary to SIADH [15] The management of SIADH Owing to a relative lack of randomized controlled trials, the treatment of SIADH is largely based on expert opinion and uses agents commonly approved for indications other than for hyponatremia [16].