Hyponatremia in Marathon Runners due to Inappropriate Arginine Vasopressin Secretion



      Exercise-associated hyponatremia (EAH), as defined by a blood sodium concentration [Na+] less than 135 mmol/L, may lead to hypotonic encephalopathy with fatal cerebral edema. Understanding the pathogenetic role of antidiuresis may lead to improved strategies for prevention and treatment.


      Normonatremic marathon runners were tested pre- and post-race for creatine kinase, interleukin-6, cortisol, prolactin, and arginine vasopressin. Similar testing also was carried out in runners with encephalopathy caused by EAH, including 2 cases with fatal cerebral edema.


      Normonatremic runners (n = 33; 2001) with a mean 3% decrease in body weight showed a 40-fold increase in interleukin-6 (66.6 ± 11.9 pg/mL from 1.6 ± 0.5 pg/mL, P = .001), which was significantly correlated with increases in creatine kinase (r = 0.88, P = <.0001), cortisol (r = 0.70, P = .0003), and prolactin (r = 0.67, P <.007), but not arginine vasopressin (r = 0.44, P = .07). Collapsed runners with EAH (n = 22; 2004) showed a mean blood urea nitrogen less than 15 mg/dL with measurable plasma levels of arginine vasopressin (>0.5 pg/mL) in 43% of cases. Two marathon runners with fatal cerebral edema additionally showed less than maximally dilute urines (>100 mmol/kg/H2O) and urine [Na+] greater than 25 mEq/L.


      Cases of EAH fulfill the essential diagnostic criteria for the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Runners with hypotonic encephalopathy at subsequent races were treated with intravenous hypertonic (3%) saline on the basis of this paradigm, which resulted in rapid clinical improvement without adverse effects. Release of muscle-derived interleukin-6 may play a role in the nonosmotic secretion of arginine vasopressin, thereby linking rhabdomyolysis to the pathogenesis of EAH.


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