Hyponatremia in Marathon Runners due to Inappropriate Arginine Vasopressin Secretion

  • Siegel A
  • Verbalis J
  • Clement S
 et al. 
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Purpose: 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. Methods: 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. Results: 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 = 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. Conclusions: 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. © 2007 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Arginine vasopressin
  • Exercise-associated hyponatremia
  • Hypertonic (3%) saline
  • Interleukin-6
  • Rhabdomyolysis
  • Syndrome of inappropriate antidiuretic hormone secretion

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  • Joseph G. Verbalis

  • Stephen Clement

  • Jack H. Mendelson

  • Nancy K. Mello

  • Marvin Adner

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