Exercise-associated hyponatremia: role of cytokines

Am J Med. 2006 Jul;119(7 Suppl 1):S74-8. doi: 10.1016/j.amjmed.2006.05.012.


Exercise-associated hyponatremia (EAH) has emerged in recent years as a life-threatening complication of endurance sports that may lead to fatal cerebral and pulmonary edema. Defined as a serum sodium concentration <135 mEq/L (1 mEq/L = 1 mmol/L), symptomatic EAH is a dilutional hyponatremia with abnormal fluid retention mediated by decreased urine production, which is a variant of the syndrome of inappropriate antidiuretic hormone secretion. Strategies for prevention and treatment must take into account the pathophysiology underlying this dominant clinical paradigm. Beyond educating runners to drink moderately, monitoring changes in body weight during endurance sports may facilitate the early detection of positive fluid balance characteristic of symptomatic cases. Rapid diagnosis by point-of-care testing indicates the need for fluid restriction in mild cases and emergent treatment with hypertonic (3%) NaCl to reverse acute hypotonic encephalopathy. The efficacy of arginine vasopressin V(2) receptor antagonists warrants study as an alternative treatment to loop diuretics for volume overload in these patients. Nonosmotic stimulation of arginine vasopressin secretion may be mediated in part by enhanced release of muscle-derived interleukin-6 during glycogen depletion, linking exertional rhabdomyolysis to the pathogenesis of EAH.

Publication types

  • Review

MeSH terms

  • Arginine Vasopressin / metabolism
  • Brain Edema / etiology
  • Emergency Treatment / methods*
  • Exercise*
  • Humans
  • Hyponatremia / complications
  • Hyponatremia / diagnosis
  • Hyponatremia / etiology*
  • Hyponatremia / metabolism
  • Hyponatremia / prevention & control
  • Hyponatremia / therapy*
  • Infusions, Intravenous
  • Interleukin-6 / metabolism*
  • Muscle, Skeletal / metabolism
  • Physical Endurance
  • Pulmonary Edema / etiology
  • Rhabdomyolysis / etiology
  • Rhabdomyolysis / metabolism
  • Risk Assessment
  • Saline Solution, Hypertonic / administration & dosage*


  • Interleukin-6
  • Saline Solution, Hypertonic
  • Arginine Vasopressin