Hyponatremia in Marathon Runners due to Inappropriate Arginine Vasopressin Secretion

Abstract 

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 = <.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.

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.

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