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Hormonal Imbalance Triggers Water Intoxication in Marathoners

Belmont, MA - Runners who consume either too much water or sports drinks during a marathon can develop a life-threatening condition called exercise-associated hyponatremia (EAH). Beyond drinking, however, researchers at Harvard-affiliated McLean Hospital report in the May 2007 issue ( abstract) of the American Journal of Medicine that this complication during endurance exercise is also the result of a hormonal stress response, which decreases urine formation and prevents the excretion of excess water.

"This is a major paradigm shift for those who think that EAH is due primarily to salt loss or over-consumption of fluids," said Arthur J. Siegel, MD, chief of the department of Internal Medicine at McLean Hospital. "It' s also an inside job. Avid drinking may be a precondition but dysregulation of the anti-diuretic hormone or arginine vasopressin (AVP), which governs water balance, emerges as the root cause."

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McLean Hospital Researcher Calls for New Preventative and Therapeutic Measures

FOR IMMEDIATE RELEASE:
April 30, 2007

CONTACT:
Public Affairs
Adriana Bobinchock
617.855.2110

Secretion of AVP governs water balance and is normally suppressed when an excess is present in body fluids. "Failure of appropriate suppression prevents excretion of excess water, which results in the rapid fall of blood sodium levels," Siegel said. "Continued ingestion of dilute fluids, including sports drinks, leads to potentially fatal acute cerebral edema under such circumstances."

Siegel and colleagues from across Partners HeathCare came to this understanding after testing blood samples from asymptomatic and collapsed runners at the 2001, 2002, 2003 and 2004 Boston Marathons, including investigation of two fatal cases in 2002 with permission of their families. The findings confirmed inappropriate secretion of AVP as the proximate cause, meeting criteria for a condition first described in the American Journal of Medicine in 1967. This connection pointed to using hypertonic solutions, such as three-percent saline, as a treatment for life threatening cases of EAH, as previously validated for this syndrome.

Once EAH is diagnosed in a runner, concentrated bouillon can be given orally for those who can drink or three-percent saline can be given intravenously for those experiencing seizures or coma. In collaboration with colleagues at Georgetown University Hospital in Washington, D.C., positive clinical results were reported at recent Boston and Marine Corps Marathons, including a protocol for initiating treatment in the medical tent at the former race."

We are on a mission to promote preventive measures based on these findings as well as this novel approach to treatment when prevention fails," Siegel said, noting that many physicians in both sports and academic medicine remain skeptical."The message especially for slower runners, such as charity fund raisers, is awareness that over-hydration is more dangerous than dehydration," said Siegel."Such participants may need to decrease their drinking rate commensurate with their race pace."

Siegel also encourages runners to monitor changes in body weight to monitor fluid status during training as advised in new American College of Sports Medicine guidelines. Scales for this purpose have been available in Red Cross stations at the recent Boston race to assist in early diagnosis before progression to collapse."Runners who gain weight are over-hydrating and need to restrict intake of both water and sports drinks," he said."Symptomatic runners are evaluated with blood tests, as early symptoms of EAH may be similar to those during deydration. This strategy can differentiate these opposite disorders of hydration for triage to condition-specific treatment protocols."

The cause of AVP dysregulaton during prolonged exercise was also addressed in the article. The cytokine interleukin (IL)-6 is released from skeletal muscle after"hitting the wall," which triggers secretion of stress-response hormones, including cortisol, prolactin and AVP, under conditions where the latter should normally be suppressed. "We were confronted with the conundrum of how a runner could succumb to fatal water intoxication during a marathon,'' he stated. "Identifying the root cause pointed us to novel strategies for prevention and treatment."

The current article is dedicated in part to the legacy of Cynthia Lucero, PhD, who wrote her thesis on marathon running to relieve stress in patients and families coping with cancer before she died as a result of EAH during the 2002 Boston race."A similar case of an EAH-related death during the London Marathon last month indicates that our work is far from over," Siegel said.