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Is Chronic Fatigue Syndrome Related to Stress Response?

  [ 257 votes ]   [ Discuss This Article ] • October 10, 2003

Subtle alterations of a hormonal stress response system called the HPA axis may play a role in chronic fatigue syndrome, according to a study in the November/December 2002 issue of Psychosomatic Medicine.

A smoothly functioning hypothalamus-pituitary-adrenal, or HPA, axis helps the body remain stable under physiological and psychological stress through the actions of three hormones. First, the brain portion called the hypothalamus secretes a hormone that stimulates the pituitary gland to secrete a second hormone. This second hormone causes the adrenal glands to create cortisol.

Problems can occur at any point in this process and result in a variety of diseases. A research team led by Jens Gaab, Ph.D., of the Center for Psychobiological and Psychosomatic Research at the University of Trier in Trier, Germany; and the Institute of Psychology at the University of Zürich in Switzerland are proposing that chronic fatigue syndrome may be one of them.

Chronic fatigue syndrome is characterized by debilitating fatigue that can include including muscle aches, low-grade fever and sleep disturbances. Its cause is not understood.

Gaab and colleagues recruited approximately 40 study participants between the ages of 30 and 50. Half of the participants were chronic fatigue sufferers and the other half were healthy volunteers. All participants completed questionnaires measuring fatigue, depression and coping skills.

To examine the HPA axis in action, participants were given blood, cardiovascular and saliva tests before and after taking two stress tests. The first, a psychosocial stress test, involved preparing for a fake job interview and completing an arithmetic problem before an audience while under the impression they were being videotaped. The second test measured physical stress on a stationary bicycle.

Participants were also given a series of insulin injections known as the insulin tolerance test. "The ITT is considered the gold standard for testing the integrity of the entire HPA axis," Gaab says.

The researchers found significantly lower response levels of one of the HPA hormones, called ACTH, among the chronic fatigue patients compared with the healthy volunteers, during both stress tests as well as the ITT test. In fact, the chronic fatigue patients had significantly lower levels of the hormone before the testing even began.

"These results suggest that on a central level, subtle dysregulations of the HPA axis exist" in chronic fatigue syndrome patients, Gaab says, adding that future studies should include repeated evaluation of the HPA axis over the course of the syndrome.

Gaab and colleagues note that the possible role of cortisol in chronic fatigue syndrome still merits investigation, as low doses of hydrocortisone have shown some positive results in chronic fatigue patients.


Gaab J, Huster D, Peisen R, Engert V, Heitz V, Schad T, Schurmeyer TH, Ehlert U. Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation. Psychosom Med 2002 Nov-Dec;64(6):951-62

Source: Center for the Advancement of Health (via

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