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Last updated January 1, 2014

Neuroendocrine Abnormalities in CFS Deserve More Comprehensive Study

Scientific panel issues consensus statement on research issues

Renee Brehio, CFIDS Association of America, April 23, 2001

WASHINGTON, DC-Research on the neuroendocrine system, which involves interactions between the brain and glands that secrete hormones, could help explain many of the symptoms of chronic fatigue syndrome (CFS). This was one conclusion reached by a panel of experts that convened in March for the second in a series of scientific symposia on CFS. The symposium was sponsored by The Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America and the U.S. Centers for Disease Control and Prevention (CDC).

Several studies have suggested a neuroendocrine component to CFS, but the exact role these abnormalities play is still a mystery. For example, studies have found that some CFS patients have low levels of cortisol, a hormone produced by the hypothalamic-pituitary-adrenal (HPA) axis that plays a key role in sleep and fatigue, but more recent research has not confirmed those findings.

"CFS is a multisystem disorder, and needs a multidisciplinary approach," said Dimitris Papanicolaou, MD, assistant professor of medicine, Emory University, and panel chair. "Researchers from diverse areas of study need to collaborate to answer questions about neuroendocrine involvement in CFS and drive treatment strategies to improve patients' daily lives."

Following a day of presentations by experts from around the world, an independent panel composed of researchers and practitioners in the fields of biostatistics, endocrinology, epidemiology, immunology, internal medicine, neurology, psychiatry, and sleep disorders developed a consensus statement on the key issues surrounding the role of the neuroendocrine system in CFS.

The panel agreed that:

The nature of HPA function in CFS needs to be clarified. There is evidence of HPA axis dysfunction in CFS patients, but testing has yielded inconsistent results. This may be due in part to the relapsing-remitting nature of the illness and to differences in research study designs. The panel suggested that studies comparing CFS patients with and without HPA axis dysfunction should be conducted.

Cytokine abnormalities, neuroendocrine abnormalities, orthostatic intolerance, and CFS may be interconnected. Cytokines are chemical messengers that stimulate the HPA axis when the body is under stress or experiencing an infection. A number of them, including tumor necrosis factor alpha (TNF-") and interleukin-6 (IL-6), have been implicated in CFS. The panel noted these findings are intriguing in view of research connecting CFS and a family of blood pressure-related disorders called orthostatic intolerance (OI). There is evidence that excessive secretion of inflammatory cytokines such as TNF-" may induce OI, although more studies delineating the links between these abnormalities are needed.

CFS is not synonymous with depression. The panel agreed that CFS should be differentiated from major depression. Individuals with major depression have an activated HPA axis, but HPA axis studies in CFS patients have been contradictory. Studies have shown that corticotrophin releasing hormone (CRH) levels in the cerebrospinal fluid are normal or even low in CFS patients, while they may be increased in depressed individuals. Persons with CFS also demonstrate a diminished cortisol response compared to persons with depression. The panel suggested that these data may point toward a potential biological marker for persons with CFS compared to persons with depression.

No link has been established between CFS and stress. Past research has suggested that stressors such as viral infections, traumatic life events, physical abuse, and automobile accidents may cause CFS symptoms. However, the panel agreed that there is not enough evidence to date to establish a link between specific stressors and neuroendocrine abnormalities in CFS and related disorders.

Sleep abnormalities may contribute to CFS symptoms. Sleep disturbances have been shown to cause increased production of IL-6 and TNF-", and some researchers believe that they contribute significantly to excessive daytime sleepiness in CFS. However, the panel pointed out that studies of the association between HPA axis alteration, cytokine secretion patterns, and sleep abnormalities have not yet been conducted in CFS patients.

More research is needed to define the neuroendocrine aspects of CFS. The panel outlined future research needs, including studies to: evaluate stressors previously hypothesized to cause CFS; test treatment strategies, including drugs to affect HPA axis activity; and identify neuroendocrine activity in larger populations of persons with CFS, including those that fit specific subtypes of the disease. Panelists also suggested ways to overcome potential research barriers, such as conducting long-term studies to capture the fluctuations in symptom severity most CFS patients experience and developing human experimental models that temporarily recreate the symptoms of CFS to identify potential biological markers for the illness.

The CFS assessment symposia series is designed to examine the role of the neurological, endocrine, circulatory, and immune systems in CFS. The symposia gather experts to evaluate research findings, identify the most promising next steps for research, define research and funding priorities, and create research collaboration teams.

The CFIDS Association of America, which developed the symposia series, is the nation's leading organization working to conquer this illness. Since 1987, the Association has invested nearly $12 million in education, public policy, and research programs in its efforts to bring an end to the suffering caused by CFS.

The CDC protects people's health and safety by preventing and controlling diseases and injuries, enhances health decisions by providing credible information on critical health issues, and promotes healthy living through strong partnerships with local, national, and international organizations. The agency conducts a CFS research program under the auspices of the National Center for Infectious Diseases.

CFS, also called chronic fatigue and immune dysfunction syndrome (CFIDS), is a debilitating and complex disorder characterized by profound fatigue, pain, and cognitive problems that are not improved by bed rest and may be worsened by physical or mental activity. For more information, call 1-800-442-3437 or visit




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