U.S. Department of Health and Human Services
New research has revealed hormonal deficiencies in the endocrine systems and brains of people with chronic fatigue syndrome (CFS). These findings may explain many of the symptoms of the disorder and could lead to new treatment strategies, according to scientists at the National Institute of Health and the Alcohol, Drug Abuse, and Mental Health Administration.
The study results were published this week by a collaborative team of researchers at the National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases, and the National Institute of Child Health and Human Development.
All patients diagnosed with CFS have debilitating fatigue lasting at least six months that cannot be attributed to any other disease process. Other symptoms can also include feverishness, tender lymph glands, muscle and joint aches, sleep disturbances, depression and difficulty concentrating.
The prevalence of CFS has not yet been determined, although researchers at the Centers for Disease Control and NIAID-funded investigators are currently attempting to ascertain the number of CFS sufferers in the United States. Estimates range in the tens of thousands. Most people diagnosed with CFS are young adult women, but the condition occurs in people of all ages and races and of both sexes.
The research team found that on average, levels of cortisol, a hormone produced by the adrenal gland, were lower in the blood or urine of the 30 CFS patients studied than in the 72 normal volunteers tested. The body secretes cortisol in response to stress. Physicians have long known that even a subtle deficiency of cortisol can be associated with lethargy and fatigue.
Normally, when the body responds to a stressor-whether to an infectious viral or bacterial agent, an environmental toxin, or a psychological event—a complex series of events occurs in the endocrine (hormonal) system. The hypothalamus, a small area at the base of the brain, secretes a brain chemical called corticotropin releasing hormone (CRH), which activates the pituitary gland to secrete adrenocorticotropin hormone (ACTH). ACTH, in turn, stimulates the adrenal gland to produce cortisol.
The investigators concluded, based on a series of clinical tests involving the administration of small doses of CRH or ACTH, that the cortisol deficiency seen in patients with CFS resulted from a CRH deficiency.
In addition to controlling ACTH and cortisol secretion, CRH also helps to increase energy levels though its direct effect on the brain. A CRH deficiency by itself could, then, contribute to the lack of energy seen in people with CFS.
“Two hormonal abnormalities—a CRH deficiency and the resultant cortisol deficiency would each contribute to the overall symptoms and course of CFS,” said the paper’s first author, Mark A. Demitrack, M.D., previously with NIMH and now assistant professor of psychiatry at the University of Michigan Medical School.
The endocrine deficiency found in the study patients also offers a possible explanation for the depressive symptoms that some people with CFS experience.
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“Dr. Gold noted that…there appears to be a hormonal imbalance in CFS patients.”
“Our research indicates that the lower CRH levels evident in people with CFS also occur in patients with depressive syndromes fundamentally caused by biochemical imbalances,” said Philip W. Gold, M.D., chief of NIMH’s Neuroendocrinology Branch and senior author on the paper.
These illnesses not only include those traditionally characterized as mental disorders, such as specific subtypes of major depression, but also other medical disorders. For example. Dr. Gold said, the depressive syndrome associated with Cushing’s disease and hypothyroidism also seems to occur in the context of a CRH deficiency.
“Finding a common central nervous system defect in these illnesses underscores the fact that they are all fundamentally medical disorders,” Dr. Gold said.
The investigators suggest that insufficient stimulation of certain parts of the brain by cortisol or CRH could account for the lethargy and increased need for sleep seen in people with depressive syndromes as well as in those with CFS.
Further studies are in progress to determine which contributes most significantly to the fatigue in patients with CFS—the CRH deficiency or the cortisol deficiency alone, or the CRH and cortisol deficiencies together.
Stephen E. Straus, M.D., chief of NIAID’s Laboratory of Clinical Investigation, who collaborated with the NIMH researchers on the study, has investigated various aspects of CFS for the past 12 years. He was originally intrigued by the possibility that a chronic infection could cause the disorder and lead to the high levels of antibodies to viruses that are found in many people with CFS. Antibodies are molecules produced as part of the body’s protective response to ward off infectious agents or other foreign substances.
“There continue to be hints of viruses being associated with CFS,” Dr. Straus said, “but I am excited by the alternative, new hypotheses raised about the syndrome by the current findings.”
“Because cortisol is a potent suppressor of immune responses, a mild reduction in cortisol levels could allow the immune system to remain overactive, leading to findings such as higher-than-normal antibody levels,” Dr. Straus said. Dr. Gold noted that it is important to point out that “this study does not imply damage to the endocrine glands or the brain. Instead, there appears to be a hormonal imbalance in CFS patients,” he said.
Although the research findings have not proved that low CRLH and cortisol levels cause CFS, the investigators said, their results suggest that hormonal balance might be restored by treating patients with small amounts of cortisol.
“Cortisol treatment, however, is not without hazards,” Dr. Gold said. “It would be simplistic and perhaps dangerous to treat patients with additional cortisol. If cortisol were given, it could signal to the hypothalamus that secretion of CRH is unnecessary because cortisol is in adequate supply. Thus, the CRH deficiency could be exacerbated,” he added.
Despite these concerns, Dr. Straus said, “careful study could reveal a means to use the present findings to help alleviate the associated fatigue, lethargy, muscular aches and feverishness of CFS.”
The study results were published in the December 1991 issue of the Journal of Clinical Endocrinology and Metabolism. In addition to Drs. Gold, Straus, and Demitrack, the authors include Markus J.P. Kruesi, M.D., and Sam J. Listwak, NIMH; Janet K. Dale, R.N., NIAID; and Louise Lave, M.D., and George P. Chrousos, M.D., NICHD.