Reduced Cortisol Levels
The HPA axis refers to the hypothalamus, pituitary, and adrenal glands, which are part of the endocrine system. The hypothalamus secretes several hormones that control the pituitary gland. The pituitary gland is considered the "master gland" of the endocrine system because it secretes hormones that control other glands (including the ovaries, testes, adrenals, and thyroid glands).
The hypothalamus stimulates the production of corticotropin, which stimulates the production of cortisol from the adrenal glands. "Many experts now think that chronic fatigue syndrome may be an example of the hypothalamus failing to properly regulate the brain's influence on the immune system," says Jay Lombard, M.D., assistant clinical professor of neurology at Weill Medical College of Cornell University in New York City and co-author of The Brain Wellness Plan (Neeck et al. 2000).
Researchers are exploring the relationship between cortisol and central neurotransmitter function, in particular, the relationship between cortisol and 5-HT (serotonin).
A review of the CFS database at King's College (London) found that one-third of the studies that reported baseline cortisol found it to be significantly low, usually in a third of patients. Methodological differences may account for some of the varying results. More consistent is the finding of reduced HPA function and enhanced serotonin (5-HT) function on neuroendocrine challenge tests (Parker et al. 2001).
A major role of the HPA axis is to restrain the immune system and prevent tissue damage. Reciprocal interactions between the HPA axis and immune system constitute a new endocrine feedback loop that has given rise to the field of neuroendocrine immunology (Torpy et al. 1996).
An article in the Journal of Affective Disorders described a study in which cortisol levels were measured in 10 patients with CFS, 15 patients with major depression, and 25 healthy controls. Baseline circulating cortisol levels were highest in the depressed patients; lowest in the CFS patients; and intermediate between the two in the control group of 25 healthy individuals. Prolactin responses to the selective serotonin-releasing agent d-fenfluramine were lowest in the depressed patients, highest in the CFS patients, and intermediate between both in the healthy group. The authors concluded that depression is associated with hypercortisolemia and reduced central serotonin neurotransmission and suggest that CFS may be associated with hypocortisolemia and increased 5-HT function (Cleare et al. 1995).
Addison's disease results from hyposecretion of cortisol and is characterized by weakness, fatigue, and dizziness upon standing. As described below, CFS may be a mild form of Addison's disease. Blood tests can determine serum cortisol levels. Blood must be drawn in the morning and afternoon because cortisol levels are higher during the day and lower at night. Total normal cortisol levels (morning and evening) in adults are:
- 8 a.m.: 5-23 mcg/dL (138-635 nmol/L)
- 4 p.m.: 3-16 mcg/dL (83-441 nmol/L)
- 8 p.m.: less than 50% of 8 a.m. levels
Adrenal Fatigue
As noted, it has been proposed that CFS is a mild form of Addison's disease (referred to as adrenal insufficiency or hypoadrenalism). The following evidence has been presented (Jefferies 1994; Baschetti 1999; Jeffcoate 1999; Baschetti 2000):
- Many of the symptoms of CFS overlap those of Addison's disease (adrenal failure).
- Improvement in CFS patients has occurred after supplementation with mineralocorticoids (fludrocortisone), low-dose hydrocortisone (cortisol), and licorice (an old herbal remedy for Addison's disease).
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