Altering the activity of the hypothalamic-pituitary-adrenal axis, or HPA axis, leads to altered release of CRH (corticotrophin-releasing hormone), cortisol, and other hormones. These hormones can influence the immune system and many other body systems. Producing lower levels of cortisol than healthy control subjects, similar hormonal abnormalities have also been observed among ME/ CFS patients and related disorders like Fibromyalgia. Cortisol suppresses inflammation and cellular immune activation, reduced levels might relax constraints on inflammatory processes and immune cell activation. Even though ME/ CFS patients had lower levels of cortisol than healthy individuals, their cortisol levels were still within the acceptable range of what is considered normal. Therefore, doctors cannot use cortisol levels as a diagnostic biomarker.
As mentioned above, some people with ME/CFS have abnormalities in the HPA axis, researchers are especially interested in some of the central-nervous-system chemicals and hormones controlled by the HPA axis: Neurotransmitter changes of chemicals that communicate messages with the brain. Research has shown abnormal levels of certain important neurotransmitters (serotonin and dopamine).
The stress hormone cortisol at low levels could be what makes it hard to deal with stress, either physical exertion,infections or cognitive challenges.
Disturbed circadian rhythms, a part of the HPA axis regulates the sleep-wake cycle. There is some evidence suggesting this clock is thrown off, unable to get the proper rhythm re-established the results are familiar for those affected.
Some research on HPA affects: