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.
The adrenal gland is responsible for the body's hormonal response to stress. It produces adrenaline, which stimulates the instant stress hormone response (fight or flight reaction). It also produces cortisol and DHEA, which create the short and long term stress hormone responses. Cortisol suppresses the immune system, breaks down tissues and has a generally catabolic effect. However, these effects are balanced out by DHEA, which has the opposite effect - activating the immune system and building up tissues. All these hormones are made from cholesterol - just one reason why running a low cholesterol is not a good thing!
Both cortisol and DHEA are essential for life - too little cortisol causes the life threatening disease Addison's disease, too much causes the debilitating condition Cushing's syndrome. The name of the game is to get the right balance. To achieve this both hormones must be measured. This can be done with the Adrenal stress profile - salivary (ASP) test. By measuring and supplementing within the physiological range, with biologically identical hormones, one is not going to get any unpleasant side effects, i.e. we are trying to copy Nature and restore normality.
The ASP test looks at cortisol and DHEA levels over 24 hours. This test entails taking salivary samples through the day (yippee, no needles!). Indeed, salivary sampling is felt to be the most accurate way of assessing steroid hormone levels.
An abnormal result may be a symptom of other problems or it may cause problems in its own right. The response of the body to stress (any stress - infectious, nutritional, emotional, physical etc) is to increase the output of stress hormones. This gears the body up for action by raising blood pressure, increasing heart rate, improving mental alertness (which can cause anxiety), increasing energy supply and so on. It is actually metabolically very inefficient because it uses up lots of energy, but totally desirable if one has to fight for one's life! This reaction is essential for short term stress, but unsustainable long term. So time for rest and recovery is equally essential.
Problems arise when the stress is unremitting because eventually the output of the adrenal gland will reduce making one far less able to tolerate stress. Indeed, this is often a complaint of my CFS patients - they simply do not tolerate stress at all well.
The pattern of the result from the adrenal stress test gives some idea where one is along the stress response time line.
Stress responses have been elegantly documented by Hans Selye indeed he first coined the term "stress".
Interpretation Of The Adrenal Stress Profile Test for DHEA and Cortisol Levels
Levels of DHEA and cortisol vary according to the level of stress and for how long that stress has been applied. Increasing cortisol production is the normal response to short term stress and is highly desirable, so long as the stress is removed and the adrenal glands can recover. On-going, unremitting stress means the adrenal gland and the whole body is in a constant state of alert, does not get time to recover and eventually packs up. So, there are several stages of adrenal function gradually leading to failure:
1. Normal levels of cortisol and DHEA. Normal result. Normal adrenal gland.
2. Raised cortisol, normal DHEA. This indicates a normal short term response to stress. Typically low blood sugar - See Hypoglycaemia - the full story.
3. Raised cortisol and raised DHEA. The adrenal gland is functioning normally but the patient is chronically stressed. So long as the stress is removed, the adrenal gland will recover completely.
4. High levels of cortisol, low levels of DHEA. The body cannot make enough DHEA to balance cortisol. This is the first sign of adrenal exhaustion. This is the first abnormal response to chronic stress. The patient needs a long break from whatever that chronic stress may be - the commonest chronic stress is Hypoglycaemia - the full story, but also consider insomnia, mental, physical or emotional overload or whatever. DHEA can be supplemented to make the patient feel better, but it must be part of a package of recovery, without which worsening can be expected.
5. Cortisol levels low, DHEA levels low. The gland is so exhausted it can't make cortisol or DHEA. By this time patients are usually severely fatigued. Often these is loss of diurnal rhythm so no morning peak. This may also be associated with low melatonin at night.
6. Cortisol levels low, DHEA borderline or normal. This probably represents the gland beginning to recover after a long rest. DHEA may be used to help patients feel better whilst they continue their programme of rest and rehabilitation.
Dehydroepiandrosterone (DHEA) is a hormone that comes from the adrenal gland. It is also made in the brain. DHEA leads to the production of androgens and estrogens (male and female sex hormones). DHEA levels in the body begin to decrease after age 30 levels decrease more quickly in women, considered a possible link with higher rates of ME/CFS and Fibrormyalgia in the female population.
DHEA is labelled everything from a fountain of youth drug to fraud the uses of DHEA are getting lost in all the controversy. Adrenal support with DHEA supplementation can make a difference but there can be serious side effects it must be used appropriately in a therapeutic setting under medical supervision in support of adrenal insufficiency.
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