Dr. Sarah Myhill* is a UK-based fatigue specialist/researcher who sees ME/CFS as stressor-induced mitochondrial dysfunction (see “Mitochondrial dysfunction and the pathophysiology of ME/CFS”). Comparing the body to a car, she describes the cells’ energy-producing mitochondria as the engine, thyroid as the accelerator, and the adrenal system as the gear box (June 2012 update).
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 [breakdown of large molecules into smaller ones to release energy].
• 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 necessarily a good thing! Both cortisol and DHEA are essential for life – too little cortisol causes the life threatening 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 test(1). By measuring and supplementing within the physiological [up to and not exceeding normal] 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. [A typical CFS Adrenal Stress Profile test result showing low levels of cortisol and DHEA is depicted on page 94 of Dr. Myhill’s free online book Diagnosing and Treating Chronic Fatigue Syndrome.] Stress responses have been elegantly documented by Hans Selye – indeed he first coined the term “stress.”
Interpretation of The Adrenal Stress Index 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 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 normal 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 “Blood Sugar and Hypoglycemia – 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 hypoglycemia, 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 there 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 program of rest and rehabilitation.
In Addison’s disease there is complete failure of the adrenal gland not because of chronic stress but because of autoimmunity.
This is a life threatening disorder and the patient is severely ill. The main clinical symptom is severe postural hypotension [aka POTS or dizziness when rising to an upright position, diagnosed via a Tilt Table Test] and chronic hypoglycemia.
Addison’s disease is tested for by a short synacthen test in which cortisol levels are measured before and after an adrenal gland stimulant ACTH [also known as the short or rapid ACTH test]. Many patients with CFS are given this test, which is found to be normal resulting in the patient being told their adrenal gland is fine and no action is required.
The problem with this test is it only shows where the adrenal gland is completely non-functioning – it does not diagnose partial adrenal failure or adrenal stress, and no measurements of DHEA are made. This makes it potentially misleading.
The idea with treatment with cortisol and with DHEA [supplementation] is to stay within physiological ranges – up to, but not more than, normal amounts. By doing this there are no side effects in the short or long term. Many doctors and patients recoil at the prospect of taking steroid hormones. Remember, all the side effects of steroid hormones are created by the dose. Using physiological as opposed to pharmacological doses avoids all these problems.
(A normal adrenal gland produces about 10-50mgs of DHEA daily and 20-25mgs of hydrocortisone (5-7.5mgs of prednisone) daily. Steroid side effects would appear after a few weeks of 100mgs a day or a few months at 50mgs a day. of hydrocortisone)
DHEA is available over the counter in the U.S., where the FDA has classified it as a food supplement up to a daily dose of 50mgs….
I start my patients on 12.5mgs (for small people) and 25mgs (for larger people) of DHEA a day, taken in the morning. I like to recheck a single DHEA after 3 months to make sure I am staying within physiological ranges and because a few patients need 50mg.
Cortisol again needs to be used in sub-physiological doses – i.e., up to, but not more than 10mgs a day. (Please note that the usual steroid most often used is prednisolone. 5mgs of prednisolone is equivalent to 20mgs of hydrocortisone). Both these are prescription only drugs.
After 3 to 6 months, if the patient wishes to continue taking DHEA, then levels need to be re-checked by doing a single sample salivary DHEA (you can order this test from my website – DHEA (saliva) single – and elsewhere online for those outside the UK).
Cortisol levels replete reliably well and it is not necessary to recheck cortisol levels.
As the patient improves, usually hydrocortisone can be stopped – typically after 1 to 2 years. I suspect DHEA is an acquired metabolic dyslexia – that is to say, as we age we get less good at making it.
• Young people can often stop DHEA as they improve and maintain levels,
• But older people often benefit from taking DHEA long term.
Low-Dose Hydrocortisone CFS Trial
In a randomized, controlled, crossover trial of low-dose hydrocortisone treatment for CFS (Dr. Anthony J Cleare, et al. Lancet; Vol 353, issue 9151), 32 participants, fulfilling both the Oxford and CDC 1994 criteria, completed this short-term trial. Participants received 5mg or 10mg of hydrocortisone for 28 days and placebo for 28 days.
The results revealed modest, statistically significant improvements in fatigue with this low-dose hydrocortisone treatment compared with placebo. The degree of disability was also reduced with hydrocortisone treatment but not with placebo. There was no significant difference in changes in fatigue score when 5mg and 10mg doses were compared.
The authors suggest that, in view of the lack of dose response in this study, 5mg is a sufficient low dose of hydrocortisone.
Participants who responded to this hydrocortisone treatment did not differ from “non-responders” in terms of their pre-treatment cortisol levels. Although none of the participants in this study had a current psychiatric illness, those who responded to hydrocortisone treatment had fewer psychiatric symptoms prior to treatment.
Based on the results of the insulin stress test, this short-term, low dose hydrocortisone treatment was not found to cause significant suppression of adrenal gland function. None of the participants dropped out of the study and only minor side effects were reported.
The authors conclude that this low-dose hydrocortisone treatment resulted in “significant reduction in self-rated fatigue and disability in patients with chronic fatigue syndrome.”
This study sheds interesting light on the possible role of low cortisol levels in the disease processes involved in CFS. Caution is required, however, in interpreting the results. Participants’ baseline cortisol levels could not predict their response to hydrocortisone treatment, and participants appeared to have baseline cortisol levels within the normal reference range.
In another randomized controlled trial of low-dose hydrocortisone therapy in CFS, McKenzie, et al. used a higher “low-dose” hydrocortisone treatment of 25 to 35mg daily. They found that this dose was associated with some improvements in symptoms but caused significant adrenal suppression.
Neither of these research teams currently recommended the use of hydrocortisone as a treatment for CFS. The Cleare study assessed the effects of hydrocortisone treatment in the short-term only. As the authors point out, further studies involving longer durations of treatment and follow-up [would be] required to assess the long-term effectiveness and safety of this treatment.
[Ed Note: Also on the high-profile subject of cortisol in ME/CFS, see “Recalibrating ‘fight or flight’ – counter-intuitive new treatment for chronic fatigue syndrome & other chronic stress disorders”, summarizing a recent report by Drs. Ben-Zvi, Vernon, and Broderick, suggesting a therapy that “challenges the conventional strategy of supplementing cortisol levels” for some patients.]
* Dr. Sarah Myhill, MD, is a UK-based fatigue specialist focused on nutrition and preventive medicine. This information is reproduced with kind permission from her educational website (DrMyhill.co.uk)® Sarah Myhill Limited, Registered in England and Wales: Reg. No. 4545198. For ME/CFS patients, a special feature of Dr. Myhill’s site is her free online book – “Diagnosing and Treating Chronic Fatigue Syndrome.” See also Dr. Myhill’s groundbreaking paper with Drs. John McLaren-Howard and Norman Booth, published June 30, 2012 – “Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)” – establishing that ME/CFS symptoms are in part due to measurable mitochondrial dysfunction, with “two main groups differentiated by how cellular metabolism attempts to compensate.”
1. Information on the Adrenal Stress Profile salivary test kit is available for residents of North America, Australia/New Zealand, and other international areas at Metametrix.com, and for those in the UK via Dr. Myhill’s website.
Note: This information has not been evaluated by the FDA. It is general information, is not intended as medical advice or to replace the attention of a personal physician, and is not meant to prevent, diagnose, treat or cure any condition, illness, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.