Common Hormonal Problems in CFS - Adrenal
Underactive adrenal gland (DHEA and cortisol)
If the pituitary gland is underfunctioning then the adrenal gland will also under-function. However the gland itself may fail as a result of chronic stress.
The Hungarian physiologist Hans Selye showed that if you stressed rats, their adrenal glands enlarged to produce more stress hormones (cortisol and DHEA) to allow the rat to cope with that stress. If the rat had a break and a rest, then the adrenal gland would return to its normal size and recover. However if the rat was stressed without a break or a rest, he would be apparently all right for some time, but then suddenly collapsed and died. When Selye looked at the adrenal glands, they were shrivelled up. The glands had become exhausted.
The same thing happens in CFS. The Western way of life is for people to push themselves more and more. Many can cope with a great deal of stress, but everybody has their breaking point. 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. When the gland becomes exhausted, CFS develops and tests classically show low levels of cortisol and DHEA.
DHEA has only recently been looked at because it was not realised that it had any important actions. But the sequence of events is as follows.
- -> pregnenolone -> progesterone -> cortisol
- > -> DHEA -> androstenedione -> testosterone
- -> -> Oestrone -> Oestrodiol
- > -> DHEA -> androstenedione -> testosterone
- -> pregnenolone -> progesterone -> cortisol
DHEA is an anabolic steroid, that is to say it builds up tissues, in contrast to cortisol, which is catabolic and breaks down tissues. Both are essential for life in the right amounts: too little causes problems, as does too much. Research suggests it protects against the development of osteoporosis, which is a major consideration since all CFSs are at risk of this because of their inability to exercise.
Testing the adrenal gland for cortisol and DHEA levels
In order to ensure the right amounts of both hormones, they must be measured. This can be done with the adrenal stress profile (ASP) test. By measuring and supplementing within the physiological range, with biologically identical hormones, there are no side effects.
The ASP test looks at cortisol and DHEA levels over 24 hours. This test is available through NPTech laboratory (I can send you a kit, cost £70) and 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. DHEA is available over the counter in the USA, where the FDA has classified it as a food supplement up to a daily dose of 25mgs. It is better absorbed under the tongue - often the dose can be halved if taken in this way. This works because sublingual doses bypass the liver where DHEA is detoxified - the so-called "first pass effect". DHEA can be purchased from PharmWest and other suppliers. Cancer patients have been given up to 3,500mgs a day for some years, apparently with no side effects. By comparison, a normal person produces 20-30mgs a day of cortisone, side effects appear after a few weeks of 100mgs a day or a few months at 50mgs a day.
Interpretation of the adrenal stress profile test for DHEA and cortisol levels
DHEA is easy. Low levels mean a deficiency and DHEA supplementation is indicated. Sometimes I see a raised DHEA. This can occur in polycystic ovary disease in women and if there were symptoms suggestive of this (irregular periods, lower abdominal pain, infertility) then an ultrasound scan of the pelvis is indicated. Otherwise no treatment is known for high DHEA.
Cortisol is more awkward. Levels 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:
- Normal levels of cortisol and DHEA. Normal result. Normal adrenal gland.
- Raised cortisol, normal DHEA. This indicates a normal short term response to stress. So long as the stress is removed, the adrenal gland will recover completely. The adrenal gland is functioning normally but the patient is acutely stressed.
- 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 a normal response to chronic stress. However the patient needs a long break from whatever that chronic stress may be - insomnia, mental, physical or emotional overload, poor diet or whatever. Failure to correct leads to exhaustion. 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.
- 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. Very low levels indicate Addison's disease - complete adrenal failure. Untreated Addison's disease inevitably results in death.
- 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.
In practice, the interpretation is often not so straightforward because cortisol levels fluctuate through the day in response to the stresses of daily life, peaking in the morning and falling as the day progresses.
After 3 months on DHEA, levels need to be re-checked.
Prescribing hydrocortisone for CFS
In patients in which the ASP shows a deficiency of cortisol, it is worth trying hydrocortisone. This is the biologically identical hormone and if given in small doses (5-10mgs in the morning) has no side effects and no suppression of the adrenal gland. There is no need to carry a steroid card, no long term side effects and no need to tail the dose off once stopped. I see hydrocortisone as a crutch to the adrenal gland - it allows it to rest as little before resuming normal production after several months or years once the sufferer is considerably better. There is no need to recheck levels of cortisol once on treatment.
A new hydrocortisone trial
A randomised, controlled, crossover trial of low-dose hydrocortisone treatment for CFS has been published. 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 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 randomised controlled trial of hydrocortisone therapy (see Interaction 29, page 21 for a review), McKenzie at al., used a higher 'low-dose' hydrocortisone treatment of 25 - 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 hydrocortone as a treatment for CFS. The present 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 are required to assess the long-term effectiveness and safety of this treatment.
For those with secondary hypothyroidism (indicated by low or normal TSH but low T4 and T3) or suspect secondary hypoadrenalism due to poor pituitary functioning, low dose DHEA may prove helpful. A patient of mine has found that a really very low dose (3 - 5mg per day) can make an astonishing difference to quality of life. Please see this link for more detail:
A patient of mine recently (October 2014) brought to my attention a 1999 pilot study employing DHEA in the treatment of CFS, which was published in the Journal of Clinical Rheumatology. You will find further details here:
- ↑ Cleare et al; The Lancet, 1999, Vol. 353 February 6, p455-458.
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