Question

I was interested to see the item on Addison’s disease in the Winter issue of ME Essential as I have a close friend with this rare disease and it obviously has some interesting symptom overlaps with ME/CFS. So is there any evidence that adrenal gland failure, and steroid hormone production, could also be involved in ME/CFS? If so, would it be worth looking at steroids as a possible form of treatment for ME/CFS?

Answer

Addison’s disease is a rare condition where there is a serious fall in the output of a hormone called cortisol from the adrenal glands – two hormone producing glands that sit above the kidneys. Onset can occur at any age from five to 80 but is most common between 30 and 50. Because it’s so rare, some doctors have never even seen a case in their medical lifetime and so it is not something that comes to mind when a patient presents with ‘chronic fatigue'.

However, we recommend that Addison's Disease is a condition that is considered and excluded – especially where there are ‘red flag’ symptoms or signs, such as weight loss, vomiting or increased skin pigmentation, that are not consistent with a diagnosis of ME/CFS. If there is any possibility of Addison’s disease being present in someone with an ME/CFS-like illness, this should be investigated as a matter of urgency. If the result of the basic screening test for cortisol (below) is in any way suggestive of Addison’s disease, referral to a hospital hormone specialist (endocrinologist) should be arranged as soon as possible.

Common symptoms of Addison’s disease:

• • General fatigue,
  • Muscle weakness causing difficulty climbing stairs, or rising from sitting to standing,
  • Unexplained weight loss,
  • Increased or unusual areas of pigmentation on the skin especially inside the mouth and in skin creases on the palm, wrist or stomach,
  • Dizziness and blackouts,
  • Postural hypotension (falling blood pressure when moving from sitting to standing),
  • Nausea and sometimes vomiting,
  • Cognitive dysfunction.

Less common symptoms:

• • Muscle and joint pains,
  • Salt cravings,
  • Headaches,
  • Stomach pains,
  • Anxiety or depression where the diagnosis is delayed.

Addison’s disease and ME/CFS clearly have several symptoms in common. Although there is consistent research evidence to show that part of the underlying disease process in ME/CFS involves what is called downregulation of the hypothalamic-pituitary-adrenal (HPA) gland axis, and that this can cause a reduced output of the hormone cortisol from the two adrenal glands (i.e., hypocortisolaemia) which sit above the kidneys, this is not the same as the very serious reduction in cortisol production that occurs in Addison’s disease.

Testing of adrenal gland function can be done by checking the level of cortisol with a simple blood test. Because cortisol levels change throughout the day, the timing of a cortisol test is important. For basic sreening a cortisol blood test is usually done early in the morning when cortisol levels are normally at their highest.

Checking cortisol levels is one of the routine blood tests that we recommend are always carried out before a diagnosis of ME/CFS is confirmed. If the level of cortisol is low, then further testing of adrenal gland function in the form of what is called a ‘synacthen test' might be necessary. This test has to be done in hospital and involves giving Adrenocorticotropic Hormone (ACTH) that stimulates the adrenal glands to produce cortisol.

If testing for adrenal insufficiency needs to be done, this should always be arranged on the NHS. I would not recommend the use of tests that are arranged by alternative health practitioners, which can include checking salivary cortisol levels.

Although some minor benefits from the use of low doses of hydrocortisone in ME/CFS have been reported, the current consensus is that the disadvantages (including further suppression of the natural output of cortisol from the adrenal glands) of using high or low-dose steroid treatment in ME/CFS outweigh any possible benefit.

More information

• The ME Association has detailed information on these topics that can be downloaded or ordered from the website shop:
  • We explain why an early and accurate diagnosis is so important. We examine the core symptoms, the need to take into account a patient's clinical history, the need for clinical investigations and blood tests, and consider other explanations for persistent symptoms.
  • The ME Association Clinical and Research Guide (The ‘Purple Book') provides more information on this topic.
    • Addison's Disease can be found in the Differential Diagnosis section.
    • HPA dysfunction and low levels of cortisol in ME/CFS can be found in the Research section.
    • Clinical trials involving the use of hydrocortisone can be found in the Treatment and Immunological sections.
• The NHS: Addison's Disease: Symptoms, Causes, Testing, Diagnosis, Treatment – incl. the cortisol blood test and the synacthen stimulation test | December 2021