Combining Hydrocortisone and Fludrocortisone - Could it be an effective treatment for ME/CFS?

Dr Charles Shepherd

The cause and significance of Hypocortisolism in ME/CFS (i.e. decreased production of the hormone cortisol from the adrenal glands) remains the subject of debate. All of the evidence so far indicates that the cause is more likely to be central (i.e. in the brain) rather than the peripheral (i.e. at the level of the adrenal glands, where the hormone is produced). In other words, the adrenal glands don’t seem to be receiving enough in the way of stimulatory messages from higher centres in the brain (in particular, the hypothalamus gland - the ‘leader of the hormonal orchestra’), and this results in a reduced output of cortisol.

Low levels of cortisol also occur in an interesting and rare condition known as Addison’s disease, but are much more severe and potentially life threatening. Even so, Addison’s disease has a number of very similar clinical features to ME/CFS (i.e. fatigue, muscle weakness, dizziness and hypotension/low blood pressure). As a result, there have been a number of attempts to see if the type of hormonal treatments used in Addison’s disease (i.e. hydrocortisone and fludrocortisone) might be effective in ME/CFS.

Two clinical trials have examined the use of hydrocortisone alone in ME/CFS patients. An American trial (ref: Journal of the American Medical Association, 1998, 280. 1061 - 1066) reported an improvement in general health but not in activity, depression, mood or symptom measures. A UK trial (ref: Lancet 1999, 353, 455-458), using a lower dose of hydrocortisone, also reported some degree of improvement in fatigue, symptoms, and disability level. Of some concern was the fact the American trial found evidence of adrenal gland suppression (i.e. the output of natural cortisol had been suppressed by the synthetic hormone). Two trials (refs: Archives of Internal Medicine, 1998, 158, 908-914; Journal of the American Medical Association, 2001, 285, 52-59) have also assessed fludrocortisone alone. Neither have reported any benefits.

A research group from Belgium have now reported results from a clinical trial involving a combination of hydrocortisone (5 mg/day) and 9-alphafludrocortisone (50 mcgs/day) in ME/CFS patients (ref: American Journal of Medicine, 2003, 114,736-741). The trial involved 100 patients who met Fukada et al research criteria for CFS. It was randomised, placebo-controlled, double-blinded and crossover (i.e. they had three months active treatment followed by three months placebo) in design. 80/100 patients completed the trial. Overall there was no difference in the various outcomes-including fatigue levels, general well-being, and blood pressure measurements (which the fludrocortisone may have helped to raise) - even in those patients that had the lowest of the baseline cortisol levels.

Although these results suggest that the type of combination therapy used to treat Addison’s disease is not going to be helpful in ME/CFS, the research group wisely point out that ME/CFS is a heterogeneous condition and that there could well be a subset of patients with disturbances in the hypothalamic-pituitary-adrenal axis that could respond to hormonal treatments. So further research in this area of therapeutic intervention is clearly warranted-possible by using a more carefully selected group of patients who have evidence of significant adrenal gland suppression (research by Professor Ted Dinan et al using a CT scanning has shown Psychoneuroimmunology, 1999, 24, 759-768). In the meantime, most doctors (myself included) will continue to err on the side of caution and remain reluctant to prescribe either low doses of hydrocortisone ( mainly because of fears about adrenal gland suppression - even when using a very low dose) or fludrocortisone (because of its potential side-effects)

Our thanks for this article to Dr Charles Shepherd.