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Chronic unexplained fatigue
  1. R Baschetti
  1. Retired Medical Inspector of the Italian State Railways, CP 671, 60001–970 Fortaleza (CE), Brazil; baschetti{at}

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    I found the editorial on chronic fatigue syndrome by White both surprising and disappointing, because he used the title “Chronic unexplained fatigue” and the subtitle “A riddle wrapped in a mystery inside an enigma”, but his editorial, by ignoring very important facts about chronic fatigue syndrome, actually perpetuates that riddle, rather than helping to solve it.1

    If a puzzling and poorly manageable condition shares more than 40 features, including all of its diagnostic criteria, with a well known and easily treatable disease, this astounding clinical overlap should not be ignored, because reason not only suggests that the mysterious illness may simply be a form of the well known disease, but also hints that it is worthwhile assessing whether the classic therapy for that treatable disease could be effective for the enigmatic condition as well.

    It is surprising, therefore, that in White's editorial there is not a single word about the 41 features that chronic fatigue syndrome shares with Addison's disease,2 including chronic fatigue and all the physical signs and symptoms, neurocognitive dysfunctions, depressive complaints, and sleep disturbances listed in the diagnostic criteria for chronic fatigue syndrome.3 Nor is there a single word about the endocrine and adrenal abnormalities that chronic fatigue syndrome shares with Addison's disease—namely, hypocortisolism, impaired adrenal cortical function, reduced adrenal gland size, and antibodies against the adrenal gland.3

    What is really mysterious about chronic fatigue syndrome is the fact that, despite its unequalled clinical overlap with Addison's disease (which, notably, does not necessarily include hyperpigmentation as a presenting feature3), no published study tried to determine whether the classic therapy for Addison's disease—that is, hydrocortisone plus fludrocortisone, could also be effective for treating chronic fatigue syndrome. Since both of these steroids, administered separately in low doses4 and in the proper form,5 have already been reported to be safe and remarkably beneficial in the treatment of chronic fatigue syndrome,3 it is even more mysterious that the effects of their combined administration on patients with the syndrome have yet to be investigated.

    As someone whose chronic fatigue syndrome symptoms, after their reported dramatic resolution thanks to an old remedy for Addison's disease,2 are currently suppressed most effectively by low doses of both hydrocortisone and fludrocortisone, I cannot but suggest that chronic fatigue syndrome, far from being “a riddle wrapped in a mystery inside an enigma”, is merely a mild form of Addison's disease.


    Author's reply

    I am pleased to learn that Dr Baschetti's “chronic fatigue syndrome symptoms . . ..are currently suppressed most effectively by low doses of both hydrocortisone and fludrocortisone”, but I would not share his confidence in this being the answer to treating the syndrome. There is little evidence that chronic fatigue syndrome is “merely a mild form of Addison's disease”.

    Two systematic reviews (published together) of blindly assessed, randomised controlled trials of these drugs found that fludrocortisone was ineffective and that there was insufficient positive evidence to recommend hydrocortisone.1 Hydrocortisone caused serious adverse effects in some patients.

    Although most studies do find a down-regulated hypothalamic-pituitary-adrenal (HPA) axis in patients with chronic fatigue syndrome, compared with healthy controls,2 this could be the consequence of the relative inactivity or insomnia that occurs with chronic fatigue syndrome, rather than being a primary event.3,4 We should also remember that a down-regulated HPA axis is found in many conditions in medicine that have nothing to do with Addison's disease.4