Chronic fatigue syndrome: a form of Addison’s disease

D ear S ir, Evengård et al.'s article [1] on chronic fatigue syndrome (CFS) is disappointing, because in their review, despite its 15 pages and 165 references, there is not a single word about the staggering similarity between CFS and Addison's disease. As someone whose CFS symptoms resolved dramatically with an old remedy for Addison's disease [2], I understandably found that review even more disappointing. To compensate for Evengård et al.'s failure to mention both the impressive overlap of CFS with Addison's disease and its clinical implications, I summarize here these issues. CFS and Addison's disease share 36 features [3–6]. Three others, however, are to be added. In fact, reduction in adrenal gland size [7], antibodies against the adrenal gland [8] and respiratory muscle dysfunction [9], besides being present in CFS [7–9], have also been found in Addison's disease [10–12]. In view of the 39 features that CFS shares with Addison's disease [3–12] (see Table 1), which constitute a similarity between two distinctly named diseases that is probably unequalled in the medical literature, it seems arguable that CFS should practically be viewed as a form of Addison's disease [13]. One could object that CFS patients, unlike Addisonian subjects, do not display hyperpigmentation or basal hypocortisolaemia. Neither abnormality, however, is a constant presenting feature of Addison's disease [14]. Substantially, all the symptoms listed in both the original [15] and the revised [16] case definition of CFS can also be found in Addison's disease [3–6], which clearly suggests that those symptoms merely reflect the adrenal insufficiency (inadequate production of both glucocorticoid and mineralocorticoid hormones) that CFS patients share with Addisonian subjects [13]. Of note, the 'hotly debated' psychiatric symptoms of CFS patients, instead of demonstrating that CFS is a psychiatric disorder, are solely due to their adrenal insufficiency, those symptoms being also present in Addison's disease [2], a purely physical condition. Adrenal insufficiency, intuitively, also accounts for the gastrointestinal, cardiac, haematological and hepatic abnormalities (see Table 1) shared by CFS patients and Addisonian subjects. Moreover, the adrenal insufficiency of CFS patients may also explain many abnormalities mentioned by Evengård et al. [1], such as reactivation of latent infections [6], chronic immune dysregulation [6], depressed function of natural killer cells [4] and neurally mediated hypotension [17]. Finally, there is no reason to exclude that other abnormalities mentioned by Evengård et al. [1], such as upregulation of the 2–5 A synthetase/RNase L antiviral pathway and hypoperfusion of the brain stem, will prove to be additional consequences of CFS patients' adrenal insufficiency. The clinical implications of the astonishing similarity between CFS and Addison's disease are obvious: CFS patients should be treated with low doses of both hydrocortisone (a glucocorticoid) and fludrocortisone (a mineralocorticoid) [3], the two steroids that are routinely administered to Addisonian subjects to correct their chronic deficiency of both glucocorticoid and mineralocorticoid hormones [3]. Evengård et al. [1] state that 'low-dose hydrocortisone was associated with some improvement in symptoms but the degree of adrenal suppression precludes its practical use for CFS'. Unfortunately, the authors of the study cited by Evengård et al. actually used inappropriately high doses of hydrocortisone [18], thereby rendering adrenal suppression unavoidable. Other researchers, who really used low doses of hydrocortisone, found that this treatment was effective and did not cause adrenal suppression [19]. Fludrocortisone, if administered properly [20], has already proved to be highly beneficial to CFS patients [17]. At this point, the first investigation of the effects of both hydrocortisone and fludrocortisone on CFS symptoms appears to be urgently needed [3]. Received 31 December 1999; accepted 2 February 2000.