Orthostatic Hypotension and Chronic Fatigue Syndrome

To the Editor: Dr Rowe and colleagues¹ found fludrocortisone acetate to be ineffective for treating chronic fatigue syndrome (CFS). This is in sharp contrast with the results of my previous study, which found that fludrocortisone was remarkably beneficial for patients with CFS.² Rowe et al, by administering the commercial tablets of fludrocortisone in the inappropriate form of capsules may have biased their results, because the dissolution times of tablets that are repackaged as capsules are strikingly prolonged.³ I have stated previously that "[s]lowing down the dissolution rate of a commercial drug used as a control in a clinical trial could severely bias the results of such trials."³ Administration of fludrocortisone in the improper form of capsules could also have prevented the drug from acting synchronously with the peak absorption of sodium-containing foods. This timing may be important because it could allow mineralocorticoid drugs such as fludrocortisone to maximize their sodium-retaining actions.³

The decision by Rowe et al to coadminister tablets of potassium chloride with fludrocortisone on the grounds that "fludrocortisone increases urinary potassium excretion"¹ also may have biased their results. Chronic fatigue syndrome shares at least 39 clinical features with Addison disease, including all the symptoms listed in the diagnostic criteria for CFS, as well as many adrenal abnormalities (hypocortisolism, impaired adrenal cortical function, reduced adrenal gland size, and antibodies against the adrenal gland).⁴ It is likely that patients with CFS tend to develop hyperkalemia, just as do those with Addison disease, who obviously do not require potassium supplementation, despite long-term use of fludrocortisone. It was thus probably unsound to administer tablets of potassium chloride to patients with CFS,¹ whose orthostatic hypotension and postural tachycardia merely reflect their adrenal insufficiency, which by itself causes abnormal potassium retention.

It has recently been reported that patients with both CFS and those with Addison disease have increased sensitivity to chemical exposures.⁵ In view of this growing overlap between the 2 diseases, it is increasingly puzzling that no study has attempted to assess whether the combined administration of fludrocortisone and hydrocortisone, the 2 classic steroids to treat Addison disease,⁴ could be substantially effective for patients with CFS too. I first suggested this² after my reported dramatic recovery from CFS after eating licorice, which is a traditional remedy for Addison disease.^{2 - 3}