Teitelbaum et al performed a randomized, double-blind, placebo controlled, intent to treat study on 72 FM (69 also met CFS criteria) patients (38 active and 34 placebo) that documents the effectiveness of an integrative treatment approach to CFS and FM that includes low dose cortisol (7.5-20 mg/day) (120).
The patients underwent an integrative multi-system treatment protocol based on an algorithm that took into account laboratory tests as well as signs and symptoms. Potential treatments included antidepressants, levothyroxin, cortisol, fludrocortisone, DHEA, testosterone and antimicrobial treatments.
Cortisol was administered if there was a baseline cortisol level ≤ 12; the ACTH stimulated cortisol increase was < 7 at 30 minutes, < 11 at 60 minutes or the 60 minute cortisol was < 28; the HgbA1C was < 5.1; or if patients had three significant symptoms consistent with adrenal dysfunction. Cortisol was given to 29 of the 38 patients at some time during the 3 month study.
Overall, patients had significant improvements vs. placebo in visual analog scores (p < 0.0002), the Fibromyalgia Impact Questionnaire (p <0.0005), the tender point index (p < 0.0001) and overall response (p < 0.0001).
No patients were found to have any adrenal suppression with post-treatment ACTH stimulation tests.
While this study does not separate out cortisol’s overall effect, it provides the basis for demonstrating that an integrative multi-system treatment approach that includes low dose cortisol is highly safe, effective and appropriate in the treatment of these conditions.
This integrative approach is now considered by many who specialize in the treatment of CFS/FM to be the current basic standard of care.
Conclusion
There is a complex interaction of HPA axis dysfunction in these patients, and it is becoming clear that the majority of
patients with CFS and FM suffer from clinically significant adrenocortical dysfunction. Current methods of testing are
very poor at assessing the area of dysfunction in these complex interactions, but despite this, all studies utilizing IST, CRH and/or metyrapone testing have shown abnormal results in these patients.
Studies that utilize 24-hour urinary
cortisol levels have consistently shown HPA axis dysfunction with only a few studies showing normal levels in CFS and
FM patients.
On the whole, ACTH stimulation testing has
shown to be abnormal in about 50% of CFS/FM patients. This would be the expected percentage if 100% of the patients had
HPA axis dysfunction of central origin, as this test suffers from very poor sensitivity for central HPA axis dysfunction and would be expected to miss approximately 50% of these patients.
In addition, the inaccuracy of the most commonly used cortisol assay further confounds results. The ACTH
stimulation test has clearly been shown to lack sufficient sensitivity to differentiate CFS and FM patients with HPA axis dysfunction from those with normal function.
A normal result cannot be used with any confidence in these patients
to rule-out significant dysfunction; thus, it cannot be recommended as a useful test to guide treatment in these patients.
The more central acting stimulation tests are also not recommended for routine clinical use because interpretation is problematic, they are burdensome and expensive and carry
significantly more risk than the most appropriate treatment, a therapeutic trial of physiological doses of cortisol.
Physiologic replacement of cortisol at doses of 5-15 mg/day have been shown to be safe, with little or no associated risk, and have the potential for significant clinical benefit.
Cortisol treatment carries significantly less risk and a greater potential for benefit than treatments considered to be the
standard of care in the treatment of CFS/FM, including anti-depressants, muscle relaxants and narcotics.
The current evidence supports the use of physiologic doses of cortisol as an
appropriate component of a multi-system treatment protocol for CFS and FM, and a therapeutic trial of cortisol should be
considered in the majority of these patients, especially those with signs or symptoms consistent with adrenal dysfunction,
low blood pressure and/or serum levels that are low or in the low normal range.
