Hydrocortisone (Cortef)

From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' <a href="https://sites.google.com/site/cfstestingandtreatmentroadmap/home">https://sites.google.com/site/cfstestingandtreatmentroadmap/home</a>
reduces fatigue.<a href="http://www.ncbi.nlm.nih.gov/pubmed/9989716" target="_blank" rel="nofollow">1</a>

Medmedium warns against steroids

From: <a id="null" class="null" href="https://jamanetwork.com/journals/jama/fullarticle/188004">https://jamanetwork.com/journals/jama/fullarticle/188004</a>

The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P=.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001).

Conclusions.— Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS.

n a randomized, double-blind, placebo-controlled trial in CFS, low-dose hydrocortisone treatment was associated with improvement in symptoms as measured by change in Wellness scores. This is the first such study, to our knowledge, to demonstrate improvement with a drug treatment of CFS.

Significant therapeutic benefit, however, was not evident by changes in other self-rating scales. More important, what little improvement might be attributable to hydrocortisone treatment was achieved at the expense of significant adrenal suppression. Twelve of 33 patients randomized to hydrocortisone, but none of 33 placebo recipients, showed suboptimal responses to cosyntropin challenge at the end of treatment (P<.001 by 2-sided Fisher exact test). Although steps were taken to avert serious or potentially life-threatening adrenal insufficiency in the face of emergent stress, the fact that it could happen with less cautious widespread use precludes the present regimen of hydrocortisone or comparable doses of other systemic corticosteroids as acceptable choices for the prolonged treatment of CFS.

Other conclusions can be drawn from the study as well. First, many placebo recipients demonstrated some improvement on the Wellness score, as chance alone might predict; however, the magnitude of that improvement was small. Patients with CFS simply do not improve much through an observation period of 3 months. In this regard, the present data define thresholds of spontaneous clinical change that will prove invaluable in projecting sample size and study design in further trials. Specifically, the percentages of placebo recipients exhibiting 5-, 10-, and 15-point improvements in Wellness scores were 29%, 14%, and 6%, respectively.

Second, many subjects who were referred for this study proved ineligible for enrollment. Nearly 25% (151/638) did not meet CDC case criteria for the diagnosis.<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-2" data-tab-toggle=".tab-nav-references">2</a>Clearly, there remains considerable variability in how the case criteria are applied in the community.<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-7" data-tab-toggle=".tab-nav-references">7</a> Another major reason for nonenrollment was the patients' perceived need for other medications. It is always difficult to know how fastidious one should be in designing a therapeutic trial like this one. To allow concomitant medications might better approximate the setting in which a new treatment will be used in the community, but it will add confounding issues that could complicate interpretation of adverse reports and treatment outcome. Clearly, our decision to select subjects who withheld many other medications might have excluded the sickest subjects. Nevertheless, the results of the present study should be applicable to the typical CFS patient population because the degree of disability and clinical characteristics of those enrolled (<a class="figure-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#JOC80695T1" data-tab-toggle=".tab-nav-figure-table">Table 1</a>) so well emulates that of other published CFS cohorts.<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-10" data-tab-toggle=".tab-nav-references">10</a>,<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-29" data-tab-toggle=".tab-nav-references">29</a>-<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-29" data-tab-toggle=".tab-nav-references">31</a>To improve the homogeneity of the patient sample, enrollment was restricted to patients whose fatigue arose relatively acutely. As it turned out, less than 5% of subjects screened reported onset of their illness over a period of longer than 6 weeks. Moreover, that no patients screened were excluded for using systemic corticosteroids precludes the possibility that study enrollment was biased toward those less likely to respond to hydrocortisone.

Third, the present data indicate that prolonged, low-dose daily glucocorticoid use has risks. There are, to our knowledge, no other placebo-controlled trials of prolonged daily hydrocortisone treatment involving doses as low as those used here (25-35 mg, equivalent to approximately 6 mg of prednisone). Low-dose glucocorticoid replacement, defined as 20 to 40 mg of hydrocortisone in divided daily doses, was felt to be safe, to cause no symptoms other than occasional gastric distress, and to benefit patients with chronic fatigue.<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-32" data-tab-toggle=".tab-nav-references">32</a> We found that low-dose hydrocortisone treatment has mild side effects (<a class="figure-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#JOC80695T3" data-tab-toggle=".tab-nav-figure-table">Table 3</a>) and affords minimal therapeutic benefit for CFS, but significantly suppresses adrenal responsiveness.

Fourth, the data bear importantly on the basic hypothesis under which this study was undertaken, namely that CFS symptoms are perpetuated through suboptimal activity of the HPA axis.<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-15" data-tab-toggle=".tab-nav-references">15</a> That the basal and stimulated-cortisol levels did not correlate with illness severity in this study (data not shown), nor were they predictive of clinical improvement or response to treatment, argue against the hypothesis. The fact that there was evidence of symptomatic benefit in hydrocortisone recipients, however, is concordant with this hypothesis, and yet the limited benefit indicates that mere supplementation of cortisol is not sufficient. It is possible that a more salutary effect would derive from a different low-dose regimen, or from specific supplementation of corticotropin-releasing hormone or pharmacologic augmentation of its release, were these latter options to become feasible.<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-33" data-tab-toggle=".tab-nav-references">33</a>,<a class="ref-link section-jump-link" href="https://jamanetwork.com/journals/jama/fullarticle/188004#REF-JOC80695-34" data-tab-toggle=".tab-nav-references">34</a>