Adrenal

From: <a href="http://www.vitality101.com/health-a-z/Hormones-adrenal_problems_in_cfs">Adrenal Problems in CFS | Vitality 101</a>

Further supporting the use of low-dose cortisol in these patients is the fact that such therapy has been shown to improve the HPA axis response in these patients. This is counterintuitive to what physicians are taught and have found with higher pharmacological doses of glucocorticoids. In a study published in the 2001 Journal of Clinical Endocrinology & Metabolism entitled Hypothalamo-Pituitary-Adrenal Axis Dysfunction in Chronic Fatigue Syndrome, and the Effects of Low-Dose Hydrocortisone Therapy, the authors utilized ACTH and cortisol responses to CRH, insulin stress test, D-fenfluramine and 24 hour urinary free cortisol in 37 patients with CFS and prescribed these patients low-dose cortisol. They found that the therapy resulted in significant improvement and not only was there no adrenal suppression, but rather there was an improvement in the HPA axis as documented with CRH testing. They concluded, “In this group, there was a significant increase in the cortisol response to human CRH, which reversed the previously observed blunted responses seen in these patients. We conclude that the improvement in fatigue seen in some patients with chronic fatigue syndrome during hydrocortisone (same as cortisol) therapy is accompanied by a reversal of the blunted cortisol responses to human CRH.” 8

In a randomized, double-blind, placebo controlled, crossover, intent-to-treat trial published in The Lancet, patients with chronic fatigue syndrome were prescribed low dose hydrocortisone (5-10 mg/day) or placebo. The study found significant improvements in those prescribed low dose hydrocortisone vs. placebo and 28% improved to normal levels. The authors concluded, “This study shows that low-dose hydrocortisone results in significant reduction in self-rated fatigue and disability in patients with chronic fatigue syndrome…The degree of disability was reduced with hydrocortisone therapy, but not with placebo. Insulin stress tests showed that endogenous adrenal function was not suppressed by hydrocortisone.” 9 This demonstrates the effectiveness and appropriateness of this therapy.

Another randomized control trial published in JAMA also found significant improvement in fatigue scores with hydrocortisone replacement, but they used excessive dosing of 25-35 mg of cortisol. It is recommended that dosing be limited to 10-20 mg/day, as these doses have been shown to not be associated with any untoward effects and carries little to no risk of adrenal suppression.10,23,30,31 This considerable safety and negligible risk is also confirmed in endocrinology texts.54

Bashetti has published a number of studies on cortisol and CFS. He writes in the Journal of Endocrinology and Metabolism, “Hydrocortisone, the glucocorticoid that is routinely prescribedto correct the chronic cortisol deficiency of patients withAddison’s disease, has recently been confirmed tobe significantly effective also in the therapy of chronicfatigue syndrome (CFS). This comes as no surprise if we considerthat CFS and Addison’s disease share 26 features.” 41

A randomized, double blind placebo-controlled, intent-to-treat study by Teitelbaum published in the Journal of Chronic Fatigue Syndrome documented the effectiveness of an integrative therapy approach to CFS and FM that includes low-dose cortisol (7.5-20 mg/day). The authors conclude,” Significantly greater benefits were seen in the active group than in the placebo group for all primary outcomes. Using an integrated therapy approach, effective therapy is now available for FMS/CFS.” 31

A subsequent editorial in the peer reviewed, Journal of the American Academy of Pain Managementreviewed this study and agreed that an integrative approach that includes low-dose cortisol is the standard of care for these conditions. The author states, “The study by Dr. Teitelbaum et al. and years of clinical experience makes this approach an excellent and powerfully effective part of the standard of practice for therapy of people who suffer from FMS and MPS [myofacial pain syndrome]— both of which are common and devastating syndrome.” 48 The consensus opinion among those who are experts in addressing CFS and FM is that a therapy approach that includes low-dose cortisol is the standard of care.

A subsequent commentary by Teitelbaum published in JAMA states, “Our previously published pilot study and the work of Jefferies suggests that using low-dose hydrocortisone in CFS as dosages of 7.5 mg to 20 mg/day is safe and effective. These low dosages have not caused adrenal suppression…We recently completed a randomized, double-blind study that tested the effectiveness of prescribing therapy for hypothalamic dysfunction in an integrated manner for patients with fibromyalgia and CFS. This included addressing suspected hormonal deficiencies (including low hydrocortisone) and the sleep disorder simultaneously. Using this protocol in 72 patients resulted in a significant improvement in active vs. placebo group.” 42 Cortisol replacement appears to be an essential part of a comprehensive therapy approach that can be used successfully in addressing CFS and FM.31,42

A study published in JAMA found that nearly half of the patients prescribed mineralcorticoid reported complete or nearly complete resolution of CFS symptoms.43

The safety of low dose glucocorticoids was addressed in a 48 page review article published in last month’s Annals of Rheumatic Diseases entitled Low-dose glucocorticoid therapy in rheumatoid arthritis- A review on safety: published evidence and prospective trial data. This extensive review assessed the incidence and severity of adverse effects of long-term low-dose glucocorticoid therapy in rheumatoid arthritis. This review considered low dose as any dose below or equivalent to 40 mg hydrocortisone (this patient received a fraction of this dose 10mg/day). They concluded, “Adverse-effects of glucocorticoids are abundantly referred to in literature. However, in the available literature on low-dose glucocorticoid therapy very little of the commonly held beliefs about their incidence, prevalence and impact of GC [glucocorticoid] proved to be supported by clear scientific evidence. Additional data from the randomized controlled clinical trials reviewed showed that the incidence, severity and impact of adverse effects of low dose glucocorticoid therapy in rheumatoid arthritis trials are modest, and often not statistically different to those of placebo.” 10

Low-dose cortisol has been shown to improve immunity, as opposed to the well known immunosuppressive effect of pharmacological doses of glucocorticoids, 23,30,45,46 and has been shown to improve recovery from chronic infections such as EBV.47,22,29

In summary, it is becoming clear that the majority of patients with CFS and FM suffer from clinically significant adrenocortical dysfunction and that physiologic replacement of cortisol is an appropriate intervention in these patients. Cortisol doses of 15-20 mg/day have been shown to be safe, with little associated risk including adrenal suppression, and have the potential for significant clinical benefit. The current evidence supports the use of physiologic doses of cortisol in addressing CFS and FM, and a therapeutic trial of cortisol should be considered in these patients, especially those with basal cortisol levels less than 12 ug/dl.