ME/CFS/FM Practitioners on Hydrocortisone

In 2008, WebMD reported that Kent Holtorf MD routinely treats patients with 5-15 mg hydrocortisone.


Fibromyalgia researcher Lesley Arnold, MD, disagreed with that approach stating:

“The evidence in favor of using steroids to treat these conditions just isn’t there. We just don’t have enough consistent data about abnormalities in the HPA axis.” and that some FM patients have increased and others decreased HPA axis functioning.

Dr. Teitelbaum believes that adrenal fatigue plays a major role in ME/CFS/FM and regularly uses ultra-low (<15 mg/day) doses of bioidentical hormones. In the latest edition of “From Fatigued to Fantastic“, Teitelbaum says it often makes ME/CFS/FM patients quickly feel better. Teitelbaum says he usually goes by symptoms but that a fasting cortisol of under 14 mcg/dL, especially if ACTH is under 25 pg/mL or glycosylated hemoglobin is 5.2 or less, suggests a trial of 5-15 mg hydrocortisone is warranted.


He asserts that the fears of using the hormone date back to the early days of hormone usage when doctors, not knowing any better, vastly overdosed their patients

His patients usually take it all in the morning or about 2/3rds in the morning, and the rest around lunch.


Dr. Myhill appears to be moving more to pregnenolone but does prescribe low dose hydrocortisone (5-10 mg) in patients for whom the Adrenal Stress Profile test shows a reduction in cortisol. She states: “The use of hydrocortisone allows the adrenal gland to rest a little and, in time, resume normal production, at which point the hydrocortisone can be stopped. This removal of the hydrocortisone support should only happen once the patient feels considerably better, which may take several months or even years.”


Dr. Myhill prescribes cortisol “only in patients with a proven deficiency”. She uses 5-10 mg (rarely 15 mg) to be taken either in the morning, or morning and lunchtime. At that low of a dose, she reports that cortisol levels do not need to be monitored.

Other Possible Ways of Normalizing Cortisol Levels


Mind/body interventions may help some people normalize cortisol levels.


The evidence that behavioral modifications such as mindfulness based stress reduction (MBSR) can normalize cortisol levels is mixed, with some studies finding so and others not.  A major review, however, found that interventions like yoga, meditation, tai chi, acupuncture, mindfulness, religious/spiritual practices, cognitive behavior therapy and coping did tend to normalize cortisol levels, and were associated with reductions in inflammatory processes.


A “health education program” and three CBT studies also reportedly increased cortisol levels in their mix of “ME/CFS” patients. Another review of various interventions in fibromyalgia, however, to improve cortisol, found only “small overall effects”. A 2-month isometric yoga program in ME/CFS did improve fatigue and reduce anxiety levels but did not affect cortisol levels.

One CBT study, interestingly, found that reduced sleep duration was associated with low cortisol levels. Poor sleep has been associated with reduced morning cortisol levels before. Researchers have recognized that poor sleep could be responsible for some of the low morning cortisol levels in ME/CFS. On the other hand, cortisol does affect the sleep-wake cycle.



Two Different Approaches

Tinkering with the hormones carries real risks. The North Dakota study and the ME/CFS experts used two distinctly different approaches to hydrocortisone.. The North Dakota approach used doses more designed to snuff our inflammation than to provide adrenal support. They used a three week high dose induction period to stabilize the patients and then quickly hit flares hard with higher-dose, quickie 5-day hydrocortisone regimen. They also proposed that some patients can safely stay on the higher dose regimen over long periods of time time so long as they did not take hydrocortisone on weekends.


The doses given during the three week induction period were high enough to suggest that adrenal suppression was a  real possibility. The authors reported, though, that no adverse side effects suggestive of overdose occurred.


The North Dakota study was not rigorously done. It was not placebo-controlled or blinded; neither the doctors in the study, the disease criteria, the method of measuring symptoms, etc. were provided. The average 12 mg/day dose per patient was not explained. The study also reported that the participants in a wide variety of diseases improved by over 60% – a remarkably high number. The main source of information on adrenal suppression came from a 1957 paper. Despite the high doses given during the induction period, no tests were done to determine if adrenal suppression had occurred.


The large, rigorous studies needed to validate the safe use of low-dose hydrocortisone to battle flares have not been done.

No rationale was also given for providing the broad spectrum antibiotic to everyone who failed initially to significantly improve. That addition seemed strange given worries about antibiotic resistance and possible gut issues.


Instead of using hydrocortisone to respond to flares, the ME/CFS practitioners that prescribe low dose hydrocortisone (5-15 mgs/day) have their patients use it consistently – and at much lower doses.


The only ME/CFS hydrocortisone study to last several months did find adrenal suppression in some patients, but at much higher doses (25-35 mgs/day) than typically used by ME/CFS/FM experts 5-15 mgs/day).


While the limited evidence we do have (1 one-month study) suggests that the hydrocortisone used in this manner is safe, no data exists on the safety of long term low-dose hydrocortisone use in ME/CFS/FM. The ME/CFS/FM experts who use it do appear confident, however, that when used in low doses it is safe.


ME/CFS studies suggest that some ME/CFS patients do readily respond to everyday doses (5-15 mgs) that were significantly lower than the doses used in the North Dakota study. The higher dose, hit the inflammation hard approach used by the doctors in the North Dakota study is a very different approach indeed


The Gist

• Cortisol affects metabolism, inflammation, blood pressure, blood sugar, energy production and even the sleep-wake cycle.


• Studies generally find low cortisol levels are present in ME/CFS/FM


• A huge study involving about 80 doctors and 600 people with fibromyalgia and 25 with ME/CFS (and over a 1000 others with other diseases) found that about 75% benefitted from low dose hydrocortisone (Cortef) supplementation (<15 mgs/day).


• The study included an induction period in which everyone took hydrocortisone for a month and then a flare reduction period in which the participants took it for five days following the beginning of a flare. Some people took it throughout the month while taking a hydrocortisone holiday on weekends.


• The amount of hydrocortisone given during the three-week induction period was extremely high – up to five times higher than a dose which produced adrenal suppression in some ME/CFS patients – but over several months.


• The authors asserted that the low dose of the drug plus the holidays prevented adrenal suppression where the adrenal glands stops producing cortisol from occurring. While the authors stated that the average dose during the flare period was 12 mgs/day, if some of the participants took the drug five days a week 4 times a month they could be taking almost 20 grams a day – and be in danger of adrenal suppression.


• Tests for adrenal suppression were not done but the authors reported so signs of it occurred.


• From the simplistic monitoring system to the lack of blinding or cortisol testing etc. the study was rudimentary indeed.


• Past placebo controlled hydrocortisone studies in ME/CFS, while small, do suggest that a subset of patients may significantly benefit from supplementation. Baseline cortisol testing, does not, however, reveal who might benefit. Why some benefit and others do not is unclear.


• Several ME/CFS experts do embrace hydrocortisone supplementation in low levels (5-15 mgs. depending on the doctors.) They assert that adrenal suppression does not occur at these levels.


• Some studies have been able to use mind/body and behavioral techniques to normalize cortisol levels. Other studies have not.


• The large, long term studies needed to fully assess the efficacy and safety of low dose hydrocortisone supplementation have not occurred in these diseases.

From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment'


Reduces fatigue


For those who follow the 'new age' like teachings of the 'Medical medium' he warns emphatically against use of steroids (and offers other therapeutic approaches, some of which I have tried and found quite helpful



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.


In 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.^2^Clearly, there remains considerable variability in how the case criteria are applied in the community.^7 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 (Table 1( so well emulates that of other published CFS cohorts.^10^,29^^\-31^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.^32 We found that low-dose hydrocortisone treatment has mild side effects (Table 3( 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.^15 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.^33^,34^



Page Synopsis: Extremely successful therapy for many patients, though it can come at a cost, for example cortisone use on a long-term basis carries significant risks. When the body registers the presence of hydrocortisone, the adrenal glands decrease production. Although proponents of low-dose hydrocortisone claim that the risks are minimal, when taken over a long period of time the adrenal glands may fail to produce glucocorticoids altogether, making the patient entirely dependent on a drug source for this essential hormone.


In addition to the risk of dependency, the dosage must not be excessive or Cushing's syndrome may eventually develop, with tendencies for obesity, hypertension, osteoporosis, and mental disturbances. Side effects of even small doses of cortisol include headache, gastrointestinal disturbances, insomnia, and weakness. Hydrocortisone is strongly contraindicated for people with fungal infections

Skill Level  3

Relevance:5 Technical Level:2


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That it can be used to avert post exertional malaisse, Low Dose Hydrocortisone is at the top of my list (see personal plan



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