• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

My understanding of treating adrenal fatigue

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
One of the problems in discussing the impact of things like corticosteroids is we are relying on highly reductionistic research. They are taking a snapshot in time and only looking at a few things. Cortisol primarily (but I think it has other functions, probably) acts by suppressing the release of arachidonic acid, if I recall correctly. Its a one pathway wonder. Arachidonic acid is processed by cyclo-oxygenase to make inflammatory hormones. The balance of those hormones determine the symptoms - and that balance depends on things like oxidative stress, cytokines and so on. The entire balance determines the outcome, not just one chemical, and this balance is constantly changing. I have heard it discussed as trying to shoot a flying bumblebee at a hundred yards, or trying to play a symphony with the metabolism and immune system without a conductor or musical score. Its complicated. Its not completely reliable.

In any case the only way to find out for most patients is to very very cautiously test something to see if it works, then to monitor to see its still working and not causing problems over time. This isn't easy either as most patients are doing many things at once - so which one is responsible for what?

There is another reason to use DHEA though - it can simulate mitochondrial replication. Since we have mitochondrial issues that could be a good thing.

Bye, Alex
 

adreno

PR activist
Messages
4,841
Agree, it depends on the persons hormonal profile before using corticosteriods. The HIV study mentioned a drop in dhea as well as increase in cortisol, so dhea may treat the negative effects of cortisol. Other studies showing dhea lowering IL6 which is a major inflammatory cytokine in cfs/me. I think this is showing what i have been saying that u need a good level of dhea before looking into increasing cortisol levels, dhea on its own maybe enough.

Yes, the HIV study supports what you have been saying about DHEA. It says in the abstract that DHEA blocks the immunoregulatory effects of cortisol. So we probably cannot look at the actions of cortisol alone, but have to look at combined effects, like Alex says.

Whether this makes it safe to take corticosteriods, I am still not sure. One problem is that "physiological" doses aren't very well defined. I have seen great variation in the ranges suggested (anywhere from 10-40mg), so it seems that there is no agreement on this.

Another problem is that the body makes constant changes in the output of varies hormones, and trying to approximate this manually is damn near impossible. It's like trying to fine tune a swiss watch with a monkey wrench.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
down stream hormones can cause problems with up stream hormones but upstream hormones like dhea and pregnenolone dont have negative feedback issues, so one can try small doses and retest hormones to see their effects down stream and adjust as needed. eg testosterone therapy can shut off dhea and pregnenolone production but the other way doesnt. I think hormones are a try and see as well as ongoing tests with dhea and preg probably safer then other hormones. I dont think prednisone etc are something people should look at lightly but for some i guess it helps after other avenues have been tried.

Adreno have u tried dhea yourself. I think your experience with trying to increase cortisol is a common problem with many cfs/me people. I got significanty worse with adrenal gland extracts, i just think there is something to dhea that can help those maybe without having to go down the cortisol line. I also think women may benefit from progesterone more so then dhea.

Its all a work in progress for everyone who go's down this line.

cheers!!!
 

adreno

PR activist
Messages
4,841
Yes, I have tried DHEA. 10mg gave me diarrhea, erection problems, and headache (I think; it's a few years back).

Let me clarify about the adrenal extracts. They actually helped me a lot at first, obliterated my fatigue and other symptoms. I felt quite wonderful for about 6 weeks. I was working full time, and standing up whole day without problems. Then from one day to the next I developed dysautonomia/OI/POTS. That's about 3 years ago, and I still struggle with that.

After that I was bedridden for a year. I then decided to try HC. Even at "physiological" doses (10-15mg) it caused skin atrophy. I also felt much more unstable, and had wild crashes. Trying to reduce the dose caused terrible crashing. I finally one morning (after not sleeping) decided not to take it any more. It was a nightmare for months.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
i initially got good results from pregnenolone which increased my cortisol and testosterone but eventually felt horrible from it, but it gave me enough positives to look into it further, same with adrenal extracts, there was something that it was doing that was helping i just had to stop what was making me feel like crap, i think i have sorted it for now. But like u have mentioned early, its not the adrenals but the hypothalamus (HPA axis) which i think is damaged in cfs/me and becomes sensitive to these hormones it is suppose to regulate.

Have u considered transdermal dhea cream as this might circumvent bowel problems?? I think we need to try and dose very low like 5mg or maybe even as low as 1mg and make increments monthly on how we feel. I dont think very low doses would have an impact on blood tests until doses get up to 20mg range.

just a thought.

cheers!!!
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
down stream hormones can cause problems with up stream hormones but upstream hormones like dhea and pregnenolone dont have negative feedback issues, so one can try small doses and retest hormones to see their effects down stream and adjust as needed. eg testosterone therapy can shut off dhea and pregnenolone production but the other way doesnt.

The problem with taking upstream hormones though is that they rarely turn into the things you want them to, especially in an already dysregulated body. DHEA tends to turn into estrogen in me. I know you are taking arimdex for this issue, but arimidex just made me feel bad. I started off like you, took cortisol, felt horrible, so then took dhea. Oral version didn't agree with me at all. Transdermal worked better, but too much conversion to estrogen. Took small dose of arimidex, felt horrible.

Basically my pattern with hormones (and indeed other drugs) is when I take something which has major unwanted effects, taking something else to try and counter those unwanted effects doesn't work and just makes the whole system even more unstable.

I got significanty worse with adrenal gland extracts, i just think there is something to dhea that can help those maybe without having to go down the cortisol line.

I definitely agree with your main point on this thread that we need adequate levels of androgen before we can tolerate cortisol (very few hormone specialists even acknowledge this basic fact, I think Thierry Hertoghe is one of the few). However I'd also say that adequate levels of androgen are necessary but not sufficient to tolerate cortisol.
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
Agree, it depends on the persons hormonal profile before using corticosteriods. The HIV study mentioned a drop in dhea as well as increase in cortisol, so dhea may treat the negative effects of cortisol. Other studies showing dhea lowering IL6 which is a major inflammatory cytokine in cfs/me. I think this is showing what i have been saying that u need a good level of dhea before looking into increasing cortisol levels, dhea on its own maybe enough.

I think adrogens are necessary to tolerate cortisol, but not sufficient. At least in my case adding dhea or armidex didn't work.

I agree with you that on paper dhea is a fantastic hormone (e.g. see links below), the problem is I just couldn't find a way to get it to work for me.

http://www.lef.org/LEFCMS/aspx/PrintVersionMagic.aspx?CmsID=34880

http://www.bio.net/bionet/mm/bioforum/1999-January/028260.html
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
dhea in me did aromatise to E2 in me and arimidex(1/2mg twice a week) controlled this, i wasnt really after testosterone increases although would be nice but was chasing dhea's immune improvements and also its effects on cytokines to help improve sleep which i think it has. Also i have been carrying extra weight which also increases aromatisation, lowering E2 can help with weight loss and with my low carb diet, improving insulin sensitivity i have lost a good amount of weight. so lowering body fat can help lower E2. I have been having symptoms of low E2 of late ie increased muscle pains and joint stiffness, a recent blood test confirmed my E2 was too low, so i think losing the weight has helped lower my E2 and possibly now can lower or come off arimidex. My E2 was high before dhea but now on dhea(25mg) my E2 like i mentioned is now low and i think/hope will remain within a good level while remaining on dhea. So i think i can maintain good estrogen levels within normal range and have my weight under control, so arimidex may not have to be used forever.

Im not advising anyone to do what i have done but just an example that it can get complicated and many things need to keep being adjusted and retested. Also that up stream hormones have other effects then just topping up down stream hormones i have found, at the moment dhea is doing little to my testosterone and estrogen but feeling better on it??

Garcia, there are other anti-estrogens worth trying, aromasin is one that comes to mind and have read from other guys who have had less sides from this then arimidex. Also nolvadex blocks estrogen from working and can help increase testosterone secretion as well as clomid, i think nolvadex has to be tapered off to maintain results. I think many guys have hormonal problems due to being a fatty(can be a horse or the cart thing as well as its hard to maintain weight with cfs), i think with extra help with some of these anti estrogen/ anti aromatisation meds and a good diet we can lose weight and this can help change our hormonal profile permanently and then come off meds and as long as a healthy weight is maintained we should keep good hormones, easier said then done, but im having a go!

I also dont think this is the golden goose, with cfs/me we need to marry this with infection/immune treatments.

cheers!!!
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Even at "physiological" doses (10-15mg) it caused skin atrophy. I also felt much more unstable, and had wild crashes. Trying to reduce the dose caused terrible crashing. I finally one morning (after not sleeping) decided not to take it any more. It was a nightmare for months.

I can only imagine! For most men, a physiological dose is much higher than that (think more in the range of 30-40 mg a day in divided doses if your adrenals were completely shot). Less than that could have easily produced the most horrible feeling adrenaline surges and would likely have felt like a roller coaster from hell. Most doctors don't recommend "ramping" up dosage any more for exactly that reason and prefer to start patients on what is an appropriate full dose for them.

Sometimes taking cortisol does also cause aldosterone to lower. This happened to me a few months after starting HC. I had aldosterone tested due to low electrolyte labs and then started Florinef and the dizziness and OI has now almost completely gone. It used to be a terrible problem and I am grateful for Florinef every time I stand up!

Re skin atrophy - were you using a HC cream or pills? I have seen a few people have trouble with thinning skin using the cream but never an issue once they switched to tablets.

It sounds like you didn't really have much guidance on dosing through the process or instruction on how to find the minimum effective dose of HC that would alleviate your symptoms without causing side effects. I hope that you are feeling better though now regardless.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Ema, I used tablets.

Do you have any references to your claim that men produce 30-40mg per day?

This study found daily production rate to be 9.9 +/- 2.7mg:

http://www.ncbi.nlm.nih.gov/m/pubmed/1986026/

It's a clinical judgment based on my own experience and that of doctors and other practitioners I've worked with that are familiar with cortisol and how to use it and other steroids successfully. I have seen 40 mg as the upper physiological limit in some written reference materials but mostly doctors speak in hushed tones around steroid usage and dosages because of all the stigma and fear.

And the truly ignorant doctors seem to think that 20 mg is sufficient however as mentioned before, concurrent bacterial and viral infections that are so common in ME/CFS increase our steroid needs above that of the general population and often cause a need for more frequent dosing as opposed to the typical Addison's patient that may do very well on a lower dose taken two or three times a day.

I honestly wish there were better studies and published protocols because I know that this "leg of the table" could make such a difference to so many people suffering with HPA dysfunction. However, it often all goes pear shaped and the steroids are blamed instead of the dosage and process.

I also agree with what Alex wrote above.
 

adreno

PR activist
Messages
4,841
Ema, I assume you are aware that studies have found very little improvement with HC, and that at 30-40mg you risk suppressing endogenous cortisol production? When comparing risks and benefits, I find it simply not worth it.


Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial.

McKenzie R, et al.

JAMA. 1998 Sep 23-30;280(12):1061-6.

Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1888, USA.

Abstract

CONTEXT: Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic-pituitary adrenal axis and hypocortisolemia.

OBJECTIVE: To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS.

DESIGN: A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996.

SETTING: A single-center study in a tertiary care research institution.

PATIENTS: A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications.

INTERVENTION: Oral hydrocortisone, 13 mg/m2 of body surface area every morning and 3 mg/m2 every afternoon, or placebo, for approximately 12 weeks.

MAIN OUTCOME MEASURES: A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist.

RESULTS: 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.

PMID 9757853
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
I think we will just have to agree to disagree.

I think the studies are in many cases flawed and contain too many other variables to make sweeping generalizations about anything much less the appropriate type,dose and protocol of steroid for conditions that are barely understood at all themselves.

I see people get better with physiological dosing of steroids every single day and hate for people to be misled and fearful based on antiquated information and flawed studies. As I said, I do wish there were more in the way of perfect studies but the lack of them is not a convincing reason for me to not use a treatment that shows great benefit to many who have a disrupted HPA axis. It is not the entire picture but it is a vital piece in my opinion.

I hope Rich is right though and that removing the methylation block will allow hormones to come back up...but in the meanwhile, I will continue to supplement the missing end hormones and enjoy no longer being bed bound with debilitating OI.
 

maddietod

Senior Member
Messages
2,859
I took hydrocortisone, as Cortef, maybe 10 years ago, for about 2 years. I took 2.5mg on waking and at lunchtime. It pretty much "fixed" me, which was fabulous until I started worrying about the requirement for 2ce yearly liver function tests. I weaned myself off it very very slowly, and got unfixed, but I also didn't do any damage to myself.

This is why I've always assumed that my problem involves the adrenal glands.

Very recently, my hybrid methylation protocol seems to be getting results; I've had to reduce my adrenal supports. So it's looking like proper methylation is normalizing my hormones.
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
I see people get better with physiological dosing of steroids every single day and hate for people to be misled and fearful based on antiquated information and flawed studies. As I said, I do wish there were more in the way of perfect studies but the lack of them is not a convincing reason for me to not use a treatment that shows great benefit to many who have a disrupted HPA axis. It is not the entire picture but it is a vital piece in my opinion.

I wonder how many of those people have full-blown neurological ME? I've seen too many people get really screwed up from hydrocortisone, only to be told that they need to "optimize", i.e. go higher with the dose, only for their symptoms to get worse and worse. I myself did really badly on corticosteroids. They completely shut down my immune system at all doses. Yet there are still people out there who keep pushing the line that "physiological" doses of steroids are not harmful. They may not be for some people, but they are for others. I think people should be allowed to try them (under medical supervision), but they should also be warned of the risks and that those risks are not just based on flawed studies, but actual patients who have suffered relapses (even with low physiological doses).
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
Natural killer cells: These cells are very important in killing viruses and bacteria. It is very difficult to eradicate chronic infections when these cells are not functioning well. Antibiotics and antivirals do not work well and are often infective if the immune system is not stimulated as well. You are never able to kill all the infectious agents unless the body is able to clean up the residual left by the antibiotic or antiviral.

There are a number of methods to do this. What we use depends on the infection present, but includes both natural and pharmaceutical antivirals, antibiotics, immune boosters and immune modulators. Growth hormone, thyroid and cortisol (adrenal hormone) are also very good immune enhancers. Yes, I said cortisol - low doses of cortisol for people who have adrenal insufficiency act as an immune enhancer. Large doses are immune suppressors. Your body normally increases cortisol in times of infection. Oxidative therapies, discussed below, can be very powerful. We customize the specific treatment for the patient.

http://www.hormoneandlongevitycenter.com/cfidsfibromyalgia/#12

There is another article i printed out a while ago(cant find the exact link) explaining hydrocortisone use in cfs/me helps immune function and the doses used 5-15mg in several studies werent supressive. I dont think this treatment is for everyone but if one hasnt tried it, i think its worth looking into, the artilce was by holtorff with references to these studies .

cheers!!!
 

adreno

PR activist
Messages
4,841
One doctor's opinion is not evidence of anything. I saw no references in the link you provided. People can claim anything, but without references, we should be very careful in trusting those claims.

Here are three studies showing that cortisol inhibits NK cells.

Inhibition by cortisol of human natural killer (NK) cell activity.
http://www.ncbi.nlm.nih.gov/m/pubmed/2434732/

Cortisol at physiological concentrations and prostaglandin E2 are additive inhibitors of human natural killer cell activity.
http://www.ncbi.nlm.nih.gov/m/pubmed/2423476/

Hormone specific regulation of natural killer cells by cortisol. Direct inactivation of the cytotoxic function of cloned human NK cells without an effect on cellular proliferation.
http://www.ncbi.nlm.nih.gov/m/pubmed/2065773/

But I suspect this is a pointless exercise, as any data I present is dismissed as "flawed studies".

I am still waiting to see a single piece of evidence to support the claims of HC therapy proponents in this thread.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
One doctor's opinion is not evidence of anything. I saw no references in the link you provided. People can claim anything, but without references, we should be very careful in trusting those claims.

Here are three studies showing that cortisol inhibits NK cells.

Inhibition by cortisol of human natural killer (NK) cell activity.
http://www.ncbi.nlm.nih.gov/m/pubmed/2434732/

Cortisol at physiological concentrations and prostaglandin E2 are additive inhibitors of human natural killer cell activity.
http://www.ncbi.nlm.nih.gov/m/pubmed/2423476/

Hormone specific regulation of natural killer cells by cortisol. Direct inactivation of the cytotoxic function of cloned human NK cells without an effect on cellular proliferation.
http://www.ncbi.nlm.nih.gov/m/pubmed/2065773/

But I suspect this is a pointless exercise, as any data I present is dismissed as "flawed studies".

I am still waiting to see a single piece of evidence to support the claims of HC therapy proponents in this thread.

A doctors personal experience means alot, we would be crazy not to take this into consideration, most cfs/me treatments are based on dr's experience not research, if anything its a stepping stone to further research. I will try and find the links to studies done which i have seen before, what i posted didnt have links.

This doctor has seen nk function improve on those with low cortisol levels, because its not in a study doesnt mean it didnt happen.

Could also say the pace trial is effective treatment for me/cfs because there is a study on it also.

I just dont think its an issue to be close minded on and that for some it has helped, because one has had a negative experience doesnt mean everyone will have that same experience. I dont think its hard to believe that low cortisol could cause immune suppression, if it didnt then drugs to lower cortisol would be used for immune defiencies.

cheers!!!
 

adreno

PR activist
Messages
4,841
I dont think its hard to believe that low cortisol could cause immune suppression, if it didnt then drugs to lower cortisol would be used for immune defiencies.

And this is exactly what is happening; glucocorticoid antagonists are being employed in HIV:

"By utilizing the interaction between Vpr and the glucocortoicoid receptor, glucocorticoid antagonists such as mifepristone hold promise for anti-retroviral therapy by both preventing viral transactivation in currently-infected cell populations as well as preventing the reactivation of latent virus."

http://d-scholarship.pitt.edu/8701/
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
Heres one from simon wessely showing cortisol helps with minor side effects, 5-10mg a day dose used, http://www.kcl.ac.uk/content/1/c6/01/47/68/HydrocortisoneinCFS.pdf

http://www.ncbi.nlm.nih.gov/pubmed/11502777

This is a horse study so not human http://www.ncbi.nlm.nih.gov/pubmed/21430601
Low-dose hydrocortisone (LDHC) therapy modulates inflammatory responses in adults and improves outcomes in some septic adults and neonates, but its immunologic effects have not been evaluated in neonates. The objective of this study was to evaluate effects of LDHC therapy on ex vivo immune function in neonatal horses (foals). We hypothesized that LDHC treatment would dampen proinflammatory responses without impairing neutrophil function. Hydrocortisone (1.3 mg/kg/d i.v.) was administered to foals in a tapering 3.5 d course. Peripheral blood leukocytes were collected from foals before, during, and after hydrocortisone treatment. A separate group of age-matched untreated foals served as controls. Endotoxin-induced peripheral blood mononuclear cell gene expression of inflammatory cytokines was measured by real-time quantitative RT-PCR. Neutrophils were incubated with labeled, killed Staphylococcus aureus or Escherichia coli for assessment of phagocytosis, and with phorbol myristate acetate, zymosan, or endotoxin for measurement of reactive oxygen species (ROS) production. Neutrophil phagocytosis and ROS production were similar in both groups. Foals receiving hydrocortisone had significantly decreased endotoxin-induced expression of TNF-?, IL-6, IL-8, and IL-1?. These data suggest that this LDHC treatment regimen ameliorates endotoxin-induced proinflammatory cytokine expression in neonatal foals without impairing innate immune responses needed to combat bacterial infection.

Just a few i found with a quick google.