Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Adrenal fatigue really just HPA-axis downregulation?

Discussion in 'General Treatment' started by NotThisGuy, Mar 31, 2017.

  1. NotThisGuy

    NotThisGuy Senior Member

    I think my whole live i have trouble with my adrenals. Maybe it was because of chronic infections like fungus and borrelia, maybe genetics or maybe something else.
    10 years ago i was diagnosed with IBS-D.

    Since 1 year my adrenals are a true mess now and i developed CFS.
    I read a lot about adrenal fatigue theories and how to treat it and lot of people came to the conlcusion that the adrenal fatigue theory is false and it's just a downregulation of the HPA-axis.

    I tried to find a way to boost this axis and tried all the common herbs recommended for upregulation of the HPA-axis. Nothing worked so far.

    I found this interesting study among a lot of others that came to the conclusion, that methionine and leucin boosts the HPA-axis:

    "These results indicate that both met- and leu-enkephalin increase the activity of the HPA axis in rats and both central opioid and adrenergic alpha-receptors are involved in this stimulation."

    (How do i mage this look like an quote window?)

    Another study says, that methionine and leucin increased corticosterone but not ACTH. corticosterone&source=bl&ots=7ziHrXuUMM&sig=WRchDwXbeHSY3ARFMnCgVdSepAo&hl=de&sa=X&ved=0ahUKEwiIpqPdw_HSAhXKhiwKHR9pD3w4ChDoAQheMAg#v=onepage&q=leucine corticosterone&f=false

    There are more studies regarding leucin and methionine and corticosterone and HPA-axis.

    Both methionine and leucin is doing something.
    I have a salt intolerance and my adrenals are so weak by now that i have constant fear my heart is stopping anytime soon. I also developed POTS and orthostatic dyspnea.(to this point where I was gasping for air like a fish, really scary)
    Leucin and methionine both give my a little craving for salt, but i still am really thirsty and cant tolerate sodium.
    Leucin and methionine reduced my PEM.
    Allthough methionine worsened my dyspnea a bit.
    I only tried micro-doses of both. (Maybe 1mg of each, maybe less)
    The dyspnea gets better after some licorice. Maybe cortisol depended dyspnea?

    Right now im asking myself, what if it's not just a downregulation of the HPA-axis? What of we truely are way too deficient in nutrients, so the adrenals just can't produce the hormones? (@Freddd's refeeding syndrome)
    This theory shouldn't be big news to everyone since a lot of people support this theory.

    I tried vit. B5 for 1-2 months and it truely gave me a boost before i crashed. So maybe whatever pathway uses B5 to produce adrenal hormones just got way to deficient in other nutrients? but which nutrients?
    Im specifically interested in those pathways that includes the renine-angiotensine-system.
    My renine is way to high so the problem can't be there.
    My ACE (angiotensin-converting-enzyme) is low and my angiotensin II is also low.

    Since @Lolinda stated that POTS gets better with acetylcholine the next thing to try might be serine, which is necessary for acetylcholine production.

    Anyone here with adrenal fatigue and POTS or hypotonic problems who has a blood panel /urine panel of aminoacids?
    Since i tried every vitamin possible the problem might be deficient aminoacids
    Last edited: Mar 31, 2017
  2. caledonia


    Cincinnati, OH, USA
    Treating adrenals can be tough. There seems to be two types - one where the adrenals themselves are fatigued and get better with support like adrenal cortex extract. Another one where hypothalamus and pituitary signaling aren't working correctly, so the adrenals don't work right. Rich Van Konynenburg hypothesized that this was due to glutathione depletion. In this second case, the adrenals themselves are fine and ACE is too stimulating.

    Mine is like the second case. For management, I replace the electrolytes which are leaking out (potassium, magnesium, sodium). I'm also working on chelating out mercury which I believe is the root cause for my adrenal fatigue. I've tried to raise glutathione by various methods, but so far, haven't been successful. Getting rid of the mercury should allow glutathione to function correctly.

    Can you explain more about salt intolerance? Do you mean it causes high blood pressure? I've never heard of anybody actually allergic to salt, although I could see being allergic to additives put in it.
    CedarHome likes this.
  3. NotThisGuy

    NotThisGuy Senior Member

    It's no allergy to salt.
    My thirst increases when I take the tiniest bit of salt, also my blood pressure is going down. said with low aldosterone salt intake depletes even more aldosterone, so i think thats the problem.

    I currently don't know which case I am, maybe both?
    I really cant take any electrolytes.
    Sodium gives me aldosterone depletion symptoms, potassium and magnesium gives me overdose symptoms.
    Magnesium is quite high in a blood test, potassium isn't tested yet.

    Edit: phosphorus and chloride increas thirst, too
    keenly likes this.
  4. NotThisGuy

    NotThisGuy Senior Member


    I suspect I have also problems with mercury.
    I also have heavy polyuria, sometimes I have to drink 6-9 liters a day.
    Do you have any experience with desmopressin?
    I also have heavy gut problems like SIBO and leaky gut confirmed by tests.
    I guess the 4R-programm is the way to go. I've read you guides but I'm still puzzled how to fix my gut. I'm working on it, but I have trouble with the remove-phase. So far pancreatine seems to work. Only taking micro-dosis but working my way up.
    Do you have any experience with candibactin or the SIBO-protocol by Rostenberg?
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

    australia (brisbane)

    Many dont realise that with adrenal dysfunction that aldosterone even exists and they concentrate on cortisol and dhea. Cortisol and dhea were low for me but i have sorted with supps. Urination was 10litres a day, now on desmopressin which helps alot especially with sleep as i didnt realise how much it woke me up at night. A side effect of desmopressin is that sodium can drop too low which happened with me so i use electrolytes or salt tablets regularly. Desmopressin i take at night but only in the morning if working or something else on, hopefully help avoid low sodium levels. Hard to explain why sodium drops as u would think the opposite but if u look it up its easier to understand.
    bertiedog likes this.
  6. caledonia


    Cincinnati, OH, USA
    Sorry I don't have experience with the various substances you mentioned.

    I know someone who worked with Rostenberg on their gut. There was a strict elimination diet for a couple of months, and a bunch of supplements. It sounded expensive. Fixing the gut was supposed to help his mental health, but it didn't work. He's finally found relief with ketamine infusions.

    Mercury toxicity can cause pyroluria, and adrenal fatigue. I'm doing the Cutler protocol for mercury chelatoin. Cutler has a lot of suggestions for helping the gut, adrenals, pyroluria, etc. while you're working on chelation. Getting the mercury out would be the ultimate fix.

    In the meantime, you can try the Core Four supplements - vitamin C, vitamin E, zinc, and magnesium.

    See my signature link on Cutler chelation for a link to a synopsis of the protocol, the exact forms and amounts of supplements, etc.
  7. NotThisGuy

    NotThisGuy Senior Member

    Thanks for your suggestions.
    Unfortunatly i don't tolerate any supplements anymore.
    Vit. C&E lowers my blood pressure and blood flow too much. Zinc makes me anemic and copper isn't well tolerated either (dyspnea and brain fog). Magnesium makes me thirsty and I'm already on the high side.
    I'm down to 4 foods since over 1 year now.
    Dr. doesn't want to do any chelation because she thinks that would kill me.
    I'm very low on alpha-lipoic also. I think my biggest problem is low ATP due low alpha-lipoic acid.
    I'm really scared to start alpha-lipoic acid because I had very bad experience with the lowest amount of selenium. (Anxiety,OCD & heart problems increased drastic)
    It's really hopeless isn't it?
  8. charles shepherd

    charles shepherd Senior Member

    MEA notes on adrenal gland function, adrenal gland testing, and the use of steroids as a possible form of treatment for ME/CFS:

    1 Although there is consistent research evidence to show that part of the underlying disease process in ME/CFS involves what is called the hypothalamic-pituitary-adrenal gland axis, and that this can cause a reduced output of the hormone cortisol from the two adrenal glands (ie hypocortisolaemia) which sit above the kidneys, there is no evidence from clinical trials to indicate that steroids are a safe and effective form of treatment.

    2 Testing the function of the adrenal glands should be done through a GP (in the first instance) by checking the blood level of cortisol at 9am. If this is low, then further testing of adrenal gland function in the form of what is called a synacthen test might be necessary - this is a dynamic test that is done in hospital and involves giving a hormone (ACTH) that stimulates the adrenal glands to produce cortisol.

    3 I would not recommend the use of tests that are sometimes arranged by alternative health practitioners, including just checking one off measurements of salivary cortisol

    If testing for adrenal insufficiency needs to be done this should always be arranged on the NHS.

    4 Although some minor benefits from the use of low dose steroids have been reported in ME/CFS, the current consensus is that the disadvantages (including further suppression of the natural output of cortisol from the adrenal glands) of using low dose (or even high dose) steroid treatment in ME/CFS outweighs any possible benefit.

    5 Research into HPA dysfunction and low levels of cortisol is summarised and referenced in the Research section of the MEA purple booklet:

    MEA purple booklet:

    6 Clinical trials involving steroid treatment in ME/CFS are summarised and referenced in the Treatment (Immunological section) of the MEA purple book


    Information from the MEA purple book (2016 edition) on the assessment of hypocortisolaemia (low cortisol levels) and cases where Addison's disease (severe cortisol deficiency) needs to be excluded:

    Arrange a short synacthen (ACTH) test if plasma or urinary cortisol is low with symptoms (i.e. weight loss, nausea, pigmentation of non-sun exposed areas) and if routine screening tests suggest Addison’s disease (i.e. hypotension, low serum sodium, raised potassium).

    The short synacthen test may fail to identify people with ACTH deficiency due to hypothalamic or pituitary disorders.

    The insulin tolerance test remains the gold standard for diagnosing ACTH deficiency, with the other tests in reserve and to be interpreted in the light of clinical context.

    The basal 9am cortisol is also of contributory value.

    Cortisol is secreted in a pulsatile manner and has a diurnal variation (a peak in the morning and a trough at night) so measuring cortisol at random gives a poor indication of adrenal function in most cases.

    Cortisol measured at 9am can be used as a crude indicator.

    A measurement of > 500nmol/l suggests normal adrenal function and a measurement of < 165nmol/l suggests adrenal insufficiency.

    A measurement of < 100nmol/l at 9am is diagnostic of significant deficiency and requires urgent referral.

    Dr Charles Shepherd

    Hon Medical Adviser, MEA
    NotThisGuy and GreyOwl like this.
  9. NotThisGuy

    NotThisGuy Senior Member

    Thank you very much shepherd.
    I'm seeing an endocrinologist and he suggested the use of florinef and cortisol.
    Might rethink the use of cortisol now....

    Right know I think I've maybe depleted my copper over the years.
    First of all I found one case where someone got copper deficient due too much softdrinks.
    I drank 1 liter coke every day for 5 years.
    I also took a lot of copper chelating supplements.

    I also found a study that said copper is necessary for adrenal hormones and serum copper increases aldosterone.
    So right know i handle the brainfog with lemonjuice and salt (lemonjuice for potassium). I can not take sodium or potassium without copper.

    At first I thought i react to copper this strange because I have high biounavailable copper, but I get the same reactions when I take leucin or methionine (allthough methionine gives me copper deficiency symptoms after few hourse).
    When i tried little adrenal cortex extract I had the same reaction. That's why I'm pretty sure it's just the reaction to adrenal hormones and not copper itself. Freddd also said he got low testosterone while he was copper deficient. My test show the same result.

    Tests also showed I'm low on zinc (supplemented for 1 year with 25mg) and molybdenum.
    My uric acid is also very low maybe because of low molybdenum.
    I think it's pretty hard to find the right balance between zinc, copper and molybdenum for the beginning. I think at first this can't be done without taking some florinef or adrenal cortex extract and rebalancing potassium and sodium which got depleted.
    The gut is still a mystery......
  10. NotThisGuy

    NotThisGuy Senior Member

    It makes sense that people with CFS are more likely to have higher MSH. Here’s why:

    • MSH causes flushing, lower blood pressure and increased pain (R), all common symptoms of CFS.
    • Stress increases the likelihood of CFS and the intensity of symptoms (R). Stress increases MSH.
    • People with CFS are more likely to be thin, and a-MSH causes weight loss.
    • People with CFS are more likely to have intestinal inflammation, which increases MSH.
    • People with CFS are more likely to have anxiety and depression, which can both be caused by MSH.
    • MSH suppresses orexin in animal models (R), which may theoretically lead to fatigue.
    Indeed it’s the case that in 55 people with CFS, a-MSH levels were higher than healthy controls.

    The stress-induced increase in α-MSH probably originates from the pituitary gland [R].

    CFS and “Pituitary Fatigue”
    In CFS, there may be a disorder of the hypothalamic dopaminergic neurons, and that this could further affect pituitary hormone secretion. Although the structure of the intermediate lobe is less clear than that seen in rodents,

    As time went on in people with CFS, their a-MSH declined. This may be a result of a dysfunction of the pituitary cells that release a-MSH (melanotrophs) because of prolonged stimulation by stress. In a rat model, melanotrophs subjected to continuous stress for more than 5 days showed degenerative features due to hypersecretion of α-MSH, and the raised a-MSH levels fell five days after stimulation [R].

    Thus, melanotrophs in humans with CFS are likely to become exhausted and impaired by prolonged stress. It is also possible that the melanotrophs become desensitized following prolonged stimulation, or that the prolonged high level of a-MSH may activate an unidentified feedback system from the periphery.

    Hence, people with CFS may have “Pituitary Fatigue.”

    Thats pretty much a match for me.
    Thin, low blood pressure, anxiety, depression.

    Anyone here have there MSH levels tested, or know a way (not just the ones this site mentions) hot to decrease it?
    Or are we supposed to raise it?

    I always noticed that my "adrenal fatigue" is pretty much gone when my dopamine raises.
    Last edited: Jun 30, 2017

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