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Lessons from ME/CFS: Finding Meaning in the Suffering
If you're aware of my previous articles here at Phoenix Rising then it's pretty clear that I don't generally spend my time musing upon the philosophy of the disease. I find it better to spend my time reading research and trying my best to break it down to its core elements and write...
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A defect in cortisol production in rheumatoid arthritis: why are we still looking?

Discussion in 'Other Health News and Research' started by Snow Leopard, Oct 12, 2012.

  1. Snow Leopard

    Snow Leopard Senior Member

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    I have always had a nagging feeling that the (mixed) findings related to the HPA axis in CFS patients was a red herring, but I didn't understand why I felt this way. It is clear much of our understanding of how this relates to disease is probably wrong.

    The similar same observations have been found in other disease cohorts, particularly in Rheumatoid Arthritis patients and I found this 2005 article interesting:
    "A defect in cortisol production in rheumatoid arthritis: why are we still looking?"
    http://rheumatology.oxfordjournals.org/content/44/9/1097.full

    If the HPA axis is in dynamic equilibrium with the immune system and a strong stress response suppresses the immune system, then the opposite effect would be that an activated immune system would suppress the HPA axis. This may explain the findings in RA, CFS patients as well as other groups.

    Additionally, certain people like to suggest that most/all CFS patients are subject to chronic stress and this is somehow a maintaining factor. While some patients are living under stressful conditions (eg struggling in terms of finances, relationship issues and social isolation), this is not true of all patients and therefore cannot be used to explain the findings in many patients. The fact that patients are apparently experiencing high stress, yet not mounting a classic physiological stress response is never explained.

    In fact the idea that "stress" is always bad appears to be a half-truth at best. Indeed in rat models, some stress has been shown to lead to increased resistance to the development of autoimmune conditions.
    "Stress in autoimmune disease models."
    http://www.ncbi.nlm.nih.gov/pubmed/16855134
    RosieBee, penny, xrayspex and 3 others like this.
  2. Snow Leopard

    Snow Leopard Senior Member

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    Here is a more recent (and comprehensive) review of the stress responses in RA patients:
    Experimental stress in inflammatory rheumatic diseases: a review of psychophysiological stress responses
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911873/

    It has a neat table, there was actually minmal/no effect on many cytokines (with the possible exception of TNF-alpha), though the article ends with the classic 'stress is bad' type conclusion.
    L'engle likes this.
  3. Esther12

    Esther12 Senior Member

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    Ta SL.

    I've been meaning to look in to HPA findings across a range of conditions, but have never really done much on it.

    It does seem strange that the CFS HPA findings are viewed as so significant by some, when it seems entirely possible that these are a secondary to a range of illnesses. It would be good to do a study on people with suspected CFS - if 50% of cases tend to have alternative diagnoses, testing before they were sorted out could help minimise confounding factors.

    While there can be problems with defining and measuring 'stress', I think that there probably is a fair definition for which we can safely assume that CFS patients have more of it than those without health problems. Indeed, the uncertainty and quackery around CFS can make it particularly 'stressful'. There are still going to be lots of fortunate CFS patients with relatively low levels of stress, and lots of healthy people with other stressful problems or difficulties with anxiety... but having CFS is a bit rubbish, and this in itself is a 'stress'.
  4. justy

    justy Senior Member

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    For me, one of the main issues with stress and M.E, is not that stress makes me more ill, or that i have more stress, but simply that my body seems unable to cope any longer with normal everyday stresses. Havent read the links yet - just thought i would chip in in general about stress.
  5. nanonug

    nanonug Senior Member

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    I was going to say something like this but you were faster and pithier than I probably would be.
    RosieBee likes this.
  6. Sing

    Sing Senior Member

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    I lost a normal fight or flight capacity years ago, instead just going into exhaustion. My energy capacity or budget for stress of all kinds is minimal. This includes the fun stuff too, not just the unpleasant, frightening, negative forms of stress. And of course, not just emotional stress but every sort of physical stress. Speed and intensity I can't afford.

    Because I got on cortisol years ago too, twice a day, this pulls me out of the sore throat, flu symptoms and need to lie down that my days used to revolve around. But cortisol is not adrenaline and does not replace a low functioning HPA axis. It helps but is only one part.
    RosieBee likes this.
  7. beaverfury

    beaverfury beaverfury

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    Ditto. I have lost any sort of robustness in my approach to life.

    I cant deal with the things i used to because my stress response is so sensitive. I live my life like a timid wallaby.
    Its not the external factors but my new HEIGHTENED RESPONSE to them.

    Ive lost patience with my own piss poor AMATEUR net research. Let me revert to naive child mode- Why is it so hard to determine whether HPA axis dysfunction is primary or secondary??

    I know theres little place for heuristics in science, but they seem to do experiment after experiment, for years WITHOUT COMING TO ANY FREAKIN CONCLUSIONS! Sometimes i wish Chopper Read was a scientist.
    Chopper would sort this sh*t out!
  8. beaverfury

    beaverfury beaverfury

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    Apologies. I'm not really aggressive:D. Just frustrated

    LOVE, everybody:hug:
  9. Snow Leopard

    Snow Leopard Senior Member

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    LOL

    Anyway, I strongly feel it is secondary, I would bet money on it.
    natasa778 likes this.
  10. beaverfury

    beaverfury beaverfury

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    Ah, i like it! At least you have leapt in! Just like Chopper!

    I would bet on it being primary. Whilst acknowledging that im just trying to win money on my own ignorance.

    Lets hand the problem over to SONY or APPLE. They would solve it in a month!
    Sing and jace like this.
  11. beaverfury

    beaverfury beaverfury

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    I know next to nothing about algorithms and heuristics, but could some smart cookie could come up with a such a model for HPA axis involvement in me/cfs? Since science is failing us

    I know its a revolving circle of inputs, but some things cant go backwards. For instance, no one would accuse the heart of being a primary cause in cfs. Something upstream has caused heart dysfunction. eg. HPA axis.

    As you made finer and finer distinctions, ie TNF-alpha produced downstream from macrophages in the presence of....
    bla bla.. you could by the trial and error of punching in millions of bits of information, come up with some model?
    Hell, the antivirus system on my computer juggles thousands of bits of information every second.
    It must be susceptible to analysis this way?

    Just wonderin. I cant do it. Im battling to make a sandwhich
    Sing likes this.
  12. currer

    currer Senior Member

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    Secondly, if a defect in HPA axis activity is subsequent to the development of inflammation, can this information lead to improved pharmacogenetics

    If the HPA axis is in dynamic equilibrium with the immune system and a strong stress response suppresses the immune system, then the opposite effect would be that an activated immune system would suppress the HPA axis. This may explain the findings in RA, CFS patients as well as other groups

    This is a really interesting suggestion snow leopard. Do you have any evidence from the medical literature that this could be so? The article you quote only states the above - (in blue)

    But such an action could be a link between autoimmunity and the HPA axis.
    xrayspex likes this.
  13. currer

    currer Senior Member

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    http://edrv.endojournals.org/content/14/5/539.short
    Immunoendocrine Communication via the Hypothalamo-Pituitary-Adrenal Axis in Autoimmune Diseases

    THE interrelationship between the neuroendocrine and the immune systems has long been a neglected subject of study.......
    .......and also on the immunoendocrine dialogue via the hypothalamo-pituitary-adrenal (HPA) axis (8). The potential modulatory role of this feedback regulation in the pathogenesis of autoimmune disease has only been suggested recently (9–13). It is the aim of this review to summarize and discuss the present state of knowledge of alterations of the immunoendocrine circuit along the HPA axis in various autoimmune diseases in experimental animals and man.
    xrayspex likes this.
  14. currer

    currer Senior Member

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    Physiology of the hypothalamic-pituitary-adrenal axis in health and dysregulation in psychiatric and autoimmune disorders.

    Tsigos C, Chrousos GP.
    Source

    Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland.
    Abstract

    The HPA axis is the principal effector of the generalized stress response and crucial for maintaining basal and stress-related homeostasis. There has been an exponential increase in knowledge regarding the interactions among the elements of the HPA axis (CRH, AVP, ACTH, glucocorticoids) and between the HPA axis and the other components of the stress system (locus ceruleus/norepinephrine-sympathetic systems), as well as with the axes responsible for reproduction, growth, and immunity. This new knowledge has allowed association of HPA axis dysfunction, characterized by sustained hyperactivity or hypoactivity, to various pathophysiologic states that cut across the traditional boundaries of medical disciplines. These include a range of psychiatric, endocrine, and inflammatory disorders or susceptibility to such disorders.
  15. currer

    currer Senior Member

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    Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases.

    Wick G, Sgonc R, Lechner O.
    Source

    Institute for General and Experimental Pathology, University of Innsbruck, Medical School, Austria.
    Abstract

    According to our concept, the development of autoimmune disease depends on the presence of two sets of essential genes, one coding for an abnormal autoreactivity of the immune system, the other for a primary susceptibility of the target organ/structure for the immune attack. The final outcome of the disease in a given individual is then fine tuned by modulatory factors, such as diet or hormones. With regard to the latter, the immuno-endocrine interaction via the hypothalamo-pituitary-adrenal (HPA) axis has proven to be of special importance. Investigating the so-called Obese strain (OS) of chickens, an animal model with a spontaneously occurring Hashimoto-like autoimmune thyroiditis, we have first shown an impaired surge of glucocorticoid hormones after stimulation of the HPA axis by antigens or certain cytokines (glucocorticoid-increasing factors--GIFs). More recently, we have found a similar behavior in models with systemic autoimmune diseases, that is, murine lupus erythematosus and avian scleroderma. More detailed studies have, however, proven that the mechanisms underlying this altered immuno-endocrine communication via the HPA axis differs in different models. Finally, recent data point to the possibility that the classical pathways of glucocorticoid-T-cell interactions also take place in the thymus itself, which has been shown to be a site of steroid hormone production.
    RosieBee, August59 and Snow Leopard like this.
  16. beaverfury

    beaverfury beaverfury

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    From the same journal:
    http://endo.endojournals.org/content/152/12/4496.abstract
    Minireview: Stress-Related Psychiatric Disorders with Low Cortisol Levels: A Metabolic Hypothesis

    Several stress-associated neuropsychiatric disorders, notably posttraumatic stress disorder and chronic pain and fatigue syndromes, paradoxically exhibit somewhat low plasma levels of the stress hormone cortisol. The effects appear greatest in those initially traumatized in early life, implying a degree of developmental programming, perhaps of both lower cortisol and vulnerability to psychopathology. In these conditions, lowered cortisol is not due to any adrenal or pituitary insufficiency. Instead, two processes appear involved. First, there is increased target cell sensitivity to glucocorticoid action, notably negative feedback upon the hypothalamic-pituitary-adrenal (stress) axis. Altered density of the glucocorticoid receptor is inferred, squaring with much preclinical data showing early life challenges can permanently program glucocorticoid receptors in a tissue-specific manner. These effects involve epigenetic mechanisms.

    Depressing. A lot of the articles found in this journal are also linked to the Phsychosomatic medicine journal. http://www.psychosomaticmedicine.org/content/74/7/717.abstract
    The HPA axis involvement is the very hinge of their phsychosomatic theory. On their pages you will find it linked to fibromyalgia, asthma, depression, pain and fatigue states.
    I have no problem seeing this theory as plausible, i just ..HOPE ITS NOT TRUE!
    Because, what can you do with a permanently altered HPA function from past stress??
    Sueing my parents isnt going to cut it.
    August59 likes this.
  17. nanonug

    nanonug Senior Member

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    Sing likes this.
  18. nanonug

    nanonug Senior Member

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    This is a very astute observation and one with which I agree. Physics has "theoretical physicists" trying to make sense of experiments. I don't think medicine has the same well organized gang of people. On top of that, most people that pursue the medical field aren't that good at Mathematics which hinders their ability to create and test models.
  19. nanonug

    nanonug Senior Member

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  20. beaverfury

    beaverfury beaverfury

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    Cheers, nanonug!

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