HPA Axis & Cortisol Treatment

Discussion in 'Fibromyalgia Main Forum' started by mezombie, Jan 24, 2009.

  1. mezombie

    mezombie Member

    Well, this is new and different!

    The authors of this study suggest that lowering cortisol for a short period of time may be a better treatment for some forms of "CFS" than cortisone (Cortef or Hydrocortisone) supplementation. The focus of the treatment is to optimize the function of the Hypothalamic-Pituitary-Adrenal(HPA) axis. Previous studies have shown that fatigue often results when the HPA axis isn't working as it should.

    Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction.

    Journal: PLoS Comput Biol. 2009 Jan;5(1):e1000273. Epub 2009 Jan 23.

    Authors: Ben-Zvi A, Vernon SD, Broderick G.

    [1] Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, Canada,
    [2] The CFIDS Association of America, Charlotte, North Carolina, United States of America,
    [3] Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    NLM Citation: PMID: 19165314

    The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered
    in the development of treatment strategies.

    Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be
    further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels.

    Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed
    that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions.

    Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning.

    [Note: This is an Open Access article, the full text of which is available fo free at
    http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1000273 ]

    [This Message was Edited on 01/24/2009]
  2. mezombie

    mezombie Member

    I checked out the full article, and it does appear that the researchers used a mathematical model.

    They determined that ACTH was a better marker for optimal hypothalamic-pituitary-adrenal (HPA) axis function than cortisol.

    If cortisol is dangerously low to begin with, the authors concede that this situation would have to be dealt with first.

    I didn't make it through the entire article. Maybe you can and report back to us!

    This study isn't using any of the CDC's "CFS" definitions. It's using a model of HPA axis function, which is disrupted in a lot of diseases.

    I changed the title of my first post to focus on HPA axis function. It seems to me that the article is implying that increasing overall HPA axis function is better served by a short period of decreasing cortisol rather than increasing it.

    Most cortisol replacement treatment is based on tests which only look at the adrenal component of the HPA axis by testing cortisol levels and/or looking for "adrenal fatigue".

    [This Message was Edited on 01/24/2009]
  3. SnooZQ

    SnooZQ New Member

    The main idea here assumes a perfectly responsive pituitary & HPA axis. If we all had that, would we even have CFS to begin with?

    I suspect this computer model is based on what is known about typical HPA axis function. The little bit of research I've seen suggests that quite a few w/CFS have somewhat atypical, very sensitive HPA functioning.

    The comments about cytokines were very insightful & IMO worth serious consideration before implementing the computer model into a practical experimental design.

    I'm all for challenging regulatory processes with negative feedback loops, as long as I'm not the first ... or even in the first hundred to try it.

    Low dose naltrexone (LDN) therapy is based on a similar line of reasoning and use of negative feedback loop. I've benefitted significantly from that therapy, but not everyone has a great result. It's a crapshoot out there, folks!

    Best wishes.
  4. spacee

    spacee Member

    I heard on 60 minutes tonight that of 10 things studied on mice, only one comes out as actually benefiting humans.



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