by Helen Borel,RN,MFA,PhD
Just as I'd completed the last chapter - "Basic Ingredients for Enhanced Daily Living" - of my Living With and Recovering From CHRONIC FATIGUE SYNDROME: Debilitating Immunopathic Relapsing Encephalomyelitis (1992), yet another scientific
study surfaced that I felt compelled to present and discuss in this book. Thus, it became
the book's two-page Addendum:
A Key Recent Research Report and Commentary
The CRH-Cortisol Connection
"Hormonal deficiencies in the endocrine systems and brains of people with CFS:DIRE,
which may explain many of the disorder's symptoms, have recently been identified
(Demitrack, M.A., et al. Journal of Clinical Endocrinology and Metabolism, Dec. 1991).
The researchers found blood and urine levels of the adrenal hormone cortisol to be lower in 30 CFS:DIRE patients than in 72 healthy subjects. Lethargy and fatigue are known symptoms of even the subtlest cortisol deficiency."
"Normally, the adrenals secrete cortisol in response to stress. When the body reacts to a stressor - poisons, allergens, viruses, bacteria, or emotional crisis, or even intense creative and intellectual effort, for example - a complex endocrine process ensues. First, the hypothalamus secretes corticotropin-releasing hormone (CRH) which induces the pituitary to secrete ACTH. The ACTH then stimulates adrenal production of cortisol."
Cortisol Deficiency in ME/CFS:DIRE
"The cortisol deficiency noted in CFS:DIRE patients has been attributed by Demitrack et al. to CRH deficiency. This is considered an important finding because, beside its effects on ACTH and cortisol secretion, energy levels are normally increased by the direct action of CRH on the brain. This could mean that a CRH deficiency might contribute to some of the exhaustion prevalent in CFS:DIRE. But both the CRH and cortisol deficiencies together can affect symptomatology and the course of the illness, the investigators claim."
"This type of biochemical imbalance is also seen in patients with depressive disorders due to unbalanced biochemistry such as certain endogenous depressions, hypothyroidism and Cushing's Syndrome. Dr. Philip W. Gold, one of the study's authors, asserted that 'Finding a common central nervous system [CNS] defect in these illnesses underscores the fact that they are all fundamentally medical disorders.' He includes CFS:DIRE in this 'medical disorder' category."
Blaming the Brain as Etiologic
When the Brain is Targeted by a Derailed Immune System
"As a result of this small study, there is therefore a hypothesis that in CFS:DIRE there is
insufficient stimulation of certain parts of the brain by cortisol or CRH, accounting for
symptoms. However, the scientists pursuing these defects as cause rather than as but one of many untoward effects of other pathologic processes, such as primary immune dysfunction (idiopathic or toxic in etiology), hypersecretions of cytokines, viral reactivations, and recurrent brain fevers - encephalitis or encephalomyelitis - are barking up the wrong tree."
"Because, if you flood the brain with endogenous toxins, reawakened viral hordes, and chronic recurrent heat from fevers undetectable by rectal or oral thermometers, you can pretty well cripple neurologic, neurohormonal and neuroimmune functions, both at the cellular structural level and at the biochemical pathways level. Neuroimmunal biochemical communications will go haywire. This in turn will have a profound effect on hypothalamic and adrenal function! The CRH-cortisol problem, therefore, I believe, is but one pathologic result of profound immune dysregulation which contributes to the multisystem disorders characteristic of CFS:DIRE."
"Dr. Stephen E. Straus, another contributor to this CRH-cortisol investigation, points out, 'Because cortisol is a potent suppressor of immune responses, a mild reduction in cortisol levels could allow the immune system to remain overactive, leading to findings such as higher-than-normal antibody levels.' Immune overreactivity and high antibody levels are characteristic of CFS:DIRE."
In summation, at the close of my 1992 book, I concluded: "Hypothetically, then, treatment with cortisol could correct the CRH-cortisol problem which might reduce CFS:DIRE symptoms. However, exogenous administration of cortisol would cause hypothalamic secretion of CRH to shut down - due to adequate external cortisol supply -
producing a dangerous exacerbation of CRH deficiency. Also, such a treatment presupposes that the CRH-cortisol axis deficiencies are primary and would ignore the real underlying pathology - primary immune dysregulation (due to some as yet unpinpointed cause, probably poisoning [here I'm referring to toxins in air, water, food, household chemicals, etc.]). The value of investigating the CRH-cortisol connection in CFS:DIRE is it's a new avenue of possible discovery of the mechanisms producing the characteristic relapsing brain fevers, exhaustions and muscular pain."
[The above is quoted in toto from the 2-page addendum in my 1992 book which
provided the scientific facts and the conclusions I arrived at 25 years ago!]
~~~~~~~~~~~~~
You'll note, in the following abstract of their 2017 paper in Molecular Neurobiology, that these 21st Century scientists arrive at the exact same conclusions I concluded in 1992. Here is the abstract of the results of that directly related report which reviewed 167 studies published between 1989 and 2015, several of which I referenced in my book
so long ago.
"Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/ Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosated Pathways" (Molecular Neurobiology, November 2017, Vol. 54, Issue 9, pp. 6806-6819)
There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity.
Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS.
Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS.
Mechanistic explanations comprise increased levels of tumor necrosis factor-Alpha,
T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-Beta, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms.
HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.
Morris, G., Anderson, G. & Maes, M. Mol Neurobiol (2017) 54:6805.
To access this entire paper, you'll have to subscribe to this Springer publication at this site: https://doi.org/10.1007/s12035-016-0170-2
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As I've pointed out in other of my ME RESEARCH CENTRAL blogs, all the identical
information about this pandemic disease rapidly accumulating these days, was known more than a quarter century ago. I reported it from the scientific literature then (1992).
And I came to the same conclusions in 1992 that these scientists arrived at in 2017.
I only emphasize this because IT'S TIME FOR SYMPTOMATIC TREATMENTS
while we await definitive science that pins down exact etiology(ies).
(c) Copyright 1992 to 2018 by Dr. Helen Borel. All rights reserved.
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