Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

[ScottTriGuy]

https://www.frontiersin.org/article...=EMLX&utm_campaign=PRD_FEOPS_20170000_ARTICLE

Here the hypothesis is advanced that maladaptive mechanisms that prevent recovery in some intensive care unit (ICU) patients may also underlie Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these mechanisms are: (a) suppression of the pituitary gland's pulsatile secretion of tropic hormones, and (b) a “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. This hypothesis should be investigated through collaborative research projects.

 

[bensmith]

Wow interesting. I know its just a theory but cool. Would also be sweet as we would have more hope of development.

 

[Notgivingupyet]

@thingsvarious I read this and thought of your thread(s)

 

[Wishful]

Darn, the paper doesn't include any "if this hypothesis is true, then <this treatment> should work". It doesn't even include any "if this hypothesis is correct, then <certain abnormalities> should show up in tests". It does point out the need for measuring variations in factors over a time period.

 

[Alvin2]

I don't buy this for a second. It sounds like the author is straining to do some explaining.
But if they want to try pumping people full of hormones and some antioxidants they can argue how messy data proves their hypothesis and when given to people with ME/CFS fails they can argue that there is some other Rube Goldbergian explanation at play.

 

[sue1234]

I saw this posted elsewhere, so sorry if it has been posted and I didn't see it.

https://www.frontiersin.org/article...sh1DtqhgsgjLEaPEnwLcmBKhxqyv2PtsMyQfWRSZj7EmE

I couldn't read it all just now, as my brain doesn't want overload today, but it keeps referring back to apparently the pituitary not putting out it's hormones, specifically ACTH to spur on cortisol production. That sounds like secondary adrenal insufficiency to me, which I recently am showing labs to reflect this.

 

[Gingergrrl]

Thank you for posting this and I received an e-mail from OMF today re: this same paper titled, "OMF funded research paper published". The e-mail was from Jonas Bergquist, MD, PhD at Uppsala University and it said:

On behalf of my team at the ME/CFS Collaborative Research Centre at Uppsala University, I am pleased to share our paper entitled, “Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome” was recently published in Frontiers in Medicine!

Thanks in part to funding from Open Medicine Foundation (OMF), my team’s publication describes the overlaps between prolonged critical illness and ME/CFS. The hypothesis is that mechanisms that prevent recovery in some intensive care unit patients may also underlie people with ME/CFS. We are hopeful that this article will allow researchers in both communities to understand the similarities between the conditions and thereby further collaborations that could help improve the lives of patients across these diseases.

Here is the first paragraph of the research paper (and the bolding is mine):

Here the hypothesis is advanced that maladaptive mechanisms that prevent recovery in some intensive care unit (ICU) patients may also underlie Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these mechanisms are: (a) suppression of the pituitary gland's pulsatile secretion of tropic hormones, and (b) a “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. This hypothesis should be investigated through collaborative research projects.

I tried to read the paper but sadly didn't quite understand it. BUT... I am hoping that someone here can explain it to me because I have the exact issue mentioned in the paper (secondary adrenal insufficiency due to pituitary suppression) and therefore not being able to create enough ACTH to stimulate my adrenals to create enough Cortisol. Because of this issue, I have no choice but to remain on Cortef (hydrocortisone) indefinitely. I also have low thyroid functioning. I bolded both of those issues above in the first paragraph of the article.

I don't quite understand the connection to ICU patients or ME/CFS (vs. my issue being an endocrine problem). Without the Cortef and thyroid med, I definitely 100% have fatigue, low stamina, and many other symptoms that affect my ability just to function and stay awake. And if I stopped the Cortef (hydrocortisone), I would be at risk of an adrenal crisis which could even be fatal. But I am still unclear how this relates to ICU patients and ME/CFS and am hoping someone can explain it to me. Thank you in advance for any feedback.

 

[leokitten]

@Wishful they do specifically show what experiment can initially be used to test this hypothesis. It’s the same experiment they did in the early 1990s that resulted in a major leap in understanding for the pathophysiology of chronic critical illness, which was basically a mystery before that.

This biphasic pattern of the endocrine system during critical illness, however, is not readily observable in single or average measurements of circulating tropic and non-tropic hormone concentrations—which are a function of both hormone release and elimination from the blood stream. This pattern was thus only discovered in the early 1990s with measurements of the frequency and amplitude of pituitary secretions (i.e., pulsatility) performed as often as every 10 min over 24 h on ICU patients.

In sum, the HPA axis dysfunctions in ME/CFS are not unlike the dysfunctions in prolonged critical illness. However, to our knowledge a comprehensive study of the pituitary pulsatile secretions of ACTH in ME/CFS patients—which proved revelatory in understanding prolonged critical illness—does not yet exist. The relationship between the pituitary's pulsatile ACTH secretions, severity of illness, the integrity and function of adrenal glands and resulting physiological alterations in ME/CFS thus remains largely unexplored.

This study should be done for an ME cohort against normal controls and OMF should fund the study if they are truly interested in seeing the hypothesis through, at least to disprove it so we can finally shut the door on the endocrine pathology hypothesis of ME.

@Alvin2 the paper does generally refer to the chronic critical illness literature on treatment paradigms. I reviewed some of the literature and no they know that treatment with exogenous hormones doesn’t work and can make the illness worse.

Multiple researchers in this field believe that careful treatment with hypothalamic releasing hormones/factors will restore the anterior pituitary gland back to a normal state and bring about recovery from CCI. They have been urging for trials of this treatment since what looks like the early 2000s, but looks like still to date no trial has been done which is shame.

 

[Alvin2]

@Alvin2 the paper does generally refer to the chronic critical illness literature on treatment paradigms. I reviewed some of the literature and no they know that treatment with exogenous hormones doesn’t work and can make the illness worse.

I'm no scientist but i do think they are grasping at straws.
It would take a lot to convince me otherwise but i suspect they are at best describing something far downstream of the disease mechanism if they are correct about this at all.

 

[leokitten]

I'm no scientist but i do think they are grasping at straws.
It would take a lot to convince me otherwise but i suspect they are at best describing something far downstream of the disease mechanism if they are correct about this at all.

This hypothesis actually has evidence showing that this central endocrine dysfunction has substantial damaging systemic effects such immune dysfunction, metabolism dysfunction, viral reactivations, and chronic inflammation which is what is seen in chronic critical illness patients.

The paper describes severe ME being the closest in presentation to chronic critical illness and ME illness severity would be correlated with severity of hypothalamic and pituitary dysfunction.

 

[Alvin2]

This hypothesis actually has evidence showing that this central endocrine dysfunction has substantial damaging systemic effects such immune dysfunction, metabolism dysfunction, viral reactivations, and chronic inflammation which is what is seen in chronic critical illness patients.

The paper describes severe ME being the closest in presentation to chronic critical illness and ME illness severity would be correlated with severity of hypothalamic and pituitary dysfunction.

Maybe they are onto something and more evidence will be forthcoming?
Until then i am highly skeptical .

 

[Rufous McKinney]

showing that this central endocrine dysfunction has substantial damaging systemic effects such immune dysfunction, metabolism dysfunction, viral reactivations, and chronic inflammation which is what is seen in chronic critical illness patients.

is this related to the sepsis process?

 

[Levant]

It's interesting that the typically recommended recovery path for HPA axis dysfunction is: rest, relaxation, sleep, and limiting inflammation. Mirrors the approach to me/cfs I'd say.
I don't see them tie PEM into their hypothesis though, unless I missed that. Curious how that would fit into their theory.

 

[Rufous McKinney]

Multiple researchers in this field believe that careful treatment with hypothalamic releasing hormones/factors will restore the anterior pituitary gland back to a normal state and bring about recovery from CCI.

Is this somehow tied to the collagen breakdown? Connecting hormones to actual cranial instability?

 

[Rufous McKinney]

I'm just puzzling how...other hypotheses might interface with these hypotheses.

Something in the blood/plasma...

Something which leaks from the gut and creates all that, a factor in PEM in my case (if my gut worsens, I tend to crash on bad gut days).

The metabolic trap theory.

The mechanical theory.

 

[Alvin2]

I'm just puzzling how...other hypotheses might interface with these hypotheses.

Something in the blood/plasma...

Something which leaks from the gut and creates all that, a factor in PEM in my case (if my gut worsens, I tend to crash on bad gut days).

The metabolic trap theory.

The mechanical theory.

I am reminded of this Simpsons clip

 

[Levant]

I'm just puzzling how...other hypotheses might interface with these hypotheses.

Something in the blood/plasma...

Something which leaks from the gut and creates all that, a factor in PEM in my case (if my gut worsens, I tend to crash on bad gut days).

The metabolic trap theory.

The mechanical theory.

True, this endocrine system dysregulation theory could be part of a larger puzzle.

In that case you'd be looking for something more upstream, e.g. the vagus nerve

 

[Gingergrrl]

I am reminded of this Simpsons clip

That was very funny

I wrote a post re: this research paper in another thread (b/c I didn't see this one ) and then the two threads got merged together. My post is now #7 in this current thread and I was wondering if you had any thoughts about it @Alvin2 (since you & I have discussed ACTH & Cortisol so many times).

I'm trying to understand whether my current situation w/pituitary suppression of ACTH, plus my thyroid issues, is connected to this research (or if it is totally unrelated)? ME/CFS turned out not to be my diagnosis but I have multiple other autoimmune problems. I'm trying to figure out how the issues in this research paper relate to ICU patients and to ME/CFS patients (in the title of this study).

 

[leokitten]

is this related to the sepsis process?

I don’t believe so this is during the chronic critical illness stage after they’ve survived the acute phase. People are eventually discharged from hospital and have to suffer through this at home.

 

[leokitten]

I'm just puzzling how...other hypotheses might interface with these hypotheses.

Something in the blood/plasma...

Well probably some or all of the various ME pathophysiology hypotheses are going to be wrong, so not sure if it makes sense to try and make things fit together.

From the paper, connecting the hypothesis to the ME metabolic dysfunction studies. Maybe it’s not a single “something in the blood” but multiple aberrant levels of hormones, cytokines, and oxidative stress markers in the blood.

Energy metabolic defect: Researchers have found impairment in energy production (205, 206), reduced mitochondrial activity (207–209) and irregularities in the metabolites of ME/CFS patients (210, 211) —suggesting that they experience a hypometabolic or “dauer” state (212). Our hypothesis is compatible with analyses that emphasize metabolic defects in ME/CFS. Indeed, the suppression of pituitary secretions, depressed thyroid hormone function, O&NS and immune system dysfunction—hallmarks of prolonged critical illness—have severe impacts on metabolism, including on glucose utilization and mitochondrial activity (see section A “Vicious Circle” Perpetuating Illness). Certainly, prolonged critical illness resembles a hypometabolic “dauer” state as well.