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

[Alvin2]

That was very funny

Glad you enjoyed it
This is the longer version:

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 don't know where to start. Its possible they are describing something downstream if its not an artifact.
But an immune component seems to be involved somehow though we cannot pin down how. This may be related and maybe my immune system knowledge is insufficient but this does not jive all that well imo.
I remember Dr Klimas and a few others speculating that ME may be caused by several systems operating out of spec and this seems to be a variation on that theme.
But if it were this simple we can fix it, and many people have tried various treatments along these lines and subtle abnormalities being the mechanism of such a major disease is not very likely.

And this rests on a shaky foundation, not only do other diseases have much simpler mechanisms, this seems contrived to explain something that can't be explained otherwise due to lack of understanding. A disease typically has a core upstream cause/mechanism that is Occam's razor level simple.

That said i could be wrong on all fronts, though i'm not betting on it.
I think this is worth looking into further but i'm not yet convinced it has anything to do with anything beyond downstream ME/CFS.

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).

That one is well above my pay grade so I cannot give an informed opinion. Though ME/CFS as a wastebasket diagnosis is a royal headache because its too easy to lump in the wrong thing, call it ME/CFS and all roads lead to Rome even when they involve flying to the moon and back.

I'm not sure if i am making any sense since its almost bed time for me, but i will revisit tomorrow when not fighting fatigue.

 

[leokitten]

There’s also more details on the effect of this hypothesis on metabolic dysfunction in the entire “A “Vicious Circle” Perpetuating Illness” section of the paper.

I recommend it’s worth reading the entire paper before coming to conclusions. The paper describes that this hypothesis wouldn’t be a downstream effect of some other root pathophysiology, because in chronic critical illness they have shown that indeed the root problem is central hypothalamus and pituitary gland dysfunction and this causes a vicious self-perpetuating cycle across the endocrine system. It has a massive systemic effect across multiple systems that is seen in chronic critical illness.

 

[Rufous McKinney]

but multiple aberrant levels of hormones, cytokines, and oxidative stress markers in the blood.

yes thats certainly also likely.

my brain decided dauer and sepsis must be friends.

 

[leokitten]

I would also encourage people to read up on the functions of the hypothalamus and pituitary gland. This system is central to maintaining homeostasis and directly performs or regulates so many vital bodily functions. To me it’s no surprise that any dysfunction arising from this system would have disastrous effects throughout the body.

Everything the hypothalamus and pituitary gland perform or regulate are to me directly linked to ME symptoms, and here is just a subset: fatigue, sleep, circadian rhythms, body temperature, emotions, appetite and thirst, energy maintenance, stress control, blood pressure and heart rate, disgestion, perspiration, and more.

 

[unicorn7]

This reminds me a lot of the topic of @thingsvarious

I had an extreme yes-feeling with this paper Really hope they will take this further and find the funding to (finally) do a real in-depth study on this topic.

 

[Rufous McKinney]

Everything the hypothalamus and pituitary gland direct perform or regulate are to me directly linked to ME symptoms, and here is just a subset: fatigue, sleep, circadian rhythms, body temperature, emotions, appetite and thirst, energy maintenance, stress control, blood pressure and heart rate, disgestion, perspiration, and more.

I completely agree this is a very messed up bit of our anatomy. And mostly, every thing you've listed there is not working correctly, here.

In my case, I experience a whole lot of tissue swelling on a rather regular 24 hour cycle. Some type of angiodema.

So personally, all this swollen tissue is right next door to the pit/hyptho. I"ve been convinced for some time now that this is a key messed up area.

So how can the proper instructions be sent out when the tissue is swollen, compressing adjacent tissues, etc. My teeth are being squeezed out of the pulp? That type of fun stuff.

 

[Donsboig]

There's some very interesting research from Dr Higgins in Cambridge linking intracranial hypertension and ME/CFS symptoms. When the hypertension is resolved the symptoms often improve significantly, or even disappear.

The evidence is not settled, but his research seems promising.

The paper discussed in this thread made me think of intracranial hypertension because one of the effects can be a squashed or flattened pituitary gland ("empty sella" on MRI). To my knowledge, Dr Higgins isn't explicitly linking squashed pituitary to ME, that's my own thought

Example paper - What do lumbar puncture and jugular venoplasty say about a connection between chronic fatigue syndrome and idiopathic intracranial hypertension?

Abstract:

INTRODUCTION: Similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) invite speculation that they may be related. Cranial venous outflow obstruction plays a role in the development of IIH. Could it be a factor in chronic fatigue? This paper attempts to evaluate an investigative approach to chronic fatigue syndrome that allows for this possibility.

METHODS: Since 2007, patients attending a specialist clinic at our institution diagnosed with chronic fatigue syndrome and with prominent headache have been offered CT venography, lumbar puncture and a trial of cerebrospinal fluid withdrawal looking for IIH. Also, if CT venography revealed focal narrowing of the jugular veins, patients were offered catheter cerebral venography and jugular venoplasty attempting to establish their clinical significance.

RESULTS: In the 29 patients investigated to date, the mean cerebrospinal fluid (CSF) pressure was 19 cm H2O (range 12 – 41 cm H2O). Twenty-five patients responded positively to CSF withdrawal and in 5 the CSF pressures were high enough to allow an unequivocal diagnosis of IIH while in the remaining 20, symptoms improved with lumbar puncture even though CSF pressures were within the normal range. Twenty-one patients had focal narrowing of one or both internal jugular veins on CT venography. Fourteen of these have had jugular venoplasty, all of whom reported an improvement in symptoms afterwards lasting from a few minutes to more than 1 month.

CONCLUSIONS: Chronic fatigue syndrome may represent an incomplete form of IIH. Cranial venous outflow obstruction deserves further investigation as a possible aetiological factor.

 

[Alvin2]

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).

I gave this some more thought and we don't fully understand how pituitary control of hormones works (but we know a fair bit but not the whole story). That said this paper strikes me as metaphorically tinkering with adverbs. In many cases we can supplement hormones and if that was enough to fix the symptoms of ME it would be standard medical procedure by now.
Quite a few people with ME seem to have hormone imbalances but treating them only fixes the imbalance and is not getting them to normal person functioning.

 

[unicorn7]

In many cases we can supplement hormones and if that was enough to fix the symptoms of ME it would be standard medical procedure by now.
Quite a few people with ME seem to have hormone imbalances but treating them only fixes the imbalance and is not getting them to normal person functioning.

I wish I had your trust in standard medical procedures I know that the treatment for panhypopitarism is far from optimal and the treatment of hypothyroidism is pretty bad actually. (see: stop the thyroidmadness website). Lots op people getting stuck with horrible symptoms.

So we know lots of people have hormones imbalances, but when we treat (just one of them) these people are not functioning as a healthy person? Is that not a bit too much too ask? Getting back to normal people functioning would be a cure, I agree that this is maybe not a cure.

Even if It's probably not the primary problem or it's not a total cure, does that mean it wouldn't be a good thing to treat and give people some quality of life? These solutions are so simple and cheap, even if people get 10, 20 or 30% of their life back with some thyroid or cortisol, would that not be a lot better than nothing?

 

[Alvin2]

I wish I had your trust in standard medical procedures I know that the treatment for panhypopitarism is far from optimal and the treatment of hypothyroidism is pretty bad actually. (see: stop the thyroidmadness website). Lots op people getting stuck with horrible symptoms.

Actually i don't, i could write a novel explaining my position (if i had that kind of cognitive functioning).

So we know lots of people have hormones imbalances, but when we treat (just one of them) these people are not functioning as a healthy person? Is that not a bit too much too ask? Getting back to normal people functioning would be a cure, I agree that this is maybe not a cure.

If a series of hormones are deficient then one can treat all the deficiencies. Its not like we are limited to only treating one deficiency per human.

Even if It's probably not the primary problem or it's not a total cure, does that mean it wouldn't be a good thing to treat and give people some quality of life? These solutions are so simple and cheap, even if people get 10, 20 or 30% of their life back with some thyroid or cortisol, would that not be a lot better than nothing?

All deficiencies should be treated and the benefit is a good thing. My point is that if ME were simply a series of hormonal deficiencies then treating them would be a treatment for ME. Not a cure because patients would probably have to take those hormones for life but so what if it gets us to normal person functioning.
But thats not the case here.

 

[bensmith]

There's some very interesting research from Dr Higgins in Cambridge linking intracranial hypertension and ME/CFS symptoms. When the hypertension is resolved the symptoms often improve significantly, or even disappear.

The evidence is not settled, but his research seems promising.

The paper discussed in this thread made me think of intracranial hypertension because one of the effects can be a squashed or flattened pituitary gland ("empty sella" on MRI). To my knowledge, Dr Higgins isn't explicitly linking squashed pituitary to ME, that's my own thought

Example paper - What do lumbar puncture and jugular venoplasty say about a connection between chronic fatigue syndrome and idiopathic intracranial hypertension?

Abstract:

INTRODUCTION: Similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) invite speculation that they may be related. Cranial venous outflow obstruction plays a role in the development of IIH. Could it be a factor in chronic fatigue? This paper attempts to evaluate an investigative approach to chronic fatigue syndrome that allows for this possibility.

METHODS: Since 2007, patients attending a specialist clinic at our institution diagnosed with chronic fatigue syndrome and with prominent headache have been offered CT venography, lumbar puncture and a trial of cerebrospinal fluid withdrawal looking for IIH. Also, if CT venography revealed focal narrowing of the jugular veins, patients were offered catheter cerebral venography and jugular venoplasty attempting to establish their clinical significance.

RESULTS: In the 29 patients investigated to date, the mean cerebrospinal fluid (CSF) pressure was 19 cm H2O (range 12 – 41 cm H2O). Twenty-five patients responded positively to CSF withdrawal and in 5 the CSF pressures were high enough to allow an unequivocal diagnosis of IIH while in the remaining 20, symptoms improved with lumbar puncture even though CSF pressures were within the normal range. Twenty-one patients had focal narrowing of one or both internal jugular veins on CT venography. Fourteen of these have had jugular venoplasty, all of whom reported an improvement in symptoms afterwards lasting from a few minutes to more than 1 month.

CONCLUSIONS: Chronic fatigue syndrome may represent an incomplete form of IIH. Cranial venous outflow obstruction deserves further investigation as a possible aetiological factor.

should we then be seeing a lot of eye pressure within cfs community? Has anybody had theirs checked? Surely that would be a noticed variable by now.

 

[thingsvarious]

I highly doubt that CFS/ME is a "single entity" for which one single cause and/or treatment works for everyone. It is a highly heterogeneous conditions although I believe that for many hormonal imbalances play a major role. And no, these issues can often not seen on blood tests

 

[Donsboig]

should we then be seeing a lot of eye pressure within cfs community? Has anybody had theirs checked? Surely that would be a noticed variable by now.

I have slight enlargement of the optic nerve sheath visible on MRI, but no signs of papilloedema. Sometimes I have a very mild feeling of pressure behind the eyes.

I think these symptoms can indicate intracranial hypertension, but you can have IH without them.

Of course, I still don't know for sure if I have IH, or if my squashed jugulars are causing my CFS symptoms. But I will report back when I do. There are certainly some other people in a similar situation to me who respond well to CSF withdrawal from a lumbar puncture, albeit temporarily, this is what Dr Higgins' research shows

(I should be clear that I'm absolutely not saying I think this is the root cause of all ME/CFS, just that the connection struck me as interesting!)

 

[Gingergrrl]

But if it were this simple we can fix it, and many people have tried various treatments along these lines and subtle abnormalities being the mechanism of such a major disease is not very likely.

I agree and my own personal opinion is that the endocrine problems discussed in this paper are not the cause of ME/CFS but that there is a link between the two (and that many people with ME/CFS have co-morbid endocrine problems and/or feel some percentage of improvement when their endocrine problems are addressed).

Though ME/CFS as a wastebasket diagnosis is a royal headache because its too easy to lump in the wrong thing, call it ME/CFS and all roads lead to Rome even when they involve flying to the moon and back.

I agree that this is a major problem both for those who ultimately do have an ME/CFS diagnosis and for those who do not. It means that neither group of people are properly diagnosed or treated and it completely muddies the research when you have subjects with "CFS" diagnoses who actually have a different diagnosis.

because in chronic critical illness they have shown that indeed the root problem is central hypothalamus and pituitary gland dysfunction and this causes a vicious self-perpetuating cycle across the endocrine system. It has a massive systemic effect across multiple systems that is seen in chronic critical illness.

Thank you for clarifying that and I did not realize that the hypothalamus & pituitary play such a major role across so many different illnesses!

I would also encourage people to read up on the functions of the hypothalamus and pituitary gland. This system is central to maintaining homeostasis and directly performs or regulates so many vital bodily functions. To me it’s no surprise that any dysfunction arising from this system would have disastrous effects throughout the body.

I am hoping you can explain something that I am still confused about. Can someone have "pituitary suppression" of hormones like ACTH without also having a problem with their hypothalamus? Or if someone had inflammation & suppression of their pituitary would it automatically mean that they also had a problem with their hypothalamus? I don't want to take this off-track and I was diagnosed last year w/pituitary suppression (based on blood tests for ACTH & Cortisol combined w/my symptoms when I attempted to taper off Cortef). But I was not able to do an MRI of my brain b/c I am deathly allergic to contrast dyes.

Also, do you know if "pituitary inflammation" would be the opposite of "Empty Sella Syndrome" which I read about in many threads? Or are they not opposites?

Quite a few people with ME seem to have hormone imbalances but treating them only fixes the imbalance and is not getting them to normal person functioning.

I agree with you that treating hormone imbalances does NOT cure ME/CFS. And in my case, it didn't "fix" the hormone imbalances vs. it provides symptom management and brings my adrenal and thyroid hormones into a normal range on blood tests. But as far as I know, I will take Cortef & thyroid med for the rest of my life. I did a VERY slow taper off Cortef (almost 2.5 years) but my brain was never able to kick in and produce the ACTH on it's own and it became dangerous and I have to wear a medic alert bracelet that I am on Cortef. I had really hoped to find a way to come off of it but so far it is not possible.

Not a cure because patients would probably have to take those hormones for life but so what if it gets us to normal person functioning.

I agree with this statement but the annoying part is that some of these hormones have side effects (both short-term and long-term) and they are not completely benign.

 

[Alvin2]

I agree and my own personal opinion is that the endocrine problems discussed in this paper are not the cause of ME/CFS but that there is a link between the two (and that many people with ME/CFS have co-morbid endocrine problems and/or feel some percentage of improvement when their endocrine problems are addressed).

It could be something downstream.

I agree that this is a major problem both for those who ultimately do have an ME/CFS diagnosis and for those who do not. It means that neither group of people are properly diagnosed or treated and it completely muddies the research when you have subjects with "CFS" diagnoses who actually have a different diagnosis.

Yeah. We need a validated diagnostic test for ME/CFS.

I agree with you that treating hormone imbalances does NOT cure ME/CFS. And in my case, it didn't "fix" the hormone imbalances vs. it provides symptom management and brings my adrenal and thyroid hormones into a normal range on blood tests. But as far as I know, I will take Cortef & thyroid med for the rest of my life. I did a VERY slow taper off Cortef (almost 2.5 years) but my brain was never able to kick in and produce the ACTH on it's own and it became dangerous and I have to wear a medic alert bracelet that I am on Cortef. I had really hoped to find a way to come off of it but so far it is not possible.

I agree with this statement but the annoying part is that some of these hormones have side effects (both short-term and long-term) and they are not completely benign.

That sucks. Side effects from taking hormones is something to consider, it would be nice if we could develop a better solution.

 

[HRManager]

Very interesting reading

"We here provide an overview of treatment trials for prolonged intensive care unit (ICU) patients and theorize about their relevance for potential treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these treatment trials generally target: (a) the correction of suppressed endocrine axes, notably through a “reactivation” of the pituitary gland's pulsatile secretion of tropic hormones, or (b) the interruption of the “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. There are significant parallels in the treatment trials for prolonged critical illness and ME/CFS; this is consistent with the hypothesis of an overlap in the mechanisms that prevent recovery in both conditions. Early successes in the simultaneous reactivation of pulsatile pituitary secretions in ICU patients—and the resulting positive metabolic effects—could indicate an avenue for treating ME/CFS. The therapeutic effects of thyroid hormones—including in mitigating O&NS and inflammation and in stimulating the adreno-cortical axis—also merit further studies. Collaborative research projects should further investigate the lessons from treatment trials for prolonged critical illness for solving ME/CFS."

https://www.frontiersin.org/articles/10.3389/fmed.2021.672370/full

 

[bensmith]

Cool, ty

 

[Martin aka paused||M.E.]

Existing thread https://forums.phoenixrising.me/thr...elitis-chronic-fatigue-syndrome-me-cfs.82761/