Is ME/CFS caused by biological stress and perpetuated by high catecholamines and low blood volume?

[Leopardtail]

The stuff to do with mood hormones is largely from Psychiatry and hence a bit science-light. They measure hormone levels, assess mood then work out what correlations occur. The field of Neuro-endocrinolgy (hard science about mood hormones) is fairly new and still has some way to go.

The hormones are often weird in that too much or too little often cause versions of the same symptom but via different methods. This makes them a major pain for doctors, they have to extract every symptom form the patient and be very expert to diagnose.

My common sense view:
Serotonin is uplifting - too little produces low mood (the depression most people think of) too much produces agitation (anxious depression).

BTW the Serotonin produced in the gut is independent of that in the brain - it's why you can't eat a Serotonin tablet for depression. It does loads of stuff though, involved in the bowels, regulates the immune system, I suspect we are barely started learning about it.

 

[leokitten]

For some reason the ME/CFS scientific literature on this topic always uses the phrase "high catecholamines" to describe the phenomenon and this is the reason I used it in my title and text, but to be more accurate/specific norepinephrine (NE) is the primary culprit here, not epinephrine (E) aka adrenaline and not dopamine (DA).

Maybe I should have been more specific after seeing post after post with all the confusion and many people thinking that hyperarousal == high adrenaline, it does not. It means high sympathetic nervous system activation and/or dysfunction. I just followed the terminology used in research literature so people can search for it themselves.

Norepinephine (NE) and epinephrine (E) are very different beasts and do very different things in the body. NE is the primary neurotransmitter of the sympathetic nervous system, E is not.

 

[Leopardtail]

@leokitten

The tumour your article referred to raises blood sugar caused massive overproduction of NE. That high blood sugar causes the Aldo under-production and subsequent urination. Were aldo under-production pervasive in ME there would be pervasively elevated levels of Serum Potassium.

Research from the University of Adelaide indicates that is not the case while intra-cellular K is normal to low, extra-cellular K is highly variable., further research indicating benefit from K supplementation raises similar issues.

Research has been performed into both Aldo and AVP showing a very mixed picture. Ditto with NE. The lack of sensory filtering in ME patients (sound, light and pressure sensitivity) especially in more severe patients more strongly supports low NE there is quite a lot research direct evidence indicating this.

Further there is much discussion of hypoglycaemia in ME, again high NE would make that very very unlikely. True hypoglycaemia occurs in substantial numbers of ME patients.

Finally and more personally my NE levels are at the very bottom of normal range. For this particular ME patient this is not correct - yet I pee like a fish.

As I stated earlier the high urination causing havoc seems very likely. The NE part is most certainly not universally correct.

Have you located research evidence indicating a direct connection between NE and lowering of either Aldosterone (without hyperglycaemia) or AVP?

regards,
Leo.

 

[leokitten]

The tumour your article referred to raises blood sugar caused massive overproduction of NE. That high blood sugar causes the Aldo under-production and subsequent urination. Were aldo under-production pervasive in ME there would be pervasively elevated levels of Serum Potassium.

The rise in blood sugar caused by elevated catecholamines is not the primary cause of polyuria and subsequent volume depletion. It just doesn't make your blood sugar go up enough to cause this, not to the levels caused in diabetes mellitus.

It's because elevated levels of NE suppress the renin-angiotensin-aldosterone system (RAAS) which then cause loss of water from your blood.

See the nice schematic on the Wikipedia page under the "Activation" section. http://en.m.wikipedia.org/wiki/Renin–angiotensin_system

Please see other posts in this thread where I mention that this disease very likely changes over time and I believe that in the beginning of the disease process (and likely preceding it) there is a chronic elevated stress response. After some time the body likely just putters out, a lot of damage is done, and later in the disease process you don't see the sympathetic activation anymore.

Also the low aldosterone-high potassium connection doesn't show up at all in laboratory tests, I'm serious. I've had my 24-hr urine aldosterone tested twice and both times it was close to zero and at the same time measured serum potassium which was totally within the normal range. It is of utmost importance for the body to maintain proper levels of electrolytes and it will compensate and do whatever it can in order to do so.

I was fortunate enough to have started lab work within 2 months of getting sick, I didn't do 24-hr catecholamines and metanephrines until a year later but looking back so many basic labs pointed directly to a stress response.

I measured my fasting blood glucose a lot and in the first 9 months or so of this disease it would never go below 95 mg/dL even though before I had low-normal blood glucose, am a thin person and always ate healthy and small portions.

My blood pressure also immediately went into the prehypertension to mild hypertension range the moment I got sick and I couldn't get it to go down no matter what.

In addition my thyroid started going from normal to hyperthyroid over these months, proven by many measurements of TSH and free and total T3 and T4.

There were so many symptoms that pointed to chronic stress response and high sympathetic activation during the beginning of this disease.

Research has been performed into both Aldo and AVP showing a very mixed picture. Ditto with NE. The lack of sensory filtering in ME patients (sound, light and pressure sensitivity) especially in more severe patients more strongly supports low NE there is quite a lot research direct evidence indicating this.

Further there is much discussion of hypoglycaemia in ME, again high NE would make that very very unlikely. True hypoglycaemia occurs in substantial numbers of ME patients.

Finally and more personally my NE levels are at the very bottom of normal range. For this particular ME patient this is not correct - yet I pee like a fish.

As I stated earlier the high urination causing havoc seems very likely. The NE part is most certainly not universally correct.

Again you are talking about symptoms of sufferers later in the disease, well after the process I'm taking about in the beginning has happened and the body has suffered a lot of damage.

Also sorry if there is any confusion here, but I never said in this thread that high catecholamines was directly causing the polyuria and low blood volume. I said it is not certain exactly which causes which, the polyuria and low blood volume could possibly cause the sympathetic activation instead of vice versa.

I have very low aldosterone and almost zero AVP, both measured multiple times to make sure it was true. There is a direct connection between NE and these other blood pressure and volume regulating hormones, but there could have been other ways, like chronic inflammation, contributing to the dysfunction.

 

[Leopardtail]

The rise in blood sugar caused by elevated catecholamines is not the primary cause of polyuria and subsequent volume depletion. It just doesn't make your blood sugar go up enough to cause this, not to the levels caused in diabetes mellitus.

It's because elevated levels of NE suppress the renin-angiotensin-aldosterone system (RAAS) which then cause loss of water from your blood.

See the nice schematic on the Wikipedia page under the "Activation" section. http://en.m.wikipedia.org/wiki/Renin–angiotensin_system

Please see other posts in this thread where I mention that this disease very likely changes over time and I believe that in the beginning of the disease process (and likely preceding it) there is a chronic elevated stress response. After some time the body likely just putters out, a lot of damage is done, and later in the disease process you don't see the sympathetic activation anymore.

Also the low aldosterone-high potassium connection doesn't show up at all in laboratory tests, I'm serious. I've had my 24-hr urine aldosterone tested twice and both times it was close to zero and at the same time measured serum potassium which was totally within the normal range. It is of utmost importance for the body to maintain proper levels of electrolytes and it will compensate and do whatever it can in order to do so.

I was fortunate enough to have started lab work within 2 months of getting sick, I didn't do 24-hr catecholamines and metanephrines until a year later but looking back so many basic labs pointed directly to a stress response.

I measured my fasting blood glucose a lot and in the first 9 months or so of this disease it would never go below 95 mg/dL even though before I had low-normal blood glucose, am a thin person and always ate healthy and small portions.

My blood pressure also immediately went into the prehypertension to mild hypertension range the moment I got sick and I couldn't get it to go down no matter what.

In addition my thyroid started going from normal to hyperthyroid over these months, proven by many measurements of TSH and free and total T3 and T4.

There were so many symptoms that pointed to chronic stress response and high sympathetic activation during the beginning of this disease.



Again you are talking about symptoms of sufferers later in the disease, well after the process I'm taking about in the beginning has happened and the body has suffered a lot of damage.

Also sorry if there is any confusion here, but I never said in this thread that high catecholamines was directly causing the polyuria and low blood volume. I said it is not certain exactly which causes which, the polyuria and low blood volume could possibly cause the sympathetic activation instead of vice versa.

I have very low aldosterone and almost zero AVP, both measured multiple times to make sure it was true. There is a direct connection between NE and these other blood pressure and volume regulating hormones, but there could have been other ways, like chronic inflammation, contributing to the dysfunction.

The higher Catechols at the early stage of the disease (but not later) are pretty common medical opinion so with that clarification I would agree yes, early in the disease high levels would be expected. I saw material in which you discussed a vicious cycle of high Catechols and high urination. That was where things fell down without the clarification you give now - since as the disease progressed and catechols came down that cycle would be broken.

The article on the tumour you cited described very high levels of NE, of high blood sugar occurring as a result - that was the cause of the urination.

I could draw a diagram of the RAD system from memory - but thanks for the link non-the-less.. The Wikpeida article on the Renin-Angiotensin system makes no reference to Norepineprhine stimulating urination and it would be incorrect if it did. It does mention Angiotensin-II raising sympathetic activity. Both major textbooks on Endocrinology (oxford and williams) indicate the exact opposite. NE raises vascular tone (thus pushing up blood pressure) and lowers urination (same goal). If you don't have access to the textbooks (they are hellishly expensive) try checking PubMed there are vast numbers of articles indicating what I am telling you.

There are also FDA guidelines indicating that NE may be used for hypotension urination would acheive the exact opposite. Again that is something you can look up without cost.

Vis-a-vis serum K, the low AVP you also suffer would have a 'compensatory action' since AVP and Aldosterone have counter actions with Na & K preservation vs urination. I would encourage you to have true serum tests done though. Estimation from urine is always considered less accurate the massive levels of urination that occur with ME would greatly increase instrumental error. If you really are so low in both that would be more so the case for you.

I have to ask an obvious question here, has "diabetes inspidus" been ruled out? This does occur with some ME patients (in milder form) if you had zero 24 hour AVP true diabetes inspidus would be much more likely and it's a life threatening disease.. If your body were trying to produce AVP and preserve K (but failing), that could well cause mayhem with other hormones in order to preserve blood pressure.

Please also clarify are ALL of your catechols high or just NE?

If the 24 hour levels of both hormones are as low as your test indicates you need to see a qualified doctor about this rapidly and arrange a water deprivation test. I cannot stress that enough. That test result worries me greatly.

Had anybody else here come across an ME patient with such low levels of both Aldosterone and AVP?

 

[JBB]

I'm going to throw in my 2 cents here. @leokitten I really admire all the research you've done and the systematic approach you are taking to figuring out the cause of this horrific illness. I thought I'd done a fair amount but nothing in comparison!

I know I'll get shot down here but this is just my experience after 5 years of being ill. I have tried most of the things (also most probable to me) on your original list you put together. Interestingly the only thing I have found to help is good sleep combined with 9-5 rest in which time I usually do a fair amount of meditation lying down. Meditation changes the balance of the sympathetic and parasympathetic nervous system (you can find validation of this) and I wonder if I can put my short remissions down to this. They always occur when I have good sleep and rest + meditation. Maybe this is enough to swing the balance back in our favour if it were kept it up long enough.

I appreciate everyone is different but I just thought I'd throw this it in the pot! I definitely feel meditation has been one of the only things to help me. The other being IV magnesium which, after an initial amazing effect, gradually did nothing after a week. Continued this for 3 months nearly every day 200mg elemental mg IV but no effect. In fact after this my intracellular mg was still very low.

Best wishes,

JBB

 

[leokitten]

Hi everyone,

I have a major update on this topic, apologies for not writing sooner it took many months to figure out what has been going on.

I was able to get my blood volume measured accurately by Daxor BVA-100 machine and radioisotope method twice at two different locations over a month apart and the results were completely unexpected. I did it the second time over a month after at a different hospital because the first results were so shocking.

My plasma volume is in extreme excess, i.e. I have hypervolemia. This is completely opposite of what I expected and after experiencing many symptoms that people who believe they have low blood volume have I would say you cannot know at all based on symptoms alone, you must get the Daxor blood volume analysis test in order to definitively know what is your blood volume status is. Also I've never taken any blood volume enhancers because after trying things like desmopressin, florinef, and IV saline they just made me feel worse right away so I stopped a long time ago.

If ME/CFS caused you to have the following symptoms (as it did with me):

• A generally lowered heart rate than you had before the disease with only some periods of tachycardia
• Higher blood pressure than you had before the disease
  
• A bounding pulse, you feel your heart beating hard and at time with each pulse the blood movement actually shakes your head or upper body
  
• Polyuria, i.e. increased urination, at least for many months to a year or more in the beginning of the disease
  
• Low ADH/vasopressin and low aldosterone
• Swelling in the abdomen (which might feel like gastrointestinal)
  
• Dizziness

ALL of the above symptoms could be a result of excess plasma volume.

• Your body will lower your heart rate in response to hypervolemia and you will get a bounding pulse.
• Your blood pressure when there is excess blood volume.
  
• Your body will attempt to correct the excess plasma volume by reducing your ADH/vasopressin and aldosterone levels causing your kidneys to pump out a lot of urine.
  
• You will get abdominal swelling as another response by your body to correct the hypervolemia and move excess water out of your vascular system and into tissues.
• Severe hypervolemia will also cause reduced tissue oxygenation just like hypovolemia, causing dizziness and other symptoms.

So some or many of us with ME/CFS have excess blood volume even though some symptoms might feel like low blood volume, you must get the Daxor blood volume analysis test in order to definitively know what is your blood volume status is.

Also this means those of you who thought you had this mild-to-moderate diabetes insipidus (which I did see my posts) it could be completely wrong, it could be your body trying to respond to excess plasma volume!

After knowing I have hypervolemia I was referred to a cardiologist, hematologist, and nephrologist to do all these tests and procedures to discover why I had hypervolemia. The medical literature states that you essentially get hypervolemia because of three major reasons:

1. Heart failure or other heart-related problems
   
2. Kidney failure or other kidney-related problems
   
3. Excess protein in the blood (excess antibodies i.e. immunoglobulins or other e.g. albumin)

I went through every relevant blood test, MRI, and ultasound and told they cannot find what is wrong and causing the hypervolemia, they are completely baffled. With the data they have my heart, kidneys and blood were perfectly normal. I was thinking it would be #3 because of the high antibody titers to intracellular pathogens commonly found in ME/CFS which I have but no they said I don't have excess proteins in my blood (which would cause water to be sucked from tissues into blood stream).

Anyway, all this has been disheartening because everything with this disease involves so much effort to find answers and always ends up with doctors completely at a loss.

I put this post into its own thread:
People with ME/CFS can have hypervolemia and not low blood volume

 

[Leopardtail]

Hi everyone,

I have a major update on this topic, apologies for not writing sooner it took many months to figure out what has been going on.

I was able to get my blood volume measured accurately by Daxor BVA-100 machine and radioisotope method twice at two different locations over a month apart and the results were completely unexpected. I did it the second time over a month after at a different hospital because the first results were so shocking.

My plasma volume is in extreme excess, i.e. I have hypervolemia. This is completely opposite of what I expected and after experiencing many symptoms that people who believe they have low blood volume have I would say you cannot know at all based on symptoms alone, you must get the Daxor blood volume analysis test in order to definitively know what is your blood volume status is. Also I've never taken any blood volume enhancers because after trying things like desmopressin, florinef, and IV saline they just made me feel worse right away so I stopped a long time ago.

If ME/CFS caused you to have the following symptoms (as it did with me):

• A generally lowered heart rate than you had before the disease with only some periods of tachycardia
• Higher blood pressure than you had before the disease
  
• A bounding pulse, you feel your heart beating hard and at time with each pulse the blood movement actually shakes your head or upper body
  
• Polyuria, i.e. increased urination, at least for many months to a year or more in the beginning of the disease
  
• Low ADH/vasopressin and low aldosterone
• Swelling in the abdomen (which might feel like gastrointestinal)
  
• Dizziness

ALL of the above symptoms could be a result of excess plasma volume.

• Your body will lower your heart rate in response to hypervolemia and you will get a bounding pulse.
• Your blood pressure when there is excess blood volume.
  
• Your body will attempt to correct the excess plasma volume by reducing your ADH/vasopressin and aldosterone levels causing your kidneys to pump out a lot of urine.
  
• You will get abdominal swelling as another response by your body to correct the hypervolemia and move excess water out of your vascular system and into tissues.
• Severe hypervolemia will also cause reduced tissue oxygenation just like hypovolemia, causing dizziness and other symptoms.

So some or many of us with ME/CFS have excess blood volume even though some symptoms might feel like low blood volume, you must get the Daxor blood volume analysis test in order to definitively know what is your blood volume status is.

Also this means those of you who thought you had this mild-to-moderate diabetes insipidus (which I did see my posts) it could be completely wrong, it could be your body trying to respond to excess plasma volume!

After knowing I have hypervolemia I was referred to a cardiologist, hematologist, and nephrologist to do all these tests and procedures to discover why I had hypervolemia. The medical literature states that you essentially get hypervolemia because of three major reasons:

1. Heart failure or other heart-related problems
   
2. Kidney failure or other kidney-related problems
   
3. Excess protein in the blood (excess antibodies i.e. immunoglobulins or other e.g. albumin)

I went through every relevant blood test, MRI, and ultasound and told they cannot find what is wrong and causing the hypervolemia, they are completely baffled. With the data they have my heart, kidneys and blood were perfectly normal. I was thinking it would be #3 because of the high antibody titers to intracellular pathogens commonly found in ME/CFS which I have but no they said I don't have excess proteins in my blood (which would cause water to be sucked from tissues into blood stream).

Anyway, all this has been disheartening because everything with this disease involves so much effort to find answers and always ends up with doctors completely at a loss.

I put this post into its own thread:
People with ME/CFS can have hypervolemia and not low blood volume

Are you saying that many of us do or may have high blood volume?

 

[leokitten]

Are you saying that many of us do or may have high blood volume?

I have ME/CFS (flu-like onset, severe immune dysfunction with extremely high titers of EBV, CMV, HHV-6, M. pneumoniae, autonomic dysfunction, exercise intolerance, gastrointestinal problems, and so many other physical symptoms) and I've had my blood volume measured twice using the most accurate method available and the results show that my blood volume is too high. In addition as mentioned in the post many of my lab results and symptoms can be explained by too high blood volume.

So short answer is yes, I'm one example so I'm sure there are others.

Doctors ruled out the most likely causes of high blood volume: heart failure or related issues, kidney failure or related issues, and hematological abnormalities. If you have a chance to read the other thread where I moved this post other people mentioned that there can be a fourth cause which is the autonomic dysfunction.

Autonomic dysfunction can cause blood volume control to fail and it seems it can fail in either direction. And I believe this big relative shift in one's blood volume really causes a lot of ME/CFS symptoms, to live with chronic hypervolemia or hypovolemia causes a huge physiological stress on your body, organs, tissues, etc. If we can correct this and accurately measure that it is corrected we will improve our lives.

 

[Tired of being sick]

Is ME/CFS caused by biological stress and perpetuated by high catecholamines and low blood volume?
.

Whoa!
Your thread title is basically describing the Hyperadrenergic form of POTS..

the hyperadrenergic form of POTS, is related to increased amount of catecholamines, that increase the blood pressure upon standing. [3]

Some positive for POTS patient's BP steadily rises to or above 140/90
along with excessive increase of plasma norepinephrine.
This is POTS with a Hyperadrenergic response causing hypertension..
I call this my fight or fight adrenal action.
This gives me incredible strength for a short short period of time
with instant fall hard and crash afterwards..

The cause is LOW BLOOD VOLUME........