Phoenix Rising: The Gift That Keeps on Giving All Year Long
This holiday season Jody Smith turns her eyes to the people of Phoenix Rising and gives thanks for you all ...
Discuss the article on the Forums.

another autoantibody, HMGCR

Discussion in 'General ME/CFS Discussion' started by anciendaze, Dec 3, 2016.

  1. anciendaze

    anciendaze Senior Member

    Messages:
    1,806
    Likes:
    4,653
    This is a call for research help, not a definitive statement.

    Some time ago member SnowLeopard asked a question about possible rhabdomyolysis following exercise.

    Several of us told him this was a serious condition amounting to a medical emergency which could destroy his kidneys. He needed quick testing to tell if his colored urine showed actual breakdown of muscle fibers. Pogoman has since posted saying that a result of his own medical odyssey was a diagnosis of necrotizing autoimmune myopathy.

    Reading some papers on that illness raised questions in my mind about patients with the corresponding autoantibody who self-limit exercise to avoid the horrible effects of rhabdomyolysis bad enough to produce colored urine. (A patient I know with a different disorder producing rhabdomyolysis describes the feeling of "having muscles shredded", so it would not surprise me if he avoided exercise.) One distinctive feature I noticed was special weakness in large proximal muscles, which some patients I've talked to have reported without prompting.

    The autoantibody in question attacks the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). From a biochemical standpoint this is a particularly interesting enzyme. Treatments for this autoimmune illness are fairly new, but are possible.

    (Aside: pogoman's test for HMGCR antibodies was negative, but this is a new test and it is quite possible all relevant antibodies have not been covered. Consider how long it took to find antibodies to MuSK in patients with myasthenia gravis who met the clinical definition, but did not have the antibodies to nicotinic acetylcholine receptors.)

    Anyone who has recently reviewed citric acid cycle/Krebbs cycle/TCA cycle biochemistry will notice the central importance of acetyl-co A. The mevalonate pathway gets into a wide range of regulatory processes for metabolism, fatty acids and endocrine function. In terms of products affected we find cholesterol, steroids, heme and ubiquinones. This is suspiciously close to a number of pathways with anomalies found in many patients. One problem here is that we don't know which differences cause the pathology itself and which are attempts at compensation.

    Bad responses to statins are fairly common in the general population, but like many things these are more common among ME/CFS patients. I also note that doctors who have treated many such patients over a long period of time have remarked on the low incidence of atherosclerosis among them, which is surprising when you consider low levels of exercise. Impairment of the metabolic pathway producing cholesterol would explain both this finding and diffuse damage to nerves. (Cholesterol, including the "bad" form, is needed to build cell walls, and nerves have more cell surface area than most other types of cells.)

    Another aspect related to rhabdomyolysis is that, in those few extreme cases where ME/CFS patients die, kidney failure is often blamed, though this is usually considered the result of dehydration.

    If I were designing a chip with an array of tests for autoantibodies, a test for antibodies to HMGCR would be on the list. Declaring a problem psychosomatic without running such tests is irresponsible.

    A big problem with present-day medicine is that such a test is expensive, and is not run unless there are clear clinical signs suggesting such a problem. Waiting for a patient to produce colored urine indicating rhabdomyolysis before testing is not sound medical practice.

    Several other tests I would include are now done in paraneoplastic panels. Unfortunately, there are many doctors who feel you can't have a "real" paraneoplastic disorder unless you have cancer. Research publications show nearly half of those with the antibodies do not have detectable neoplasms. The devastating effects of such problems as an autoimmune response to NMDA receptors, N-type calcium channels or Ma2 make such illnesses worthy of treatment in their own right.
     
    moateyboatey, Cohen2, J.G and 12 others like this.
  2. kangaSue

    kangaSue Senior Member

    Messages:
    838
    Likes:
    912
    Brisbane, Australia
    Makes a mockery of the fact that symptoms indicative of a Paraneoplastic Syndrome can precede a cancer finding by up to 4 years (but more often a cancer is found within 18 months). Gastroparesis is one of the more common symptoms to precede a cancer finding but there are several antibodies in the Paraneoplastic Syndrome panel that can cause chronic GI dysmotility which can include some with IBS too.
    https://www.ncbi.nlm.nih.gov/pubmed/17918010
    https://www.ncbi.nlm.nih.gov/pubmed/21181442
     
    xrayspex likes this.
  3. anciendaze

    anciendaze Senior Member

    Messages:
    1,806
    Likes:
    4,653
    @kangaSue

    There is a fundamental source of "cognitive dissonance" here, should medical professionals ever look for such problems among their own cohorts. First, research studies now show that a non-negligible percentage of patients with both antibodies and symptoms never develop the expected detectable cancers, so you can't simply wait for this to resolve diagnostic errors. Second, problems like gastroparesis are unquestionably life-threatening, to say nothing of rhabdomyolysis. Third, the general response of doctors who feel they are dealing with psychiatric problems to the suggestion of running tests for paraneoplastic syndromes is "why would I do that, when I already have a solid diagnosis?" Fourth, once the problem is categorized as psychological the only threat to life is thought to be suicide.

    If anyone were thinking clearly, there would be careful testing of research cohorts to eliminate patients with paraneoplastic or other autoimmune disorders before attempting psychiatric intervention. This is practically never done. What happens instead is that patients go through years of useless treatments before anyone considers that they might have a physiological disease without simple clinical signs. (Check the case histories of those patients with cervical spinal stenosis recently discussed.)

    What about those patients who do develop cancers or other striking and life-threatening disorders? These are automatically reclassified as never having had "CFS" or whatever psychological label is favored. The definition of these illnesses as not life-threatening (except for suicide) is a tautology.

    Finally, what about suicidal patients who are placed in locked wards "for their own good"? The presumption here is that wise doctors know far better than the poor deluded patients what is going on. (Never mind that rates of undiagnosed physiological disease are always significant among long-term patients with serious psychological illness, or that life expectancy is often reduced by more than you would expect from common cancers, even after eliminating suicides.)

    As a check on the expertise of those "wise medical professionals" we might look at rates of suicide when they have similar problems. Unfortunately, this is as hard to document as rates of opioid abuse among medical professionals. My private sources indicate that both problems among medical professionals are much worse than among the general population. Anecdotal reports even say that the threat of commitment to a locked ward is more likely to precipitate suicide among those who are most knowledgeable about the subject.

    If that doesn't cause cognitive dissonance, it should.
     
  4. kangaSue

    kangaSue Senior Member

    Messages:
    838
    Likes:
    912
    Brisbane, Australia
    That went to a dark place @anciendaze, I take it you're getting sick of being screwed over by the medical profession too.

    It seems the more advances that are made in medical science, the more things stay the same. It's the old catch 22. It usually takes prompting by an informed patient to get the larger majority of medical professionals to go looking outside of the obvious, if you are lucky, but we as lay people don't know what we don't know until such time as one stumbles across these things in the likes of this forum.

    Oh, but don't mention you found it in an online forum as the perception is then that you are trying to find conditions to fit your symptoms so you're possibly a hypochondriac or a head case.
     
    Cohen2 and Sidereal like this.
  5. anciendaze

    anciendaze Senior Member

    Messages:
    1,806
    Likes:
    4,653
    @kangaSue,

    While there have been dramatic advances in the biological science underlying medicine, there has been remarkably little change in practice. Nothing in history compares with the flood of information obtained from sequencing genes, RNA and proteins. The amount of reliable objective information on human biology obtained in the last 25 years outweighs all previous data. This makes social experiments possible to see which aspects of medicine are based on the claimed solid research, and which are social constructs based only on shared opinions. Present indications are that opinions trump data.

    (Just as an example you might check long-term studies on prostate cancer and PSA tests. These indicated that tests were unreliable, and most surgical interventions actually increased mortality rates. Notice any change in practice?)

    Too much of this is concentrated as criticism of psychiatry, but the real problem is often with referring M.D.s. As I have told psychiatrists I know, the rest of the profession is using psychiatry as a wastebasket for unpromising cases that require too much time and thought. Those referring patients console themselves with the thought that psychiatrists are medical doctors too, and in principle can diagnose physiological disease. (This actually happened with a case of "stiff person syndrome" reported on this forum. That was an exception to common practice.) Psychiatrists save time by assuming the patient still has the option of being diagnosed with organic disease by their regular doctor, as if they didn't know this doctor will dismiss any symptoms without obvious clinical signs as psychosomatic. Amateur psychiatry is a real time and money saver for the bulk of the profession.

    Aside: you can find advice about avoiding unpromising cases in Hippocrates, who described diabetes mellitus quite clearly, then advised doctors to avoid these patients, who were going to die anyway.

    Incidentally, I will add at this point that feedback on this is broken. When I have followed a case history in which a patient was initially diagnosed with a psychiatric disorder, and this was later changed to a diagnosis of (often fatal) organic disease, more often than not the question "Did anyone bother to tell the psychiatrist who had been treating them?" is met with blank stares. Nor do psychiatrists whose patients disappear usually make efforts to discover what happened. There is a great deal of churn in psychiatry, as dissatisfied patients change doctors. Those with organic disease are frequently lost in the shuffle. Psychiatrists talk to other psychiatrists far more often than they talk to, say, oncologists. This is a systemic problem rather than a failure of individuals.

    When I recently expressed the opinion that significant change in medicine takes a generation because that is how long it takes doctors to retire or die and be replaced by those with different opinions, I was given the counterexample of treatment of ulcers. Unfortunately for this argument, that change only took 18 years, when the cause, helicobacter pylori, was known, and effective drugs were already on the shelf. Any one of thousands of doctors could have tried this treatment to check claims.

    It happened that my father had ulcers during this time, but was able to control them by sticking to a bland diet. One of his friends with ulcers had a vagotomy during this time, cutting the branch of the vagus nerve that goes to the stomach. When I told a friend about that, he asked, "Did it work?" My response was "The surgeon definitely got paid."
     
    ScottTriGuy and voner like this.
  6. kangaSue

    kangaSue Senior Member

    Messages:
    838
    Likes:
    912
    Brisbane, Australia
    Yep, the more things change, the more they stay the same.

    Don't start me on Psyches though. The best they could come up with recently was to offer me shock therapy because I tick their boxes for being depressed but don't tolerate antidepressants. I said I will agree to it as long as they are standing there holding my hand at the same time. Can't wait to read the report back to my G.P., once I go through the freedom of information bullshit and apply to find out what is being said about me that is as the assessment of you, the patient, is confidential between doctors.

    It goes without saying that unraveling complex biological system failures is far from easy but it never ceases to amaze me that while doctors can tell you with 100% certainly exactly what is not wrong with should you vary from the parameters of classic text book symptoms, have little input to offer as a plan in going forward.

    I'm at least glad that vagotomy is not something they routinely resort to anymore.
     
    ScottTriGuy likes this.

See more popular forum discussions.

Share This Page