I have a couple of questions about your hypothesis.
First, as I understand it, you are hypothesizing that there are people who have symptoms of CFS/etc. but normal blood levels of T3, T4, and TSH, who can nevertheless be helped by taking thyroid extract. And your hypothesized explanation for why these people are having symptoms of CFS/etc. is that, even though there are normal levels of T3 and T4 in their bloodstream, those hormones are not getting into their cells where they are actually needed. But if that is the case, how will putting more T3 and T4 into their bloodstream help? It still won’t be getting into the cells. It seems to me that, if your hypothesized cause were correct, the indicated treatment would be to somehow inject T3/T4 directly into the cells—or else to figure out what is blocking the hormones from getting into the cells, and fix that. But just putting more T3/T4 into the bloodstream, ISTM, should not work if your hypothesized cause were correct.
Second, as I understand it, you are taking the fact that treating these people with thyroid extract appears to help them, as evidence that your hypothesis is correct. But it seems to me that this fact is actually evidence for a different hypothesis: the hypothesis that the definition of “normal” levels of T3, T4, and TSH is incorrect. More specifically, that “normal” levels should be defined, not in a “one size fits all” fashion, but specifically for each person based on some set of factors that can vary from person to person. (Obvious candidates would be body weight/BMI and genetic factors.)
Hi Peter, I don’t want to claim credit for this, it’s mostly the work of John Lowe/Broda Barnes (and now Gordon Skinner). I’ve just put their ideas into what I think is a fairly compelling order, and connected them to some ideas of Greg Cochran and Sarah Myhill. I’m seeing myself more as a speaker for the dead.
I was definitely starting off thinking about ‘something wrong with those tests, a few cases missed, maybe’, and I absolutely agree that if we take the anecdotal evidence that T3/T4/NDT help in CFS at face value, then this is definitely evidence for that. Two different hypotheses can make a similar prediction.
I’ve ended up thinking about the ‘hormone resistance’ idea, because it seems like the sort of thing that might well be true, (once you’ve realised that it works that way in diabetes), and it’s the simplest explanation for what’s going on. Sometimes you’ll see people with symptoms and a TSH of 2, sometimes you’ll see people with a TSH of 30 (in whom something is obviously going wrong), but no symptoms at all yet.
As for ‘hormone resistance’ as an idea, you’re right that if the action of the hormones was completely blocked, adding extra stuff to the bloodstream wouldn’t make any difference. And also, those people should be very ill indeed with really obvious hypothyroidism. (Severe cases are easy to recognise).
But there’s no reason why resistance should be an on/off thing. There are all sorts of chemical reactions taking place between hormones in the blood and their effect on the mitochondria. All it would need is for something to mysteriously slow one of the reactions down.
John Lowe was forced into inventing the idea of ‘peripheral resistance to thyroid hormone’ by noticing that a lot (about 25%) of his patients didn’t get better (or in fact notice) his attempts to fix them with T4/T3. They should have been made quite ill by this if hormone deficiency wasn’t the problem. So he tried higher and higher doses of T3, and found that that worked. He never seems to have connected it to diabetes or to have wondered if it was present in the other cases. I think he thought that ‘central hypothyroidism’ was the principal problem (another thing that’s missed by TSH)
It would make sense as an immune response. Something nasty (virus most likely) might be trying to get into the cells, and in order to avoid being eaten alive, the body somehow tries to wall off the cells so it’s harder for things to get in and out. It’s a very scorched-earth defense, but those sorts of things happen. Often in bacterial diseases, your body takes most of the iron out of your bloodstream. That’s bad for you, but worse for the bacteria. Fever’s the same. It does you a lot of harm but it does the enemy more harm.
We have very little idea how the immune system works, or how pathogens try to get round it, but it’s a very strange and cruel world down there, and there’s group-selection on both sides, so I think it’s best viewed as a billion year war, with strategies, tricks, camouflage, and even cleverness involved.
Alternative medicine seems to be much more into the idea of ‘toxins’, by which they mean chemicals that weren’t around when we were evolving. That might well work too, but then you’d expect that there’d be a specific chemical which could reliably induce the resistance, and thus the symptoms of hypothyroidism. I don’t know of one.
Conventional medicine seems to mostly revolve around the idea of making up new chemicals and seeing what they do. And they seem to refuse to consider any evidence that doesn’t come from very careful formal trials (which are very expensive). I don’t think that’s a terribly good approach, myself, but it seems to be the best we’ve got.
All credit to them for wanting to avoid fooling themselves, but I think they’ve swapped ‘bad data’ for ‘no data’, when what they should have done is ‘been careful’.
I wish they’d spend more time thinking about cause and effect and what all these systems are ‘for’, and accepting that millions screaming in pain is not just a big placebo effect or a ‘psychological problem’
Ok, so the “hormone resistance” hypothesis is really something more like: the rate of some key reaction involving T3/T4 is being slowed down by some unknown factor; since we don’t know what the factor is, we can’t fix it directly, but we can increase the reaction rate by increasing the concentration of T3/T4 in the bloodstream to above normal levels, to compensate for the damping effect of the unknown factor.
This hypothesis makes an obvious testable prediction: that when people with CFS/etc. who are treated with thyroid extract feel better, the T3/T4 levels in their bloodstream should be above normal. Or, conversely, if their bloodstream T3/T4 levels are within the normal range, they should not feel better, even though they are being treated with thyroid extract. I don’t know if any existing data has this information.
Absolutely, hormone levels would have to be higher than they were, in order to make any difference.
Whether that means ‘out of the normal range’ for any particular hormone, I don’t know. Nobody seems to have the faintest idea what ‘normal range’ means for these things. But if there are serious cases of resistance, the level of the thing resisted should have to be way high in order to make any difference.
And it should probably cause TSH suppression. In my own case, I had TSH 2.51 when I first started complaining of symptoms, it was 4.06 when they came back, and with a tiny bit of thyroid which was nevertheless enough to get rid of all manifestations of CFS and cause some hyper symptoms it was 2.31, so looks like it pushed TSH down, but still not even as far as some people say is optimal.
And all of that could be noise in the test. Circadian cycle means TSH results can vary by a factor of two depending on when the blood is drawn. Go figure!
What would be ideal would be to figure out the cause of the ‘hormone resistance’, and fix it, rather than trying to overwhelm it.
It might even be a bad idea to fix it, if it’s performing some vital immune defence function.
Whether that means ‘out of the normal range’ for any particular hormone, I don’t know. Nobody seems to have the faintest idea what ‘normal range’ means for these things.
Yes, a better way to put it would be that the bloodstream levels of T3/T4 should be significantly higher when the person is treated and feels better than they were before treatment.
it should probably cause TSH suppression
That would be expected, yes.
What would be ideal would be to figure out the cause of the ‘hormone resistance’, and fix it, rather than trying to overwhelm it.
Yes, agreed. See below.
It might even be a bad idea to fix it, if it’s performing some vital immune defence function.
If this is true, it might also be a bad idea to overwhelm it. The “immune defense” hypothesis says that, if a person is feeling symptoms of CFS/etc., it’s because some pathogen is trying to attack their cells, so the immune defense kicks in, but as a side effect it also depresses normal cell metabolism. If thyroid therapy increases normal cell metabolism by overwhelming the immune defense, it might also increase the ability of the pathogen to infect cells. The only real fix in this case would be to find the pathogen and eliminate it.
Agreed. All I’m really saying is “For God’s sake, people, there’s enough evidence here to have a look, surely?”
We do have Broda Barnes’ word that taking desiccated thyroid long-term isn’t that bad for people. He really does seem to have put people on thyroid at the slightest excuse, and he reckoned that his patient records showed them being healthier than the general population, especially for things like heart disease. Which is kind of weird given that his patients were the sort of people who went to see a doctor and got put on lifetime medication.
Maybe only the really healthy could survive his methods and everyone else scurried back to more conventional doctors who would sensibly tell them it was all their fault for fancying their parents? Increasingly I think that psychiatry has the same advantage as homeopathy, in that it can’t possibly have any effect so they’re not going to hurt people.
I don’t know how seriously to take Barnes. Originally I thought he must have been a bit of a lunatic, until I ended up coming up with the idea above, which pretty much makes his observations as predictions. Then I read his book, and it said exactly what I thought it would say.
I disagree with his ‘origin story’, that the strange widespread hypothyroidism of modern times is because people aren’t dying of infections any more. (He thought that hypothyroid children were prone to infections and so they’d have all died of tuberculosis before they became adults. I think that a ‘genetic proneness to infection’ would have bred out very quickly.)
But again, if he was handing out thyroid meds to people who already had enough of the stuff naturally, that should have hurt them, not made them less prone to illness.
He might have been a fraud, but it seems a weird thing to do..… Even if he was just disregarding his patients’ complaints because he had given them thyroid and so they were damned well better, whatever they thought, he should have noticed them dying of heart attacks.
But I don’t really trust anyone medical any more. And Barnes was an endocrinologist.
I have a couple of questions about your hypothesis.
First, as I understand it, you are hypothesizing that there are people who have symptoms of CFS/etc. but normal blood levels of T3, T4, and TSH, who can nevertheless be helped by taking thyroid extract. And your hypothesized explanation for why these people are having symptoms of CFS/etc. is that, even though there are normal levels of T3 and T4 in their bloodstream, those hormones are not getting into their cells where they are actually needed. But if that is the case, how will putting more T3 and T4 into their bloodstream help? It still won’t be getting into the cells. It seems to me that, if your hypothesized cause were correct, the indicated treatment would be to somehow inject T3/T4 directly into the cells—or else to figure out what is blocking the hormones from getting into the cells, and fix that. But just putting more T3/T4 into the bloodstream, ISTM, should not work if your hypothesized cause were correct.
Second, as I understand it, you are taking the fact that treating these people with thyroid extract appears to help them, as evidence that your hypothesis is correct. But it seems to me that this fact is actually evidence for a different hypothesis: the hypothesis that the definition of “normal” levels of T3, T4, and TSH is incorrect. More specifically, that “normal” levels should be defined, not in a “one size fits all” fashion, but specifically for each person based on some set of factors that can vary from person to person. (Obvious candidates would be body weight/BMI and genetic factors.)
Hi Peter, I don’t want to claim credit for this, it’s mostly the work of John Lowe/Broda Barnes (and now Gordon Skinner). I’ve just put their ideas into what I think is a fairly compelling order, and connected them to some ideas of Greg Cochran and Sarah Myhill. I’m seeing myself more as a speaker for the dead.
I was definitely starting off thinking about ‘something wrong with those tests, a few cases missed, maybe’, and I absolutely agree that if we take the anecdotal evidence that T3/T4/NDT help in CFS at face value, then this is definitely evidence for that. Two different hypotheses can make a similar prediction.
I’ve ended up thinking about the ‘hormone resistance’ idea, because it seems like the sort of thing that might well be true, (once you’ve realised that it works that way in diabetes), and it’s the simplest explanation for what’s going on. Sometimes you’ll see people with symptoms and a TSH of 2, sometimes you’ll see people with a TSH of 30 (in whom something is obviously going wrong), but no symptoms at all yet.
As for ‘hormone resistance’ as an idea, you’re right that if the action of the hormones was completely blocked, adding extra stuff to the bloodstream wouldn’t make any difference. And also, those people should be very ill indeed with really obvious hypothyroidism. (Severe cases are easy to recognise).
But there’s no reason why resistance should be an on/off thing. There are all sorts of chemical reactions taking place between hormones in the blood and their effect on the mitochondria. All it would need is for something to mysteriously slow one of the reactions down.
John Lowe was forced into inventing the idea of ‘peripheral resistance to thyroid hormone’ by noticing that a lot (about 25%) of his patients didn’t get better (or in fact notice) his attempts to fix them with T4/T3. They should have been made quite ill by this if hormone deficiency wasn’t the problem. So he tried higher and higher doses of T3, and found that that worked. He never seems to have connected it to diabetes or to have wondered if it was present in the other cases. I think he thought that ‘central hypothyroidism’ was the principal problem (another thing that’s missed by TSH)
It would make sense as an immune response. Something nasty (virus most likely) might be trying to get into the cells, and in order to avoid being eaten alive, the body somehow tries to wall off the cells so it’s harder for things to get in and out. It’s a very scorched-earth defense, but those sorts of things happen. Often in bacterial diseases, your body takes most of the iron out of your bloodstream. That’s bad for you, but worse for the bacteria. Fever’s the same. It does you a lot of harm but it does the enemy more harm.
We have very little idea how the immune system works, or how pathogens try to get round it, but it’s a very strange and cruel world down there, and there’s group-selection on both sides, so I think it’s best viewed as a billion year war, with strategies, tricks, camouflage, and even cleverness involved.
Alternative medicine seems to be much more into the idea of ‘toxins’, by which they mean chemicals that weren’t around when we were evolving. That might well work too, but then you’d expect that there’d be a specific chemical which could reliably induce the resistance, and thus the symptoms of hypothyroidism. I don’t know of one.
Conventional medicine seems to mostly revolve around the idea of making up new chemicals and seeing what they do. And they seem to refuse to consider any evidence that doesn’t come from very careful formal trials (which are very expensive). I don’t think that’s a terribly good approach, myself, but it seems to be the best we’ve got.
All credit to them for wanting to avoid fooling themselves, but I think they’ve swapped ‘bad data’ for ‘no data’, when what they should have done is ‘been careful’.
I wish they’d spend more time thinking about cause and effect and what all these systems are ‘for’, and accepting that millions screaming in pain is not just a big placebo effect or a ‘psychological problem’
Ok, so the “hormone resistance” hypothesis is really something more like: the rate of some key reaction involving T3/T4 is being slowed down by some unknown factor; since we don’t know what the factor is, we can’t fix it directly, but we can increase the reaction rate by increasing the concentration of T3/T4 in the bloodstream to above normal levels, to compensate for the damping effect of the unknown factor.
This hypothesis makes an obvious testable prediction: that when people with CFS/etc. who are treated with thyroid extract feel better, the T3/T4 levels in their bloodstream should be above normal. Or, conversely, if their bloodstream T3/T4 levels are within the normal range, they should not feel better, even though they are being treated with thyroid extract. I don’t know if any existing data has this information.
Absolutely, hormone levels would have to be higher than they were, in order to make any difference.
Whether that means ‘out of the normal range’ for any particular hormone, I don’t know. Nobody seems to have the faintest idea what ‘normal range’ means for these things. But if there are serious cases of resistance, the level of the thing resisted should have to be way high in order to make any difference.
And it should probably cause TSH suppression. In my own case, I had TSH 2.51 when I first started complaining of symptoms, it was 4.06 when they came back, and with a tiny bit of thyroid which was nevertheless enough to get rid of all manifestations of CFS and cause some hyper symptoms it was 2.31, so looks like it pushed TSH down, but still not even as far as some people say is optimal.
And all of that could be noise in the test. Circadian cycle means TSH results can vary by a factor of two depending on when the blood is drawn. Go figure!
What would be ideal would be to figure out the cause of the ‘hormone resistance’, and fix it, rather than trying to overwhelm it.
It might even be a bad idea to fix it, if it’s performing some vital immune defence function.
Yes, a better way to put it would be that the bloodstream levels of T3/T4 should be significantly higher when the person is treated and feels better than they were before treatment.
That would be expected, yes.
Yes, agreed. See below.
If this is true, it might also be a bad idea to overwhelm it. The “immune defense” hypothesis says that, if a person is feeling symptoms of CFS/etc., it’s because some pathogen is trying to attack their cells, so the immune defense kicks in, but as a side effect it also depresses normal cell metabolism. If thyroid therapy increases normal cell metabolism by overwhelming the immune defense, it might also increase the ability of the pathogen to infect cells. The only real fix in this case would be to find the pathogen and eliminate it.
Agreed. All I’m really saying is “For God’s sake, people, there’s enough evidence here to have a look, surely?”
We do have Broda Barnes’ word that taking desiccated thyroid long-term isn’t that bad for people. He really does seem to have put people on thyroid at the slightest excuse, and he reckoned that his patient records showed them being healthier than the general population, especially for things like heart disease. Which is kind of weird given that his patients were the sort of people who went to see a doctor and got put on lifetime medication.
Maybe only the really healthy could survive his methods and everyone else scurried back to more conventional doctors who would sensibly tell them it was all their fault for fancying their parents? Increasingly I think that psychiatry has the same advantage as homeopathy, in that it can’t possibly have any effect so they’re not going to hurt people.
I don’t know how seriously to take Barnes. Originally I thought he must have been a bit of a lunatic, until I ended up coming up with the idea above, which pretty much makes his observations as predictions. Then I read his book, and it said exactly what I thought it would say.
I disagree with his ‘origin story’, that the strange widespread hypothyroidism of modern times is because people aren’t dying of infections any more. (He thought that hypothyroid children were prone to infections and so they’d have all died of tuberculosis before they became adults. I think that a ‘genetic proneness to infection’ would have bred out very quickly.)
But again, if he was handing out thyroid meds to people who already had enough of the stuff naturally, that should have hurt them, not made them less prone to illness.
He might have been a fraud, but it seems a weird thing to do..… Even if he was just disregarding his patients’ complaints because he had given them thyroid and so they were damned well better, whatever they thought, he should have noticed them dying of heart attacks.
But I don’t really trust anyone medical any more. And Barnes was an endocrinologist.