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johnlawrenceaspden comments on The Thyroid Madness : Core Argument, Evidence, Probabilities and Predictions - Less Wrong Discussion

10 Post author: johnlawrenceaspden 14 March 2016 01:41AM

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Comment author: johnlawrenceaspden 16 March 2016 05:13:36PM *  0 points [-]

No worries about sounding harsh! I declared Crocker's Rules, so I'm explicitly asking you to optimise for communication and not worry about offending me. And I very much appreciate you taking the time to tell me things I don't know.

I'd be surprised if pig's thyroid cured a mitochondrial myopathy.

That's exactly what I'm saying! The action of T3 seems to be to control ATP recycling in the mitochondria. Sarah Myhill's beautiful paper to my mind proves almost beyond doubt that that's the problem in CFS. This is what I mean by 'every time I look for disconfirming evidence, I find new reasons to believe'.

I know that I sound like a crank. That's because I am a crank. I am a member of several at-risk groups for Arrogant Overconfidence Disorder, which I strongly suspect to be related to hypothyroidism in some way. Others have suggested that I am under a certain amount of 'stress'.

CFS/FMS and hypothyroidism are much more similar than most diseases, to the point where out of a fabulous number of possibilities I was trying to fit to what was wrong with me, hypothyroidism looked instantly like what I had, despite the fact that I'd not only had the test for it, but the test was bang in the middle of the normal range. And I think the CDC agree. One of the diagnostic criteria is explicitly that hypothyroidism have been ruled out (haven't checked this, just a memory).

But also, doesn't the fact that all diseases look similar strike you as suspicious? As I understand it that was the whole reason for the 'stress' theory in the first place.

Let me think about the logic for a while, I'll get back to you.


OK, logic looks fine. I really need to know if that bit's wrong. It means my mind is broken.

If they're not differently caused then they have the same cause. And if that's true, then in one case the TSH test is picking it up, and in the other it's not. So the test is not doing what it's supposed to.


Suppose diabetes was diagnosed by insulin levels instead of blood glucose. And there were two sets of patients, who had roughly the same symptoms, but one lot weren't treated because the insulin test showed that their problems weren't diabetes.

Would you not say that the insulin test was broken?

We should be looking for the 'blood glucose' for hypothyroidism. And as a very lot of people have been claiming since 1940, that's 'slow metabolism'.


I really hate arguing by analogy. But it seems people don't understand unless I do, and I'm now arguing to persuade. Not of the truth of the hypotheses, but of their plausibility.

The sciences I trained for would leap on this. Medical Science has left it uninvestigated (to say the least) since 1970. Whether I'm right or not, that's careless.

And if I'm right.... Jesus Christ.

Comment author: pianoforte611 17 March 2016 02:20:04AM 1 point [-]

It seems I somewhat misunderstood your argument and misjudged you; I tentatively pegged you as a pig’s thyroid evangel feigning humility. I apologize. I also apologize because I am not the opponent you are looking for.

Since I apparently didn’t stress this enough, I will conclude by saying again that without interventional data, you have nothing. It doesn’t matter how beautiful your theory is, it doesn’t matter how smart you are, if it disagrees with experiment then its wrong. Repeating your hypothesis again and again, doesn’t help your case, it hurts your credibility. Unfortunately this is all I have to offer that I think is worth offering at this point.

Comment author: Lumifer 17 March 2016 03:16:54PM 1 point [-]

without interventional data, you have nothing

That is not true. You would prefer to have data from randomized intervention trials, but even without them you can look and collect data and come to conclusions.

Comment author: johnlawrenceaspden 17 March 2016 02:42:48PM *  0 points [-]

My dear old thing! That is a perfectly natural assumption to make and there is no need to apologise. If I were convinced of the truth of this idea, that is likely exactly what I would be, here practising the argument before I have to make it as a wild-haired prophet.

But I think I have managed to retain enough sanity to not want to believe it if it's not true. And I have pretty high standards for truth, and they definitely include intervention, cause, randomisation, placebos and control.

At the moment, I think that my hypotheses are probably false (because there is no way that I can see that it can be a widespread problem and yet fibro-turks are hot)

If it's false, then I think it's probably important to refute it properly if only to stop Wilson.

But I don't care very much about that. My own problems seem to be gone, they are or were probably either non-existent or horribly idiosyncratic and no one can help me with them, and I am just going to have to work it out on my own. That's a man's death and I am glad to have found a worthwhile enemy.

But I disagree with you about beautiful hypotheses. If they disagree with experiment then they are wrong, no question.

But they are worth looking at carefully, and a science that does not bother is not a science. And probably not truth-finding, even over the long run.

If you run into any interested opponents, do tell them there is someone wrong on the internet. There is still a mystery to explain! It's just back to being a hobby, for me.

Comment author: ChristianKl 16 March 2016 11:11:18PM 1 point [-]

But also, doesn't the fact that all diseases look similar strike you as suspicious?

Today we have people saying that cancer isn't a single illness and people trying to make distinction within broad categories of illnesses.

I think there's a good chance that depression isn't a single illness and a lot of our present disease categories aren't.

Comment author: Jiro 16 March 2016 10:11:44PM 1 point [-]

Suppose diabetes was diagnosed by insulin levels instead of blood glucose. And there were two sets of patients, who had roughly the same symptoms, but one lot weren't treated because the insulin test showed that their problems weren't diabetes. Would you not say that the insulin test was broken?

No, not in general. It might be for diabetes, but that's fact-specific. Let's try substituting in something else:

Suppose fractured skulls were diagnosed by X-rays. And there were two sets of patients, who had roughly the same symptoms (head pains and bleeding), but one wasn't treated because the X-ray test showed that their problem wasn't a fractured skull. Would I say that the X-ray test is broken? Of course not.

Comment author: johnlawrenceaspden 16 March 2016 11:27:44PM 0 points [-]

Nicely done, thank you! My brain is broken, and this "informal reasoning" is harder than it looks.

In your case, the X-ray test is doing its job perfectly. And if the posited type 2 hypothyroidism needs different treatment from the type 1 version, which it probably would, then the TSH test will be a great way to tell them apart.

What I don't think you're allowed to do is say 'no problem, can't be anything to do with your car crash' when what you mean is 'your skull is not fractured'.

So the TSH test is a great test for TSH, and probably a good test for circulating thyroid hormones (although it doesn't give the whole picture). But I don't think that means that the TSH test is a good test for 'no thyroid hormone-related problem'.

Do we still disagree? Can I phrase my A&B&C=>(D OR E) thing better? Or do I need to abandon it?

Perhaps: Hypothyroidism (by which I mean any failure of thryoid hormones to act on cells).....

Comment author: Jiro 17 March 2016 03:49:57AM 0 points [-]

What I don't think you're allowed to do is say 'no problem, can't be anything to do with your car crash' when what you mean is 'your skull is not fractured'.

That example only works because fractures are involved in a subset of car crashes and car crashes are involved in a subset of fractures; either one can happen without the other. If that relation doesn't hold true, you would be allowed to say that. For instance, saying "no problem, can't be anything to do with your car crash' when what you mean is 'you weren't anywhere near a car at the time of the crash'.

Comment author: johnlawrenceaspden 18 March 2016 05:31:50PM 0 points [-]

Agree again, thanks

Comment author: Lumifer 16 March 2016 05:50:39PM 1 point [-]

We should be looking for the 'blood glucose' for hypothyroidism. And as a very lot of people have been claiming since 1940, that's 'slow metabolism'.

Well, what's the test for speed of metabolism? Usually it's measured by the consumption of oxygen (VO2, high-level athletes do that a lot) and that's not a particularly expensive or difficult test. I am sure there is data on the distribution of VO2 in normal population. Do you think this test would be adequate for your purposes?

Comment author: johnlawrenceaspden 16 March 2016 06:14:38PM 0 points [-]

I think it most definitely would. Broda Barnes didn't like it, but only because the test is stressful and so tends to give false negatives (you're looking for the resting rate). But as long as it's done carefully, it should be fine.

Comment author: Lumifer 16 March 2016 06:59:41PM *  0 points [-]

The resting VO2 will need to be post-processed to be a diagnostic indicator. A brief look indicates that it is a function of sex (higher in men), age (higher in younger people), and weight. Might be a function of physical fitness (or at least lean body mass) as well.

Comment author: johnlawrenceaspden 16 March 2016 09:55:12PM 0 points [-]

Yes, sorry, thank you. The important quantity would be metabolic rate divided by the best prediction from the known relevant variables, as you say. It was once a test for hypothyroidism, so whatever the last word pre-blood test was should be good enough.

As I say, Broda Barnes found this test wanting and preferred waking axillary temperature (for females, on the correct days; for males, anytime), but it should be plenty good enough to establish that there's something funny going on. The problem is to draw the attention of medical science to it at all. I trust them to sort out the details.

Comment author: Lumifer 17 March 2016 02:56:07PM 0 points [-]

The problem is to draw the attention of medical science to it at all.

You are digging into this problem and I suspect there's enough published data on RMR (resting metabolic rate) in healthy and not-so-healthy people to collate some interesting evidence.

Comment author: johnlawrenceaspden 17 March 2016 03:12:20PM 0 points [-]

Agree, we should be able to refute it or strongly support it from the published literature. My initial attempts at that look like refutation. How can fibromyalgia in Turkish women be associated with HIGHER body temperature if my hypotheses are true?

And I wonder if there are enough Less Wrong readers with friends with these diseases to make a survey of some sort?

Comment author: ChristianKl 18 March 2016 12:45:02PM 0 points [-]

And I wonder if there are enough Less Wrong readers with friends with these diseases to make a survey of some sort?

That's not how you find patients a lot of patients. It makes more sense to seek online communitites where people with the illnesses congregate.

There's the patientslikeme forum: https://www.patientslikeme.com/forum/fibromyalgia/topics
http://www.fibromyalgiaforums.org/
http://www.healingwell.com/community/?f=24

Comment author: johnlawrenceaspden 16 March 2016 06:16:41PM 0 points [-]

Oh, and I predict that the resting VO2 would be normally distributed, but with a skew towards low values, and the size of that skew should be directly related to the size of the problem.

And that low VO2 should correlate strongly with cholesterol, fatigue, blah, blah, blah.

And I've got no idea whether that's true. It's a prediction.

Comment author: Lumifer 16 March 2016 07:16:23PM *  0 points [-]

I predict that the resting VO2 would be normally distributed

Well... Technically speaking, that's impossible because normal distribution is defined on the negative infinity to positive infinity range. So there should be some kind of a bounded bell-shaped distribution, might be a truncated normal but I have no idea whether to expect heavy or light tails.

A paper reports that for the sample size of 535 people they have the mean of 241 ml/min with the standard deviation of 56.6. They have some graphs and eyeballing them the observed minimum is around 100 and the observed maximum is about 450 -- that indicates a bit of a right-hand skew. But their population is not normal, their sample is basically cardiac patients.

You can go chase the references in that paper. At least one looks promising.