Well sure, and as an advocate of 'Traditional Western Medicine', I suppose I should be equally hurt by the disappearance of that once beloved (by doctor and patient alike!) treatment, so well supported by the humorous theories of Aristotle and Galen.

So I suggest that we appeal to Almighty God to show to us His Wille, by using the ritual of randomised controlled augury, as our fathers have shown us.

We should carefully select our patients using the strategems of Billewicz, and we should have three treatment arms, one with desiccated thyroid, one with leechwork and lancettry, and one with that flower of the modern schoole, graded exercise therapy.

I have a feeling that thryoid will come out well in the comparison. I am somewhat unclear as to GET vs leeches.

Let the best quackery win!

Actually I think it was only 'very hard' for GPs. It seems that most endocrinologists back in the day just ruled in or ruled out the obvious cases, and experimented with small amounts of thyroid on the rest. That doesn't look like a bad approach to me. Small amounts of thyroid with someone competent watching you won't hurt you.

Something like 'inadequate thyroid-hormone-mediated regulation of metabolism'.

Certainly that would include primary, secondary, and tertiary hypothyroidism, as well as the various forms of 'peripheral resistance', and the conversion disorders. (TSH probably detects the primary form. The question is 'how widespread are the other things.')

A good clinical correlate for all of those would probably be the Billewicz score from '68. Which he pretty much did work out by 'that which is made better by consuming desiccated thyroid'.

We might want to call all that 'easily-treatable clinical hypothyroidism', or 'twimbbcdt'. Congratulations, trope-namer!

But actually there are consistent reports of people with all the usual symptoms who don't respond to the sane use of T4/T3 or NDT, but who do improve on insanely high levels of T3.

So I'd actually want to draw 'hypothyroidism' a bit wider than "that which is made better by consuming desiccated thyroid".

And I bet you can get all sorts of 'dysthyroidism' too, where there are some resistant tissues but some are fine, and you or your system raises levels of this or that to compensate, and makes some bits of you hyper and some bits hypo at the same time.

If there's that, we might actually need to understand how it works to treat it. Imagine...

And then, I bet if there are two acquired hormone resistances then there are others, and I bet they're all horribly intertwined, and lots of nasty pathogens either taking advantage of or causing them, so there's probably a whole swamp of horrors that get a bit better with thyroid but that no-one would call 'hypothyroidism'. We'd probably need to call those 'acquired generalised hormone resistance disorders', which gives the pleasantly onomatopoeic "aghrd". And we're not going to nail those without actually rolling up our sleeves and playing around.

At the current rate of progress it should all be sorted out well after we've destroyed the universe by careless use of computers.

Unless it is all being caused by nasty chemicals in the environment, in which case we'll probably make ourselves so stupid that we just blunder straight back into Malthus' trap in a few generations. And that should sort it all out 'the natural way'

Actually I wrote back once you pointed that out, and we've swapped a few e-mails since, but now he's gone silent too. It is hard, this crankery.

I explained the whole bloody thing to him, with papers attached, and said:

What I would expect you to say is:

(a) We hear that all the time, and it's rubbish because [link]

(b) That's not a bad idea, but it can't be true because [implication that I have missed that isn't true]

(c) [redacted for fear of identifying correspondent]

and he said:

I [have specialised in a thyroid-related field but I don't see CFS patients] Therefore I have no experience nor opinion about the topic you want me to address.

Am I reading too much into this, or are those the words of a man trying not to get his name mixed up in a massive scandal? Are there in fact lots of people perfectly well aware that there is something dreadful going on but no-one wants to be the first to say it out loud in public?

This is absolutely evidence that huge doses of this stuff knacker your thyroid. But huge doses of most nasty chemicals probably do that. There's no particular reason to finger this as a significant cause unless it's in the environment in huge doses.

Agree with this too. On the one hand, Simpson's Paradox, on the other hand, Simpson's Paradox. But if you don't expect male/female confounder, it just gives you three goes at the magic p<0.05.

Frequentism. It's just broken.

Thank you so much, intelligent and careful criticism like this is exactly what I started posting on Less Wrong for!

Why is the Pollock trial evidence supporting your hypothesis?

Well, it's only fairly weak evidence, but it does seem that the healthy controls reacted differently to the patient group. What it really proves is that thyroxine isn't just a nice recreational drug that everyone likes. Healthy people dislike it. But it seems to have been less bad for the patients on average. So I imagine there were some people in the patient group who reacted well.

What I'm saying is that Skinner got strong evidence for the idea, and wanted it confirmed by PCRT (and I agree, that's necessary). So they did a PCRT, but not very well because they didn't find patients carefully. And yet they seem to have supported him anyway, but everyone thinks that they refuted him, because they didn't quite understand what he was saying.

What outcome from the trial would you have considered to be evidence against it?

If none of the patients had had any sort of thyroid problem, I'd have expected it to be equally bad for everyone. If that had been the result, then I'd have had to think that 'type 2 hypothyroidism' is rare, or that 'fixed doses of thyroxine don't fix it'. For a long time that's exactly what I did think! I was assuming you might need T3 as well and you might need to adust the ratio carefully. Skinner and Pollock together make me think that it might be fairly common, and mostly fixable with T4 alone.

Also, what part suggests that the healthy controls could distinguish the treatment from placebo? From Table 4, it seems that the reverse is true.

That shows that when they were asked which was the active preparation, they couldn't tell. They appear to have had a 'nocebo' effect, where they interpreted everything they felt as an effect of the drug. That's as expected.

What makes me think that they felt bad on thyroxine is table 2, where all the 'self-reported' psychological scores have got worse from thyroxine. In particular p=0.007 for the decline in Vitality. Since, as you point out, they really didn't know which was which, it's hard to see how they could have faked that.

At first glance, the results from that study look like straightforward evidence that this treatment is actively harmful.

Absolutely this treatment is harmful to healthy people. It should cause 'hypermetabolism', which is unpleasant. And severe hypermetabolism is awful. Very like the manic phase of manic depression. You should be careful not to give drugs to people who don't need them. That's why in the old days, if they weren't sure, they'd give you a bit and watch to see what effect it had. That was pretty much their test, except in the obvious cases.

but choosing a single dose is normal procedure.

Yes, but that does mean that anything that needs careful dose control will get rejected. In this case I think it might have made the treatment less effective, but it shouldn't have ruined it. I'm not making any criticism of the people who did this trial, I think it was a brave try and they did it well. I just don't think it's enough to refute Skinner. In fact I think it was supportive.

From what I’m reading I don’t think there is any recognized clinical diagnosis of hypothyroidism. The TSH test is the gold standard.

There was once. The paper:

STATISTICAL METHODS APPLIED TO THE DIAGNOSIS OF HYPOTHYROIDISM by W. Z. BILLEWICZ, R. S. CHAPMAN, J. CROOKS, M. E. DAY, J. GOSSAGE, SIR EDWARD WAYNE, AND J. A. YOUNG

was the last word in 'clinical diagnosis'. It was very very difficult to do, and GPs tended to refer suspected cases to experts. In doubtful cases they just tried treating it with small amounts of thyroid and checked that people improved rather than being made anxious and hyper.

The TSH test replaced that around 1970. But they never seem to have checked that clinical and biochemical diagnoses detected the same things, and after that there was the slow emergence of all sorts of nasty diseases that look very like hypothyroidism in the clinical sense but have normal TSH.

The TSH test seems to have been accepted (and then ruthlessly enforced) on the basis of theoretical arguments that weren't checked experimentally.

I do think that the TSH test detects gland failure quite well, in fact I think that if your thyroid gland gets destroyed, your TSH value will become huge. My (excellent) GP tells me that he sees people with TSH 30 with no symptoms at all (yet! Their thyroids are obviously on the way out...).

In fact the original 'normal range' for TSH was very wide indeed. And I think that's probably right too. Over the years the 'normal range' has got narrowed to the point where it's now so narrow people with abnormal TSH usually don't have any symptoms, and the noise in the test can put you outside the range. That's kind of weird. See recent AACB study where they thought the upper limit of normal should be 2.5.

There was a recent attempt to define a new clinical score (Zulewski et al), but the authors of the paper who'd constructed it refused to endorse it because the symptoms didn't correlate with TSH. That says to me that the test isn't detecting the disease it's supposed to detect.

You have the burden of proof

Absolutely accept that! And if Skinner was right, it should be dead easy to prove. Just re-run the Scottish trial using Billewicz as the entry criterion. It would be better if you could adjust the dose, but it should work quite well with a fixed dose, if you accept you're going to under-treat some people and over-treat others. Actually I'd rather use titrated doses of desiccated thyroid, since that's what they used to do, or T4/T3 combinations, but if I believe Skinner then they should all work, and it's just a question of which works best.

Could you summarize your support for this claim? Are these the only two peer-reviewed articles?

These are the only ones I can find through google scholar / pubmed. That in itself is really surprising and one of the things I can't explain! Why has such an obvious thing not been ruled out? Real doctors seem to try it all the time, find it works, and then get persecuted for trying it.

All the rest of it is anecdotal, from alternative sources, but there's a mountain of it. Just google. If people have tried this and it didn't work, they're keeping very quiet. All I've heard against is 'it helps, but it doesn't fix it entirely'. And the alternative people say exactly that themselves, and reckon that there's usually something adrenal going on as well.

I'd point primarily to Broda Barnes, John Lowe, Kenneth Blanchard, Gordon Skinner, Sarah Myhill, Barry Durrant-Peatfield, the various thyroid activist groups, Kent Holtorf, and 'Wilson's syndrome', off the top of my head, but there's plenty more where that came from. And a lot of those guys are actual medical doctors. The big exception is John Lowe, who was a chiropractor. But I've read a lot of his stuff and he was a very careful, thoughtful man.

90% of medical research findings are false

Indeed. The whole thing is a disaster. John Ioannides said 'Evidence Based Medicine Has Been Hijacked'. But I think it's worse than that. By saying that you're going to ignore the experience of doctors, and only accept very expensive evidence that can only be provided by wealthy sources, and even then using methods so bad that they're practically guaranteed to produce false answers, you've completely cut yourselves off from the truth.

I'd go further and say 'Evidence Based Medicine Has Been A Catastrophe'. I'm not more than half-convinced this thryoid-craziness is true, but I think the fact that it's never been properly investigated is a complete scandal.

I'm not against "evidence based medicine" because it's based on evidence. I'm against "evidence based medicine" precisely because it's based on ignoring most of the evidence. -- GK Chesterton's Homeopath.

I was helping a consultant friend revise for an interview the other day, and one of the practice questions was 'describe the hierarchy of evidence'. He put 'expert opinion' bottom.

Really? Forty years of experience in treating patients is less valuable than a single anecdote published in a journal? Really?

And of course, it doesn't actually work that way. The TSH test ruling out hypothyroidism is expert opinion. Its reliability is unfounded dogma. I can't find any evidence for it as the sole measure of thyroid system function at all.

I didn't know about all y'all. That's also pretty cool. Does "y'all" carry the implication "but not all y'all"?

A rabbi, a priest and a Bayesian walk into a bar. What's the probability this is a joke?

Your son will do well. Bloody school. Bloody homework.