Squirrel, it's bloody dangerous. I'm arguing that it should be investigated, not that everyone who feels tired should start glugging hormones.

But it's not unfounded. I've found loads of anecdotal and circumstantial evidence, and very little against (hot daytime fibro-turks is the most surprising thing, and the alternative people seem to think there's often also adrenal issues, but usually secondary). And now two studies from the 'proper' literature.

And I'm fairly sure that endocrinology has never bothered its pretty little head about type II versions, or the accuracy of its wretched TSH test, despite the example of diabetes staring it in the face.

I'm as sure as I can be without formal trial (so maybe about 25% confident?). But I'm now certain that the lack of investigation and of formal trials is inexcusable negligence. J' totally accuse.

The reason why Barnes' paper showing that desiccated thyroid lowering cholesterol levels and seeming to prevent cardiovascular disease isn't cited is because he was basically making his patients hyperthyroid. Lower cholesterol levels occur in hyperthyroidism.

There is a doctor I know of in California who gives his patients supra-physiological levels of T3 hormone (cytomel) to increase their metabolism, to help them lose weight, and to lower their cholesterol levels. It basically suppresses the thyroid's own production of hormone. In the short term, it works. It's brilliant. But it's crazy. We have no idea what the long-term consequences are. And since I'm pretty sure he's not running a study on it, we won't.

Hi, there can be all sorts of things going wrong! Mysterious resistances, gland failures, conversion disorders, broken pituitary, broken hypothalamus, faulty deiodinase enzymes, etc. All potentially inherited or acquired. We really do seem to have no idea how this complicated system works or what it's all for, or what can cause it to go wrong.

But I would have thought that if there was widespread 'central hypothyroidism', someone would have twigged by now, since that form does show up if you do a full panel of hormone tests.

Or I would have thought that when I wrote this. By now I am in such despair about the pitiful state of medical research that I wouldn't be surprised if they'd never thought to look, so maybe it is all just perfectly obvious from blood tests and the fools have ignored it.

And the question of 'what is the optimal treatment' is bound to be tricky. I'm just trying to demonstrate that the problems exist and are widespread and thus worth looking at!

Although Skinner certainly thought 'clinical hypothyroidism' could usually be fixed by bunging enough T4 at the problem. He does mention in his book that he sometimes used T3 or NDT, but he doesn't go into details. Various other people say 'mostly T4 with a bit of extra T3', but no-one has particularly clear ideas on what works and what doesn't or why.

Thanks for the reference to Ray Peat, I hadn't heard of him before. Can you link to the best expression of his thoughts?

That's interesting. In England and America I think that it would be illegal to sell desiccated thyroid as a prescription drug without a prescription. But it's perfectly legal to sell it as a food supplement. It's just dried bacon, after all.

It's quite difficult to find (people with TSH-detectable hypothyroidism get treated by their doctors with thyroxine, and for most people (~90%??) that seems to work perfectly), but it can be found.

I expect some fascist bastards will get round to outlawing that sooner or later. Before they do, we ought to find out whether it will cure CFS etc. After all, once it's illegal people will have to buy it from criminals, and I don't trust their quality control. Also it might put the price up slightly.

I'm interested in what the bad things that happened in France were. Obviously this is quite a potent drug, and so if it's for sale to the general public it is certain to cause harm from people taking far too much and overdosing.

But at the moment I think it's fairly safe in small doses for trial periods. And I'd very much like to know if that's not true.

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.