Posts

Coronavirus Transmission 2020-10-29T11:31:04.800Z
The Thyroid Madness: Two Apparently Contradictory Studies. Proof? 2016-04-10T20:21:52.596Z
In Defence of Simple Ideas That Explain Everything But Are Wrong 2016-03-22T15:46:57.542Z
The Thyroid Madness : Core Argument, Evidence, Probabilities and Predictions 2016-03-14T01:41:35.900Z
Thyroid Hormones, Chronic Fatigue and Fibromyalgia: A Hypothesis and a Proposed Experiment 2016-02-20T23:20:18.665Z
A Medical Mystery: Thyroid Hormones, Chronic Fatigue and Fibromyalgia 2016-02-14T13:14:01.258Z
Truth Tables 2013-12-12T22:16:00.190Z
What's the Value of Information? 2012-08-29T16:20:59.210Z

Comments

Comment by johnlawrenceaspden on A Semitechnical Introductory Dialogue on Solomonoff Induction · 2021-09-19T17:22:08.498Z · LW · GW

We can also consider it as a probability distribution over infinite sequences

 

Surely, 'over finite sequences'?

Comment by johnlawrenceaspden on Great Negotiation MOOC on Coursera · 2021-08-24T11:35:50.375Z · LW · GW

That would probably be true of Yale's maths course, if they started from the beginning. It probably is true of Yale's computer science course.

Comment by johnlawrenceaspden on Great Negotiation MOOC on Coursera · 2021-08-24T11:34:10.590Z · LW · GW

I've been a freelance my whole life, am often involved in negotiations of one sort or another and I have learned interesting things from just the first week of this course. I am sure they will come in handy in future.

I agree that a smart ten year old could probably follow it, but that's the sign of something being really well explained, not that it's trivial. There's actually some deepness here.

I intend to do the rest of it. If anyone in Cambridge, UK is interested, get in touch (07943) 155029 and let's do the two-man exercises in person over coffee.

Comment by johnlawrenceaspden on The Thyroid Madness : Core Argument, Evidence, Probabilities and Predictions · 2021-08-21T17:40:54.192Z · LW · GW

Hi Jane, in short, my plan to fix a disease I'd made up myself by ordering dodgy drugs off the internet worked perfectly, and I haven't thought of myself as ill for the last five years. I still take thyroid daily though, and I can't give it up without getting the CFS symptoms back. 

I've no idea what was ever wrong with me, or whether it's still wrong or got better on its own years ago, but I'm totally convinced that thyroid drugs fixed it or at least made it tolerable. My TSH is almost always suppressed, i.e. 0, and my free T4 and T3 levels are usually at the high end of the normal range. Any doctor worth his salt is going to tell me to drop my thyroid dose with those readings, and they do, but if I try I just feel awful for a bit, and all the old symptoms come back until I put it up again. I have absolutely no symptoms of hyperthyroidism/thyrotoxicity at my happy dose. 

But sadly, I know of at least a couple of CFS patients who've tried it in good faith (one was a close friend at the time I was working all this out five years ago, who came down with CFS a couple of years ago) and not had it work. All they report is a feeling of overstimulation, like with caffeine, and neither of them continued with it. My experience was more like a sudden miraculous unambiguous fix.

So your mileage may vary, but try it anyway. CFS is awful, thyroid's not too dangerous.

The best book I read was Gordon Skinner, 'Diagnosis and Management of Hypothyroidism'. John Lowe's book 'The Metabolic Treatment of Fibromyalgia' was also very good. Unsurprisingly they give conflicting advice and are both out of print. Everything else has at least a bit of bullshit in it. Mind how you go and good luck!

I should probably do a follow up post, five years on. 

 

Coronavirus-wise:

Recently, my coronavirus vaccine jabs (AstraZeneca), brought on bad fatigue and listlessness, the first one for a week, the second one for more like two months. Normally if I feel fatigued I put my thyroid dose up a bit and it goes away, so I tried that, but all it did was make me anxious and hot, as well as fatigued and listless, so I put it back down again. 

That was the most severe reaction of anyone I know to the vaccines. Lots of people get fatigue for a week, but two months is pretty much unheard of I think.

The fatigue seems to have finally cleared now, and I'm back to feeling as bouncy as before on the same dose of thyroid as I was originally on.

I asked on both reddit's r/hypothyroidism and on r/cfs, and I got a couple of replies on r/hypothyroidism saying that they'd had no such effect. And three on r/cfs saying that they'd all had something similar.

I have a feeling that the tiredness is something to do with the innate immune response trying to shut the body down to deny resources to viruses, and I wonder if that response gets stuck on, either by accident, or because you don't really clear the virus (like with the herpesviruses).

Best of luck on your journey, and I hope you find your miracle like I did. Most CFS just gets better on its own eventually I think, so hang on in there. But that doesn't mean that it's not worth trying the cheap, safe things that various loonies like me reckon might help, just in case they do!

Comment by johnlawrenceaspden on Curing insanity with malaria · 2021-08-04T18:06:05.601Z · LW · GW

I remember reading about this years ago and wondering, if it was the heat that killed the syphilis, why they couldn't just use total immersion in hot baths to raise core temperature (more) safely and in a more controlled manner. 

It sounds like it was tried, any idea why it didn't work?

Comment by johnlawrenceaspden on Covid 7/29: You Play to Win the Game · 2021-07-29T17:26:51.845Z · LW · GW

Hi Zvi, you've got plenty of money and I'm really mean. Is it OK if I pay you in strong upvotes? Especially for that last bit, which is just kind of hilarious throughout.

Comment by johnlawrenceaspden on Social media: designed to be bad for you & for society · 2021-07-24T19:45:11.691Z · LW · GW

This all seems obviously correct to me, and good reason to worry about engaging with such things. I've never liked advertising of any kind, and crossing advertising with addictive apps just looks terrible.

Comment by johnlawrenceaspden on Covid 7/15: Rates of Change · 2021-07-19T12:11:27.028Z · LW · GW

The first thing about this pandemic that's really confused me is: India is going full hockey-stick -> the death rate is suddenly falling in India.  Do you know why that was? 

Comment by johnlawrenceaspden on Going Out With Dignity · 2021-07-10T17:32:46.167Z · LW · GW

It is not obvious at all that 'AI aligned with its human creators' is actually better than Clippy.

It's pretty obvious to me, but then I am a human being. I would like to live in the sort of world that human beings would like to live in.

Comment by johnlawrenceaspden on Going Out With Dignity · 2021-07-10T17:31:49.838Z · LW · GW

Since I read The Basic AI Drives, I have known abstractly the world is doomed. Though my system 1 seems to have difficultly comprehending this, this belief implies I, and everyone and everything I love, am doomed, too.

This has always been true. This too will pass. AI makes it happen faster, is all. 

And not to worry; as someone apparently once wisely said: "I was dead for billions of years before I was born, and I have never suffered the slightest inconvenience from it."

Sure, maybe we can fix it. But it looks highly non-trivial.

Comment by johnlawrenceaspden on Don't feel bad about not knowing basic things · 2021-06-03T10:16:55.853Z · LW · GW

Sorry, obvious to a mathematician who thinks about dz/dt=iz and realises that "exponentiation is time-evolution". At that point it's just "if you rotate for just long enough to turn half-way round, you'll be pointing backwards".

Comment by johnlawrenceaspden on Don't feel bad about not knowing basic things · 2021-06-03T10:13:48.875Z · LW · GW

Still don't really understand what a semi-group is (something something exponential).

Then perhaps this was a little hyperbolic?

Comment by johnlawrenceaspden on A Medical Mystery: Thyroid Hormones, Chronic Fatigue and Fibromyalgia · 2021-05-31T14:31:59.773Z · LW · GW

Oops, went to post this paper on my little subreddit and it's already there! There's quite a lot of this sort of stuff in the literature, what we need is someone to give it a go in a proper trial and work out whether it really helps. I'm sure that it will work for some people, I'm fairly sure that it won't work for everyone. 

If I take Gordon Skinner seriously, then a good 'diagnosis of hypothyroidism by symptoms' should be what would tell you in advance whether it would work or not. But honestly, if you're careful enough that you can try this on yourself without doing harm, just give it a go. Do tell your doctor what you're doing. He'll tell you not to, but he can keep an eye on you while you do it anyway.

Comment by johnlawrenceaspden on A Medical Mystery: Thyroid Hormones, Chronic Fatigue and Fibromyalgia · 2021-05-31T14:20:12.978Z · LW · GW

Thank you, that is most interesting! I wouldn't call this nearly conclusive evidence, but I would certainly call it further weak evidence to stick on the pile. 

My favourite in this line is Gordon Skinner's paper "Clinical Response to Thyroxine Sodium in Clinically Hypothyroid but Biochemically Euthyroid Patients".

https://www.tandfonline.com/doi/abs/10.1080/13590840050043530

I did once make a subreddit devoted to this sort of thing:

https://www.reddit.com/r/thethyroidmadness/

and stuck everything I found on it, but it's drawn remarkably little interest. I'll read this nice new paper and add it there.

But you want to hear about my own experiences, so:

In short, thyroid's been an almost perfect fix for me ever since I
wrote all that, so much so that I've lost interest in the subject. I
currently take 100ug of T4 and 1 grain of NDT every day, and that's
been fairly stable for around four years now.

My TSH is almost always suppressed (i.e. 0), but my only health
problems are sports injuries, and I don't have any of the symptoms of
hyperthyroidism.

I don't feel *perfectly* well, occasionally I feel a bit more tired
than seems reasonable, and sometimes I get depressed for no good reason, but usually fiddling around with the dose seems to sort that out.  (too hot, down a bit, too tired/sad, up a bit)

I've never gone back to being the bouncy energetic person I was in my thirties, but it's nothing compared to the living hell of chronic fatigue syndrome. I play tennis three times a week and cycle to my office every day.

However, I do know two or three people who had something CFS-like and
bought my arguments and tried thyroid to fix it, and all they got was
a feeling of overstimulation, like drinking far too much coffee, and
they didn't think it was worth sticking with. So it clearly won't fix everybody or even a plurality of CFS people.

That wasn't my experience, for me it was an excellent instant fix for
everything that was wrong with me. Too good to be true.

So my advice is to give it a go. It probably won't work, but you
should be able to tell easily if it's going to work for you. Be
careful though, do the research and try very small doses of NDT at
first.

Comment by johnlawrenceaspden on Don't feel bad about not knowing basic things · 2021-05-24T12:41:45.156Z · LW · GW

So the idea is that if you've got a linear differential equation, like dx/dt=2x, then all the solutions look like x=x0*exp(2t).

And you could imagine that there's an operator which says "Where will this point end up in 1 second?", call it O(1), which looks like x0->x*exp(2). I.e. it just gets multiplied.  

If you know that operator, then you know the operator that represents "Where will the point end up in 2 seconds", because you can say "where will it end up one second later" then "where will that point end up in another second. 

 So this gives you a law that O(2) is O(1) done twice. And O(3) is O(2) followed by O(1). So these operators are a group (the identity is 'where will it be after I run the equation for no seconds').

In the one-dimensional ODE case, this is all so trivial that it's not worth mentioning. Almost a pun. 

But it generalises nicely to dx/dt=Ax, where x is a vector and A is a matrix, and that gives us a way of defining exp(At), i.e., how to exponentiate a matrix, by saying, "well what if we run this matrix equation for a second and see where it puts all the vectors?"

And in fact we can generalize it further, to differential equations on linear operators on infinite-dimensional spaces. Which is another way of looking at partial differential equations. (A function is an infinite dimensional vector, a vector is a function on a finite set). 

So you can talk by analogy about how to exponentiate the diffusion equation, and a time delay operator that takes wiggly functions to less wiggly functions. 

But you can't always run pdes backwards, e.g. the diffusion equation won't run in reverse, so you don't always get a full group. 

I think that's the intuition for semigroups, I hope that's what you were talking about! (And sorry if it's not clear or just wrong, I haven't been a mathematician for thirty years.)

If you think about this for long enough, you should suddenly understand why e to the i pi is minus one. In fact it's just a really obvious thing that has to be true. At that point you've probably got it. 

Comment by johnlawrenceaspden on On the unpopularity of cryonics: life sucks, but at least then you die · 2021-05-19T09:51:41.658Z · LW · GW

My own aged parents have put a very lot of effort into not getting killed by COVID this year, but they're resistant to the idea of cryonics to the point where I've stopped badgering them about it. They actually believe me that it might work, they just don't want to live forever. 

The best argument I can get out of them is that the idea of living forever 'seems a bit American'. 

Comment by johnlawrenceaspden on On the unpopularity of cryonics: life sucks, but at least then you die · 2021-05-19T09:50:26.204Z · LW · GW

So, to summarize, people don't want to live forever because life sucks so why would you want any more of it?

And yet, people seem to put a lot of effort into other life-extension technologies, like diet and exercise and medicine and health-and-safety. 

It seems that people can and do go to great effort to live an extra year or two. It's years in the distant future that they don't want. 

Comment by johnlawrenceaspden on Covid 1/21: Turning the Corner · 2021-01-23T20:28:45.262Z · LW · GW

Am British, confirm.

Comment by johnlawrenceaspden on Coronavirus Transmission · 2020-10-29T11:31:05.309Z · LW · GW

What's Less Wrong's latest thinking on coronavirus transmission methods?

Is this excellent article roughly right?:

https://english.elpais.com/society/2020-10-28/a-room-a-bar-and-a-class-how-the-coronavirus-is-spread-through-the-air.html

How worried should we be about fomite/droplet transmission in comparison?

Comment by johnlawrenceaspden on How strong is the evidence for hydroxychloroquine? · 2020-04-12T10:31:07.060Z · LW · GW

Having had a look, it does seem to me that the malarial areas of the world are much less affected than malaria-free Europe and America, not sure what to read into that, how accurate their figures are, when the first cases were, how slowly we expect coronaviruses to spread in hot places, etc

A shame, since either not-spreading-there or going-like-wildfire would have given a pretty clear answer to the chloroquine question.

At the moment I'm guessing it's weak evidence in favour of effectiveness.

Comment by johnlawrenceaspden on How strong is the evidence for hydroxychloroquine? · 2020-04-12T10:23:01.600Z · LW · GW

It occurs to me that chloroquine is still taken widely in malarial regions as a prophylaxis, even though malaria has developed resistance to it.

So if it worked to deter COVID19, we should be seeing very few cases in, say, Nigeria, where it's a popular over-the-counter treatment even though it's no longer recommended as first-line treatment, and in, say, the Dominican Republic, where malaria isn't yet resistant and it's still the best treatment.

Comment by johnlawrenceaspden on March Coronavirus Open Thread · 2020-04-07T10:23:14.444Z · LW · GW

That's the right stuff I think (chloroquine phosphate, very bitter tasting), would you say that reliablerxpharmacy is a good and trustworthy source?

(not for chloroquine, for meds generally without a prescription)

Comment by johnlawrenceaspden on Popular religions suggest extrapolated volition is non-existence and wireheading · 2018-02-17T19:54:32.393Z · LW · GW

I'm not sure if this is insightful enough to share here, but I'll try anyway.

It sure is. Nice to see someone post something thought-provoking.

Comment by johnlawrenceaspden on Popular religions suggest extrapolated volition is non-existence and wireheading · 2018-02-17T19:48:27.318Z · LW · GW

I think my personal extrapolated volition is wireheading, and I'm definitely in the "Ooh science, what fun" camp.

But maybe I'm not very good at extrapolating, and an AI could come up with something better. It would, for instance, be great to be in a permanent state of bliss whilst actually acting in the world. Or in some private sandbox world occupied by myself and a few hundred friends.

I can't see how those possibilities would feel any different to me from a good wireheading though. And maybe the AI is trying to conserve resources.

Comment by johnlawrenceaspden on Fact Posts: How and Why · 2017-04-20T21:20:18.907Z · LW · GW

"Asimov on Chemistry" was a childhood favourite of mine.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-05-20T22:37:11.182Z · LW · GW

Hi FriendlyBuffalo, welcome to Less Wrong!

I've got no problem with the TSH test as a test for TSH. It's really good for that, and I seriously admire its cleverness and accuracy.

In fact it probably is a good test for primary gland failure. I can't see how the gland itself could go seriously wrong without driving TSH into the stratosphere.

What I hate is the idea that TSH normal <=> 'Thyroid Symptoms, improve when treated with thyroid hormones'. I think there are other dysfunctions going on. The very idea of assessing the state of a system that complicated by measuring one variable (or even three) is ridiculous.

I'm pretty much 'clear clinical picture => therapeutic trial, and sod the blood tests' at the moment, as I think Gordon Skinner was. Of course the problem with that is you end up endorsing leeches and aromatherapy that way. I do have a lot of sympathy for basal metabolic rate, and for waking temperature as a proxy for that.

I think we both agree that some CFS/FMS is just thyroid dysfunction, and will improve with various combinations of thyroid hormones.

The only remaining question for me now is 'Is all of CFS/FMS thyroid related, or just a significant portion of it'?

Lowe reckoned that it was 1/4 primary that had been missed, 1/2 central that there's no test for, and 1/4 the mysterious resistance that he had to overwhelm with high doses of TSH. I see no reason currently to doubt his word, and I'm pretty sure that his work has saved my life (I wouldn't have put up with CFS for much longer. It was awful, and there's no way I'd have found out it was thyroid without Lowe.) So I want to dig into his ideas until I can convince myself that they're either true or false.

If they're false that's really strange. There are now two different diseases, which came into being in the 1970s, which look exactly the same as hypothyroidism, only one of them is, and one of them isn't. I have real trouble with that on Occam's razor grounds.

And that's assuming FMS/CFS/MDD are the same thing. If not then there are three new diseases and some misdiagnosed/mistreated thyroid stuff all pretending to be each other.

I'm really really busy at the moment. I'm so sorry. I've been looking for someone who knows more about this than me for months, and now you show up willing to talk and I've got urgent other things to do. But let us resume discussion at a later date. I've written quite a lot about it here as the idea developed, feel free to debunk it all in absentia mea. I'll come back to all this soon, I'm absolutely sure. I'm obsessed.

I've printed off that paper, it looks really interesting. I'm going to try very very hard not to read it instead of doing the thing I'm supposed to be doing. Thank you very much, and hope to resume discussion soon.

Comment by johnlawrenceaspden on A Medical Mystery: Thyroid Hormones, Chronic Fatigue and Fibromyalgia · 2016-05-20T22:13:01.234Z · LW · GW

That's what I was expecting, but 2.5 isn't suppressed, it's actually quite high compared to the average for healthy people, (or at least normal, depending on what you think normal is). And roughly the same as it was at the start of all this. And both the free hormones look low. You'd think adding a fair bit of thyroid to a healthy system would have bumped up the free hormones and maybe lowered TSH to somewhere like the hyperthyroid range.

What's really weird is that I've tripled the dose of NDT since the last time I had blood drawn, and my TSH has gone up slightly in response. I thought I'd be seriously suppressing my own system by now.

It's possible that I've just developed a primary gland failure, but that's weird because there was no sign of it when I first showed severe symptoms.

Comment by johnlawrenceaspden on A Medical Mystery: Thyroid Hormones, Chronic Fatigue and Fibromyalgia · 2016-05-19T21:47:35.427Z · LW · GW

At the fourth attempt, my doctor managed to get the local lab to test TSH,T3 and T4 simultaneously. He had to ring them up and ask them in person, apparently. It turns out that I've currently got TSH~2.5, and FT4,FT3 low-in-range. Given that that looks like central hypothyroidism, and that's under the influence of 1 grain/day of desiccated thyroid, we've decided we that we have no clue, and I'm carrying on messing around with random thyroid drugs aiming for relief of symptoms (which are all gone, but I keep having to up the dose to keep it so).

Basically Christ knows. If I'm not medically unique, there's something very funny going on.

Comment by johnlawrenceaspden on Welcome to Less Wrong! (8th thread, July 2015) · 2016-05-09T13:22:48.238Z · LW · GW

Welcome Alia! You sure sound like one of us. Hope you like it here.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-05-08T23:23:29.705Z · LW · GW

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?

Comment by johnlawrenceaspden on Talking Snakes: A Cautionary Tale · 2016-05-06T11:33:32.403Z · LW · GW

Took me about 30 seconds, but I'm only an ex-mathematician and I'm not as clever as g!

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-23T23:59:39.094Z · LW · GW

Hi Nancy, thanks! I've already seen that, it's in the evidence section of:

http://lesswrong.com/r/discussion/lw/nef/the_thyroid_madness_core_argument_evidence/

Even more disconfirmy is: http://www.sciencedirect.com/science/article/pii/S0024320515301223

Where some Turkish fibromyalgia patients are actually hotter than they should be, to the point where the authors suggest it as a diagnostic criterion!

There's no doubt they're evidence against. I would have predicted the opposite. When I first saw these two papers (within half an hour) I gave up on the idea. I even told my GP I'd managed to refute it.

But after a couple of days of not believing it, I was just terribly confused, and I realised that they leave me wiggle room.

Basal metabolic rate has to be strongly related to surface temperature (all other things being constant), but there's no reason it should be related to core temperature.

And the thyroid hormones control the basal (i.e. sleeping) metabolic rate, not the active (field) rate.

So I can ignore the Turks (hot during the day), and the main thrust of the Hamilos paper, even though I feel really weaselly doing it.

But, the Hamilos group explicitly considered surface temperature, and they say that they measured basal metabolic rate and it was normal, but they don't give any details, and I can't figure out what they did with either.

If they were careless with the metabolic rate (say, measured it after a rest during the day), it's meaningless as a hypothyroid test. In fact during the day the metabolic rate might actually be higher, if metabolism in hypothyroidism is inefficient because the mitochondria aren't working properly.

And their core graphs do look a bit funny for CFS (but not for depression, which looks normal, sigh..)

On the other hand, Lowe checked for basal metabolic rate and temperature in Fibromyalgia, and found them both way low. I doubt he'd actually have gone to the trouble of trying to break his own idea formally and then faked his data, but it's possible.

And on the third hand, the whole reason for the Hamilos paper is that their CFS patients have been complaining about both low and high temperatures. Why are they doing that? I don't think the 'occult hypothyroidism' idea is well known in CFS circles. One hypothyroid symptom was the rather paradoxical 'intolerance to heat/intolerance to cold'.

I'm just hopelessly confused.

These papers alone, strong evidence against, I think, but not quite refutation.

All the other evidence I've ever seen, strongly in favour.

Skinner's open trial pretty much alone has convinced me that just thyroxine should work, which I didn't believe earlier because it's far too obvious to have been missed. And he also treated depression with it. He considered the possibility of placebo effect, and called for formal trial as one should, but thought it unlikely because the improvements were huge, some of them not subjective, and they were very lasting. And he was a medical researcher, so he knew about fooling himself. And his results are just far too good to be a mistake. He has to be 'right or lying'.

And actually, it seems medical statisticians don't believe in 'the placebo effect'. It's mostly regression to the mean and people trying not to disappoint doctors by saying that things don't work. (That's a bad bias if ever I saw one!)

But people who've been ill for years don't suddenly make full recoveries because you've given them something that should make them more ill, especially when they've all tried loads of freaky stuff before.

The Pollock thing is inexplicable unless their 100mg fixed thyroxine dose helped at least some of their patients. And whatever I think of their selection criteria, they did control properly, and neither of their groups could tell the placebo pills from the thyroxine explicitly, even though the controls were clearly made a bit ill by thyroxine.

In short, I don't actually believe the (widespread occult hypothyroidism) idea. But I do think it's plausible, and I think there's something funny going on with thyroids and all these 'new diseases' and I think I've made a good enough argument that it should be properly trialed.

So I'm now risking talking about it on the reddit CFS group. It seems to be news to them. I'm a bit worried they're all going to do what I did, but they are adults, and it's not very dangerous. I gave them Billewicz statistical test, which is designed to tell 'things that look like hypothyroidism' from 'actual hypothyroidism' by looking at the subtle symptoms like ankle reflexes, and slow movements, and hoarseness and puffy eyes.

So far two people score 'definitely hypothyroid', one 'definitely not', and one hasn't done the test but say's he's got a really good doctor treating his hypothyroidism who's titrating various mixes of thyroid hormones to get rid of all his symptoms but even when they're all gone he's still got disabling fatigue.

But that's even more nuts!

Some CFS is 'occult hypothyroidism' and some is 'something else, definitely not hypothyroidism' is completely crackpot. Not just ordinary crackpot. Occams' Razor! Two different causes for the same thing!

I think we need to take a proper look at all this.

As for the stupidity, whatever I was suffering from (that really does appear to have been occult hypothyroidism by all measures, and that's been apparently completely fixed for months by Floradix and desiccated thyroid) made me as thick as shit. I was so stupid, I couldn't even read. At one point I couldn't count to six. But I still got a couple of hours of lucidity every day, usually in the late evening.

Thanks ever so for you interest, and do send me any more things you dig up. I'm as blind as anyone else, and perfectly capable of ignoring evidence against, even though I'm trying really hard to allow for that!

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-23T18:06:01.624Z · LW · GW

No, it just means we put very little weight on individual studies. We don’t pay much attention to results that haven’t been replicated a few times, and rely heavily on summaries like meta-analyses.

So, for instance, Skinner, who may or may not have demonstrated and published something really important and blindingly obvious in hindsight, gets ignored and then eventually pretty much struck off for it, even though his results could have been put to formal trial for about 50p.

Is the only way we learn anything new if seven different people do the necessary research at their own expense and get their lives destroyed as a consequence?

And nothing done outside the system is worth anything at all?

And the opinions of patients and doctors are 'placebo effect?'.

And the patients' obvious symptoms are 'psychosomatic/somatoform/hypochondriac/malingering'? All the same bloody word, changed every decade or so when people realise what they mean.

And someone invents a wonderful new measurement technique that bears on a hard problem, and it's used to make things worse?

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-23T18:02:37.591Z · LW · GW

No, it just means we put very little weight on individual studies. We don’t pay much attention to results that haven’t been replicated a few times, and rely heavily on summaries like meta-analyses.

So, for instance, Skinner, who may or may not have demonstrated and published something really important and blindingly obvious in hindsight, gets ignored and then eventually pretty much struck off for it, even though his results could have been put to formal trial for about 50p.

Is the only way you learn anything new if seven different people do the necessary research at their own expense and get their lives destroyed as a consequence?

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-23T17:00:48.574Z · LW · GW

Not knowing anything about the subject, I would expect to observe a low basal metabolic rate in CFS regardless of its ultimate cause or causes.

Ooh, why? I thought that was thyroid and starvation?

I mean, low once you adjust for all the known predictive factors, e.g. age, sex, height, weight and exercise. Obviously people who have trouble standing up are going to show low BMR in absolute terms. But I mean 'even after adjusting for sedentary lifestyle'.

Surely the 'stress' theory predicts high BMR?

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-23T16:46:52.053Z · LW · GW

The alt med people have a lot of funding. It’s a multi-billion-dollar industry.

OK, but none of that funding is going in favour of the likes of John Lowe or Gordon Skinner or Barry Durrant-Peatfield or Sarah Myhill, in fact those people are losing/risking their licences and livelihoods in order to try to help people. They may or may not be right about their methods, but they're not doing it for the money!

Ken Blanchard appears to have built an endocrinology practice out of treating hypothyroidism 'functionally', but I'm sure he could have done just as well doing it 'conventionally', and been risking far less legal trouble.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-23T16:42:24.824Z · LW · GW

Okay, but you said it was evidence in favor of your own hypothesis. That’s what my question was about.

I must be confused here. Sorry, I'm not deliberately evading your (good!) question.

If none of the patients had had any sort of thyroid problem, I'd have expected it to be equally bad for everyone. That would be strong evidence against 'it's widespread and treatable with thyroxine', and very weak evidence against 'CFS is thyroidy'.

A test is allowed to produce weak evidence one way and strong evidence the other. Imagine rolling a dice. If it comes out 5, you've not learned much. If it comes out 7, that's a big surprise, and enough to smash the 'six-sided' theory into the very long grass.

If a fair number of the normal-TSH patient group had nevertheless had a thyroid problem amenable to thyroxine 100mg/day, then I'd have expected that to make a difference between healthy controls and patients. Which appears to be what happened. I think that's actually fairly strong evidence in favour of 'common and treatable with thyroxine'. Nowhere near proof, but it strengthens Skinner's paper, which is already strong evidence, rather than weakening it.

I'm actually really surprised by that. That thyroxine made any difference at all.

I believed it was thyroidy just on the argument in 'A medical mystery'. (Looks like hypothyroidism, existed in Victorian times, didn't exist 1900-1970 when hypothyroidism was diagnosed by symptoms and treated with desiccated thyroid, which has too much T3 in it, validity of TSH test never checked)

I've been saying for a while that it must be to do with T4/T3 balance, because I couldn''t believe that if it was amenable to thyroxine that wouldn't already be known. Because I literally couldn't believe that medical science could have been that careless and stupid.

But now I'm looking at the only two papers I've ever been able to find on the subject, and thinking, 'they both imply that thyroxine works'. It might not be optimal, but it seems to do something!

And sure, it's nowhere near proof, and I wouldn't want public health policy changed on this kind of evidence. But it's worth a good look. And the level of carelessness implied is just staggering.

If they'd just made a terrible mistake and then ignored millions screaming for help for forty years, that would be criminal, but John Lowe and lots of medical doctors had/have been asking, perfectly clearly and sanely, for endocrinology to check its beliefs, for decades. And they've been marginalised, ridiculed, and persecuted for it. "TSH tests normal, therefore it can't be a thyroid issue." Over and over and over again. No evidence whatsoever. Even if CFS turns out to be caused by magic space pixies who deliberately confuse all the experiments, medical science has my utter contempt. Six months ago I would have said: "There's no point to alternative medicine, if they had anything that worked it would just be real medicine.". In fact my friends (and the chiropractor I used to go and see even though I believed her treatments didn't really help and I was allowing myself to buy a placebo) tell me I used to say that quite a lot. Because I trusted something extravagantly publicly funded, that called itself a science, to use the scientific method. After taking a (fairly brief) look at this one problem, I'm now thinking "How many lives have these morons fucked up through their arrogance and carelessness?". "How much of the random crap in Holland and Barrett actually works, and how much public money is being shoved down the drain buying chemical poisons for the ill on dodgy evidence produced by drugs companies when they could be fixed with cheap treatments that have been known for years?"
Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-22T15:27:12.922Z · LW · GW

Oh God, where will this end? Is it really only physics and chemistry that aren't sloppy cargo-cults, or are they broken too?

A lot of this, I think is to do with taking tenure away from young academics. Once upon a time once you'd proved basic competence and cleverness, you could spend your whole career being careful about stuff. These days you've just got to turn out crap as fast as possible. And you spend most of your time applying for grants.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-22T15:13:03.013Z · LW · GW

Tsk, summoning the mind-killer in broad daylight. This is supposed to be a family-friendly discussion of taking mad drugs off of the internet for made-up diseases in futile defiance of medical advice. Let us not side-track onto the emotive issue of banana curvature, which is very difficult and sensitive for the English people (sniff).

Downvote me back, will you? Tit-for-tat is the whole of the law.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-21T15:45:42.233Z · LW · GW

Well quite. In America I think there have been episodes of 'hamburger thyrotoxicosis', so putting thyroids in food is now illegal, which is good. I'm not sure what the European situation is.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-21T15:23:32.652Z · LW · GW

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.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-20T22:58:07.273Z · LW · GW

P.S. Note the awe-inspiring lack of smugness with which I present:

IMPAIRED ACTION OF THYROID HORMONE ASSOCIATED WITH SMOKING IN WOMEN WITH HYPOTHYROIDISM

BEAT MÜLLER , M.D., HENRYK ZULEWSKI , M.D., PETER HUBER , P H .D., JOHN G. RATCLIFFE , M.D., AND JEAN -JACQUES STAUB , M.D.

I bloody said it would turn out to be the reason smoking's bad for you, didn't I? And at the same time it's evidence that acquired hormone resistance exists, and this one fingers an environmental cause.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-20T22:33:44.341Z · LW · GW

Isn't it still "its day"?

Opinions are divided. There's me and some dead guys, and everyone else. Everyone else thinks it's a solved problem.

By the way, the people who you insist on calling "fat, tired, and with dry skin" are in subset three. They exhibit clinical symptoms of hypothyroidism.

They absolutely do! Back in the day, they would have been referred to endocrinologists on suspicion of hypothyroidism, who would have (if they were very sophisticated and modern endocrinologists) used Billewicz' test to sort them into definite, definitely not, and 'therapeutic trial' groups. His test didn't rate these three symptoms, or lethargy or stupidity, because most everyone he saw had them, so he would look at all their other symptoms to make the diagnosis, looking for things like slow reflexes that are characteristic of hypothyroidism, and weight them to get a score. It really is a very careful piece of work, that test.

He would treat the 'definites' without further ado, send the 'definitely nots' off to people who were into diabetes etc, and be careful with the rest. Including all sorts of unreliable lab tests and therapeutic trials.

Luckily the therapeutic trials are not difficult to do, because with desiccated thyroid/T3 you seem to get either get a fairly rapid improvement, or you get hyper symptoms. (you might get both of course, in which case dose probably too high)

Other popular ways of trying to work it out involved cholesterol and basal metabolic rate.

Broda Barnes thought waking armpit temperature beat all this and just handed it out to anyone who woke up cold.

And the fact that it has been sprayed around at random for a hundred years without anyone having a word to say against it implies that it's pretty damned safe. If you give yourself a massive overdose, then sure, you can probably give yourself a heart attack, but you'd need to be way way more criminally careless than I can imagine any (modern) doctor being.

Osteoporosis and atrial fibrillation (both ghastly things) are associated with low TSH, so it's doubtless not a good idea to induce hyperthyroidism in people. And I think we should be careful not do that.

Barnes might have been deluded. I certainly started off thinking that he was, but one thing he was into was records and statistics. He thought his patients healthier than the general population. Including low rates of heart trouble. Which is just bizarre if what he was seeing was today's CFS etc population, who seem to be really ill and then go on to be even more ill. Unless his treatments actually helped.

Hell, let's do all four! If there's a subset of fat tired stupid lethargic CFS patients with dry skin and high Billewicz scores, low basal metabolic rates, high cholesterol, and low waking temperatures all at the same time, then let's run the Scottish trial on them and see what happens. That should be enough to break the TSH test, at which point, I imagine there will be an absolute explosion of research.

I couldn't agree more that it's really really important to understand mechanism. I'm into 'explanations' and 'causes'. I think you are too. I get the impression that they're a bit out of fashion in medicine.

Well, it's pretty clear that it will help some people

Ooh, is it me and you and some dead guys now? Welcome! Sorry some of us aren't that talkative. Damnit, that means I need another opponent. Devil's advocate isn't good enough. It needs to be someone who hates the idea.

Dies at noon.

Oh dear, poor Charles. The English crown was a bit of a poisoned chalice for the Stuarts wasn't it? Still, he made it to 53 and they did call him the Merry Monarch. Anyone who dies in office of excessive mistress-related-activity hasn't had a totally wasted life.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-19T22:50:55.249Z · LW · GW

I’m talking about conservation of expected evidence.

Sure, this experiment is evidence against 'all fat, tired people with dry hair get better with thryoxine'. No problem there.

Terminology then. When you said “Thyroxine is very strongly disliked by the healthy controls (they could tell it from placebo and hated it),” it suggests they could identify the active treatment.

Yes, it is kind of odd isn't it? One of the pills apparently made them a bit unwell, and yet they couldn't tell which one. I notice that I am confused.

The people in the study had symptoms.

You're right. I think I should have said "This treatment is harmful to most people".

This is normal...

But that's awful! Once, there was a diagnostic method, and a treatment that worked fine, that everyone thought was brilliant. Then they invented a test, which is very clever, and a good test for what it tests, and the result of that is that lots of people are ill and don't get the treatment any more and have to suffer horribly and die early.

If that's normal then there's something badly wrong with normal. A new way of measuring things should help!

we have to decide which ones are worth considering.

Sure, I'm trying to make a case that this one is worth considering.

it might not be possible to design a study ..

I think the Scottish study with stricter entry criteria for the patient group would do. If that failed, I would be quite surprised.

If someone did the same thing with stricter entry criteria and used desiccated thyroid and titrated doses and it failed I would be so surprised that I would give up.

Seriously, if 'start off with low doses and keep raising the dose until you get a response' is inaccessible to testing, then something is broken.

But in fact, just 'low basal metabolic rate in CFS' would be good evidence in favour, I think. We can work out optimal treatments later.

And if it turned out that there wasn't a subset of CFS patients with high Billewicz scores and low basal metabolic rates, I'd give up. No study needed.

I can’t stress this enough: in biology, you can use peer-reviewed evidence to make plausible arguments for arbitrary hypotheses.

At that point, we're all post-modernists aren't we? The truth is socially determined.

science is unreliable but is still better than ancestral wisdom

Science is not unreliable. If I can surprise a physicist or a chemist about something he is sure of, he will be very very interested, and science will quickly rearrange itself around the new fact. It took about five years to completely overturn classical physics and replace it with something we haven't managed to surprise yet, even though everyone knows that the new theories are broken and is actively trying to find things that happen that they don't predict. And classical physics is still damned good in the domains that it used to work in.

There's at least a possibility here that medical science is getting beaten hollow by chiropractors and quack doctors and internet loonies, none of whom have any resources or funding at all.

Even the possibility is enough to make me think that there's something appallingly badly wrong with the methods and structure of medical science.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-19T21:37:06.116Z · LW · GW

Well, 'hypothyroidism' was a very difficult and polymorphic badger in its day. But a thing that is difficult to detect can still be a thing. Consider neutrinos and gravity waves and unicornes, which no man nowadays doubts of.

And as for 'medicalise deviations from the theoretical optimum', most chronic fatigue people are already bothering their poor doctors incessantly, and being given (with the best will in the world) a selection of nasty things that mildly alleviate some of their symptoms. CFS is a horrible thing. As Hitler says in the film Downfall:

"'Chronic Fatigue Syndrome' ? they might as well call Leprosy : 'Chronic Dandruff Syndrome'".

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-19T21:28:59.492Z · LW · GW

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!

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-18T20:11:54.067Z · LW · GW

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.

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-18T20:07:41.122Z · LW · GW

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'

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-18T17:52:16.071Z · LW · GW

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?

Comment by johnlawrenceaspden on The Thyroid Madness: Two Apparently Contradictory Studies. Proof? · 2016-04-18T17:46:43.674Z · LW · GW

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.