I'm not sure if this is insightful enough to share here, but I'll try anyway.
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.
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.
"Asimov on Chemistry" was a childhood favourite of mine.
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.
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.
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.
Welcome Alia! You sure sound like one of us. Hope you like it here.
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?
Took me about 30 seconds, but I'm only an ex-mathematician and I'm not as clever as g!
Hi Nancy, thanks! I've already seen that, it's in the evidence section of:
Even more disconfirmy is:
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!