Do you mean the pronouns used to address your character are automatically edited to be what you want?
It would be interesting if people could put up lists of the pronouns they prefer, and that would give them a tool for roughly judging how much trouble people are willing to go to to appear to be on their side.
Are there any games which encourage a you/thou distinction?
No, but there's American English. I've been trying to introduce you and y'all in Cambridge, it's pretty cool.
You are falling prey to the typical mind fallacy. The meaning you ascribe to your words in not how a stranger would read them.
You asked about thyroid hormone resistance. The "actual endocrinologist" knows what that is -- it is a genetic condition. So he assumes you are talking about the genetic problem (RTH) but you are terribly confused because you somehow think that genetic conditions can be acquired after birth. At this point he probably stopped reading because why bother.
Oh, well spotted! Can anyone suggest a better crank e-mail? This is actually the only one I've sent since I found Skinner's paper, which is the thing that made me go from 'dark suspicion' to 'bloody hell, this is probably true'.
"If we hand this out to fat, tired people with dry skin, does it work?". And the answer to that is: "On average they can't tell the difference between that and placebo.
I'm confused. Aren't these clinical symptoms of hypothyroidism?
Besides, "works / doesn't work" seems like a too crude approach. There is a large middle zone of "works for some people some of the time" and there you have roll up your sleeves and get into the messy details which might still not give you enough information to be able to predict for which people at which time your treatment will work (or not).
The "theoretically correct" approach would be, I think, to do a deep dive into biochemistry and figure out all the links in the mechanism connecting the T levels in the blood with the activity of the mitochondria. Once you do that, figuring out which link is broken in a particular patient subset shouldn't be too hard. But the initial research, mapping out the chain of effects, looks daunting.
I'm confused. Aren't these clinical symptoms of hypothyroidism?
Ah. They are clinical symptoms of hypothyroidism. But they are also symptoms of all sorts of other things. In fact they are symptoms that occur in people who have nothing wrong with them at all.
To diagnose it by clinical symptoms you have to be much more careful than that! See e.g. Billewicz paper.
More specific symptoms were apparently things like ankle tendon reflex, and cholesterol levels, but you need to be really careful. The disease was known as 'the great imitator'. It's easy to confuse with other things, and diagnosing it was really difficult and a job for trained professionals.
I got the impression that if they had strong suspicions, they'd just try thyroid hormones and see if they worked.
Oh the effect is definitely small. They do however note observable differences in the hormones down to a thousandth the dose that caused histological changes, albeit without being able to see secondary effects on quantifiable health outcomes. No idea at all if that's significant but figured I'd contribute it to the discussion of subtle thyroid dysfunction.
Well, I don't want to sound like an endocrinologist, but there aren't many chemicals which don't have some sort of effect on thyroid hormones, and if this one screwed up the system in a way measurable by hormone blood tests, it would just cause ordinary hypothyroidism, and that would get treated.
As far as I can see, the evidence for it causing any sort of subtle dysfunction is non-existent. All I've seen is the one study, but it sounds from that as though it would be safe to ingest in small doses.
Oh, and a postscript.
Gordon Skinner wrote a book: Diagnosis and Management of Hypothyroidism
It's digressive, irreverent, and gloriously politically incorrect. I love it, but I recognise a certain British sense of self-deprecating humour which will not go down terribly well with everyone.
In my reading of it, he is full of self-doubt, and finds the behaviour of his own profession ridiculous and is hiding behind his jokes and raw language.
He describes many years of treating hypothyoidism by its symptoms, pretty much ignoring lab tests. As he describes it, it is quite hard to get wrong, and the major danger is missing other diseases, which also don't show up on the standard tests.
He claims to get hundreds of patients every year, and he doesn't report many cases where he got it wrong.
Now, this man is right, or he is completely deluded, or he is lying.
I find it impossible to imagine what his motive for lying might be.
Towards the end of his career and life, apparently, the GMC decided to make an example of him, and ordered him never again to prescribe thyroid hormones without the consent of an endocrinologist.
Can anyone find out why they did this? Did they have any good reason?
He appears to have spent the rest of his life advising various internet thyroid support groups, and campaigning against the TSH test.
Gordon Skinner died in 2013.
Here is what some thyroid internet loonies wrote as his obituary:
http://www.stopthethyroidmadness.com/2013/11/28/gordon-skinner/
What was he, people? Saint or madman? I think he has to have been one or the other.
I got a reply from an actual endocrinologist! I'm not going to use his name because ethics, and because it was kind of him to reply at all, and more than any of his colleagues have done, but am I wrong to detect a certain lack of curiosity? Or do you think they're all too busy beavering away at the problem to bother answering e-mails from cranks?
to: <secret> subject: crank-trap
Dear [First Name],
Is there any reason why people think that thyroid hormone resistance is only congenital and never acquired?
Given the widespread acquired resistance to insulin it seems an obvious thing to look for.
I imagine you get a lot of e-mails. Please don't feel you need to make a lengthy reply. A link to a paper or web page will do!
John.
P.S. I've attached a paper by one GRB Skinner in Birmingham, UK. Assuming he's not just making up his data it's hard to explain his results.
[Attached Skinner paper where he cures 140 people with hypothyroid symptoms but normal blood tests by giving them thyroxine]
reply:
Mr. Aspden, Diseases have names and definitions. It so happens that the term resistance to thyroid hormone (RTH) is applied to a syndrome, inherited in a dominant fashion. It has three forms RTH alpha, RTH beta and nonTR-RTH. What is described in the publication you attached does not have the clinical findings and laboratory tests results of RTH. The authors have not found the cause nor given a name for what they describe.
Regards,
[secret]
A study that saw statistically significant hormone effects
First, 10 mg/kg/day is a LOT (that's mg, not mcg).
Second, while there were morphological changes ("significantly increased thyroid weights and thyroid histopathology") and some changes in the TSH/T3/T4, the study notes that "No toxicologically meaningful differences were observed between the control and AP-treated groups" which means there were no clinical symptoms whatsoever.
I totally concur. 10mg/kg/day is a gram a day. If I took that amount of thyroid hormone, which I believe to be one of the safest drugs ever used, and of huge benefit to a large subset of the population, I would confidently expect to give myself an immediate heart attack. At the very least it would make me spectacularly ill.
No toxicologically meaningful differences were observed between the control and AP-treated groups with respect to survival, clinical observations, body weights, food consumption, water consumption, ophthalmology, hematology, clinical chemistry, estrous cycling, sperm parameters, or bone marrow micronucleus formation.
So it's not buggered them up too badly.
For comparison, if you took the poor wee things' thyroids out, then you'd expect them to display horrible symptoms and die off in droves.
Well, talking about it, admitting doubt, those sorts of things would be a start.
Before this became something routinely done on the NHS, it would need cast-iron proof sufficient to convince NICE, and I approve of that wholeheartedly. But there are a lot of smaller steps between 'suspicion' and 'certainty'.
Can doctors just try to give things like dessicated thyroid to their patients?
They used to hand it out routinely, back in the days when hypothyroidism was diagnosed by symptoms (up to ~1965), and everyone thought it was as good as medicine got. There seems to have been huge pressure to stop doing that, including striking people off, and I wonder what evidence was used to support those processes. If there is any, that's what I'm looking for.
Now, I think you might be in serious trouble for not following the guidelines. The guidelines for CFS say: 'don't use thyroxine'. But they don't give a reason or a reference. It's mad.
In America, apparently, doctors are much freer to try things, and some of them do, in full knowledge that endocrinologists disapprove, and it works.
But actually, desiccated thyroid is also available as a 'food supplement', and you don't need a prescription for it in England or America, so chiropractors and osteopaths and homeopaths and naturopaths and mad people on the internet and the like are free to tell people to take it. And they do. And then they write books about it. Just Google!
Well, it's been done and the results, as you are well aware of, are inconclusive.
Actually, I'm not well aware of that. I really haven't found anyone saying 'We tried this on people with hypothyroid symptoms, and it just made them hyperthyroid, as you'd expect." Everyone who's tried it seems to think it works a treat. I'd love to see counter-evidence if you can find any.
The worst anyone has to say is: "It works most of the time, but often we find that there's something adrenal going on as well, and in those people we have to fix both".
The question answered inconclusively was "If we hand this out to fat, tired people with dry skin, does it work?". And the answer to that is: "On average they can't tell the difference between that and placebo.
But they also proved that healthy people can tell the difference on average, and they don't like it. Presumably because it gives them hyperthyroid symptoms, which aren't very nice.
Everyone who's ever tried fixing the clinical diagnosis of hypothyroidism with any kind of thyroid therapy either seems to think it works, or hasn't written about it on the internet or in the medical literature.
That's a big claim. I'm making it in bold on Less Wrong. I expect someone to turn up some evidence against it. I would love to see that evidence.
I find this bewildering. I thought that the problem would be complicated and difficult.
And at the moment I'm just staring in disbelief. What the hell is going on?
Oh, I'd like to say that none of that makes hypothyroidism the sole cause of CFS. There appears to be raised heart rate in CFS, which seems strange if it's primarily a thyroid underregulation problem.
But 'diagnose hypothyroidism by symptoms, ignore TSH, treat with any sodding thyroid hormone you like', seems to be straightforwardly the right thing to do, and uncontroversial amongst people who've tried it. All the debate is about what the best combination of T4/T3 is. But they all agree that they all work fairly well.
And at least some 'hypothyroid symptoms, normal TSH' people are going to end up diagnosed CFS, FMS, IBS, MDD, etc, etc, etc....
some of them think this is worth a look, and some of them know eminent medical researchers. There's just a wall of silence. I can't explain it.
What would "taking a look" entail? Taking it seriously means a large study which means applying for grants, going through ethics boards, devoting a lot of time and energy to it, etc. That's a rather big project and, presumably, serious people would require good reasons to commit to such a project.
Other than a full-blown study, what else? Can doctors just try to give things like dessicated thyroid to their patients? Well, it's been done and the results, which you are well aware of, are inconclusive. Besides, I don't think the NHS would look kindly on such "experiments" which I'm pretty sure go outside of the accepted guidelines.
Basically I think there is a large barrier to entry and no one is motivated enough to bring a wrecking ball.
Well, talking about it, admitting doubt, those sorts of things would be a start.
Before this became something routinely done on the NHS, it would need cast-iron proof sufficient to convince NICE, and I approve of that wholeheartedly. But there are a lot of smaller steps between 'suspicion' and 'certainty'.
Can doctors just try to give things like dessicated thyroid to their patients?
They used to hand it out routinely, back in the days when hypothyroidism was diagnosed by symptoms (up to ~1965), and everyone thought it was as good as medicine got. There seems to have been huge pressure to stop doing that, including striking people off, and I wonder what evidence was used to support those processes. If there is any, that's what I'm looking for.
Now, I think you might be in serious trouble for not following the guidelines. The guidelines for CFS say: 'don't use thyroxine'. But they don't give a reason or a reference. It's mad.
In America, apparently, doctors are much freer to try things, and some of them do, in full knowledge that endocrinologists disapprove, and it works.
But actually, desiccated thyroid is also available as a 'food supplement', and you don't need a prescription for it in England or America, so chiropractors and osteopaths and homeopaths and naturopaths and mad people on the internet and the like are free to tell people to take it. And they do. And then they write books about it. Just Google!
Well, it's been done and the results, as you are well aware of, are inconclusive.
Actually, I'm not well aware of that. I really haven't found anyone saying 'We tried this on people with hypothyroid symptoms, and it just made them hyperthyroid, as you'd expect." Everyone who's tried it seems to think it works a treat. I'd love to see counter-evidence if you can find any.
The worst anyone has to say is: "It works most of the time, but often we find that there's something adrenal going on as well, and in those people we have to fix both".
The question answered inconclusively was "If we hand this out to fat, tired people with dry skin, does it work?". And the answer to that is: "On average they can't tell the difference between that and placebo.
But they also proved that healthy people can tell the difference on average, and they don't like it. Presumably because it gives them hyperthyroid symptoms, which aren't very nice.
Everyone who's ever tried fixing the clinical diagnosis of hypothyroidism with any kind of thyroid therapy either seems to think it works, or hasn't written about it on the internet or in the medical literature.
That's a big claim. I'm making it in bold on Less Wrong. I expect someone to turn up some evidence against it. I would love to see that evidence.
I find this bewildering. I thought that the problem would be complicated and difficult.
And at the moment I'm just staring in disbelief. What the hell is going on?
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Games typically will avoid pronouns and just use the character's name. It's not hard because most of the dialogue in games is addressed to the player and is not two NPCs talking about the player.
In English the only reason to use thou would be some fake medievalism along the lines of Ye Olde Electronics Shoppe. But I wonder how things work in e.g. French where tu/vous distinction is alive and well.
Cabinet Minister: On se tutoie?
Mitterand: Si vous voulez.
Actually it's dying out in French (or possibly going back to being a singular/plural distinction rather than a familiar form), I sound gloriously stuffy because I'm not very good at the tu forms and tend to call people vous even once I've been properly introduced. My French teacher said "You will never know anyone French well enough to call them tu, so there's not much point in learning that, except for the exam". That was probably true in the 1950s.
In Greek and German it's even worse, the second person singular and plural are both familiar, for friends and family only. With strangers you have to say things like: "Would the gentleman care for a glass of beer", and sound like some sort of creepy servant.