I've made a couple of recent posts about hypothyroidism:


It appears that many of those who read them were unable to extract the core argument, and few people seem to have found them interesting.

They seem extremely important to me. Somewhere between a possible palliative for some cases of Chronic Fatigue Syndrome, and a panacea for most of the remaining unexplained diseases of the world.

So here I've made the core argument as plain as I can. But obviously it misses out many details. Please read the original posts to see what I'm really saying. They were written as I thought, and the idea has crystallised somewhat in the process of arguing about it with friends and contributors to Less Wrong. In particular I am indebted to the late Broda Barnes for the connection with diabetes, which I found in his book 'Hypothyroidism: The Unsuspected Illness', and which makes the whole thing look rather more plausible.


(1.1) Hypothyroidism is a disease with very variable symptoms, which can present in many different ways.

It is an endocrine hormone disease, which causes the metabolism to run slow. A sort of general systems failure. Which parts fail first seems random.

It is extraordinarily difficult to diagnose by clinical symptoms.

(1.2) Chronic Fatigue Syndrome and Fibromyalgia look very like possible presentations of Hypothyroidism

(1.3) The most commonly used blood test (TSH) for Hypothyroidism is negative in CFS/FMS



(2.1) CFS/FMS/Hypothyroidism are extremely similar diseases which are nevertheless differently caused.


(2.2) The blood test is failing to detect many cases of Hypothyroidism.

It seems that one is either forced to accept (2.1), or to believe that blood hormone levels can be normal in the presence of Hypothyroidism.

There is precedent for this:

Diabetes, another endocrine disorder (this time the hormone is insulin), comes in two forms:

type I : the hormone producing gland is damaged, the blood hormone levels go wrong.         (Classical Diabetes)

type II: the blood hormone levels are normal, but for some reason the hormone does not act. (Insulin Resistance)

I therefore hypothesize:

(3) That there is at least one mechanism interfering with the action of the thyroid hormones on the cells.


(4) The same, or similar mechanisms can interfere with the actions of other hormones.

A priori, I'd give these hypotheses a starting chance of 1%. They do not seem unreasonable. In fact they are obvious.

The strongest evidence against them is that they are so very obvious, and yet not believed by those whose job it is to decide.



CURRENT STATUS  (Estimated probability)

(1.1) Uncontroversial, believed by everyone involved (~100%)

(1.2) Similarly uncontroversial (~100%)

(1.3) By definition. With abnormal TSH, you'd have hypothyroidism (~100%)

(2.1) Universal belief of conventional medicine and medical science, some alternative medicine disagrees (~90%)

(2.2) The idea that the TSH test is inaccurate is widely believed in alternative medicine, and by thyroid patient groups, but largely rejected by conventional medicine (~10%)

(3) There is some evidence from alternative medicine that this might be true (~10%)

(4) My own idea. A wild stab in the dark. But if it happens twice, you bet it happens thrice [1] (~0.000001%)

Some Details

(1.1) Clinical diagnosis of Hypothyroidism is very out of fashion, considered hopelessly unreliable, doctors are actually trained to ignore the symptoms. There is a famous medical sin of 'Overdiagnosing Hypothyroidism', and doctors who fall into sin are regularly struck off.

(1.2) I don't think you'll find anyone who knows about both diseases to dispute this.

(1.3) True by definition. CFS/FMS symptoms plus abnormal TSH would be Hypothyroidism proper, almost no-one would disagree.

(2.1) This is the belief of conventional medicine. But the cause of CFS/FMS is unknown.

Generally the symptoms are blamed on 'stress', but 'stress' seems to be 'that which causes disease'. This 'explanation' seems to be doing little explanatory work. In fact it looks like magical thinking to me.

Medical Scientists know much more about all this than I do, and they believe it.

On the other hand, scientific ideas without verified causal chains often turn out to be wrong.

(2.2) (The important bit: If the TSH test is not solid, there are a number of interesting consequences.)

I've been looking for a few months through the endocrinological literature for evidence that the sensitivity of the TSH test was properly checked before its introduction or since, and I can't find any. It seems to have been an unjustified assumption. At the very least, my medical literature search skillz are not up to it. I appeal for help to those with better skillz.

It is beyond doubt that atrophy or removal of the thyroid gland causes the TSH value to go extremely high, and such cases are uncontroversial.

The actual interpretation of the TSH test is curiously wooly.

It has proved very difficult to pin down the 'normal range' for TSH, and they have been arguing about it for nearly forty years, over which the 'normal range' has been repeatedly narrowed

The AACB report of 2012 concluded that the normal range was so narrow that huge numbers of people with no symptoms would be outside it, and this range is not widely accepted for obvious reasons

There are many other possible blood hormone tests for hypothyroidism. All are considered to be less accurate or less sensitive than the TSH test. It does seem to be the best available blood test. It does not correlate particularly well with clinical symptoms.

(3) Broda Barnes, a conventional endocrinologist working before the introduction of reliable blood tests, was convinced that the most accurate test was the peripheral basal body temperature on waking.

He considered measuring the basal metabolic rate, and rejected it for good reasons. He considered that desiccated thyroid was a good treatment for the disease, and thought the disease very common. He estimated its prevalence at 40% in the American population. His work is nowadays considered obsolete, and ignored. But he seems to have been a careful, thoughtful scientist, and the best arguments against his conclusions are placebo-effect and confirmation bias. He treated thousands of patients, his treatments were not controversial at the time, and he reported great success. He wrote a popular book 'Hypothyroidism: The Unsuspected Illness', and his conclusions have fathered a large and popular alternative medicine tradition.

John Lowe, a chiropractor who claimed that fibromyalgia could be cured with desiccated thyroid, found that many (25%) of his patients did not respond to the treatment. He hypothesised peripheral resistance, thought it genetic, and used very high doses of the thyroid hormone T3 on many of his patients, which should have killed them. I have read many of his writings, they seem thoughtful and sane. I am not aware of any case in which John Lowe is thought to have done harm. There must be some, even if he was right. But if he was wrong he should have killed many of his patients, including himself. He was either a liar, or a serial murderer, or he was right. He was likely seeing an extremely biased sample of patients, those who could not be helped by conventional approaches.

(4) I just made it up by analogy.

There is the curious concept of 'adrenal fatigue', widespread in alternative medicine but dismissed as fantasy outside it, where the adrenal glands (more endocrine things) are supposed to be 'tired out' by 'excessive stress'. That could conceivably be explained by peripheral resistance to adrenal hormones.


If (3) is true but (4) is not:

There are a number of mysterious 'somatoform' disorders, collectively known as the central sensitivity syndromes, with many symptoms in common, which could be explained as type 2 hypothyroidism. Obvious cases are Chronic Fatigue Syndrome, Fibromyalgia Syndrome, Major Depressive Disorder and Irritable Bowel Syndrome, but there are many others. Taken together they would explain Broda Barnes' estimate of 40% of Americans.

If (4) is true:

Then we can probably explain most of the remaining unexplained human diseases as endocrine resistance disorders.




This is the million-dollar question!

My favourite explanation is that in order to overwhelm 'peripheral resistance to thyroid hormones', one needs to give the patient both T4 and T3 in exactly the right proportions and dose.

Supplementation with T4 alone will not increase the levels of T3 in the system, since the conversion is under the body's normal control, and the body defends T3 levels.

But T3 is the 'active hormone'. Without significantly increasing the circulating levels of T3, the resistance cannot be overwhelmed.

On the other hand, any significant overdosing of T3 will massively overstimulate the body, causing the extremely unpleasant symptoms of hyperthyroidism.

This seems to me to be sufficient explanation for why various trials of T4 supplementation on the central sensitivity disorders have all failed. In almost all cases, the patients will either have seen no improvement, or have experienced the symptoms of over-treatment. Only in very few cases will any improvement have occurred, and standard trials are not designed to detect such effects.

It is actually just luck that the T4/T3 proportion in desiccated thyroid is about right for some people.

Alternatively, there may just be some component in desiccated thyroid whose action we don't understand.


I displayed symptoms of mild-to-moderate Chronic Fatigue Syndrome, and my wonderful NHS GP checked everything it could possibly be. All my blood tests normal, TSH=2.51. I was heading for a diagnosis of CFS.

After four months I mysteriously partially recovered after trying the iron/vitamin B supplement Floradix, even though I wasn't anaemic.

I started researching on the basis that things that go away on their own tend to come back on their own.

I noticed that I had recorded, in records kept at the time of the illness, thirty out of a list of forty possible symptoms of Hypothyroidism, drew the obvious conclusions as so many others have, and purchased a supply of desiccated thyroid in case it came back.

It did come back, and after one month, I began to self-treat with desiccated thyroid, very carefully titrating small doses against symptoms, and quickly noted immediate huge improvement in all symptoms. In fact I'd say they were gone.

My basal temperature rose over a few weeks from 36.1 to ~36.6 (average, rise slow over several weeks, noise ~ +-0.3 day to day).

One week, holding the dose steady in anticipation of more blood tests, I overdid it by the truly minute amount of 3mg/day of desiccated thyroid, which caused all of the symptoms of the manic phase of bipolar disorder (whose down phase is indistinguishable from CFS, and whose up phase looks terribly like the onset of hyperthyroidism), The manic symptoms disappeared within twelve hours of ceasing thyroid supplementation, to be replaced by overwhelming tiredness.

I resumed thyroid supplementation at a slightly lower dose, and feel as well as I have done for ten years. It's now been ten weeks and I am becoming reasonably confident that it is having some effect.


Such catastrophic failures of the body's central control system CANNOT be evolutionarily stable unless they are extremely rare or have compensating advantages.

I am thus drawn to the idea of either:

(a) recent environmental change (which seems to be the alternative medicine explanation)

(b) immune defence (which would explain why e.g. CFS often presents as extended version of the normal post-viral fatigue)

If the alternative is being eaten alive, it seems all too plausible that an immune mechanism might be to 'wall off' cells in some way until the emergency is past, even if catastrophic damage is a side effect.


Low Body Temperature

It is a very strong prediction of this theory that low basal metabolic rates, and thus low basal peripheral temperatures will be found in many sufferers of Chronic Fatigue Syndrome and Fibromyalgia.

If this is not true, then the idea is refuted unambiguously.

Thyroid Hormone Supplementation as Palliative

It is a less strong prediction, but still fairly strong, that supplementation of the hormones T4 and T3 in carefully titrated doses and proportions will relieve some of the symptoms of CFS/FMS.

Note that T4 supplementation alone is unlikely to work. And that unless the doses and proportions are carefully adjusted to relieve symptoms, the treatment is likely to either not work, or be worse than the disease!


I've been very reluctant to draw my wilder speculative conclusions in public, since they have the potential to do great harm whether or not the idea is true, but here are some of the less frightening ones that I feel safe stating:

I state them only to encourage people to believe that this problem is worth thinking about.

Endocrinology appears not to be too interested, and my crank emails to endocrinologists have gone unanswered.

One of the reasons that I feel safe stating these four in public is that Broda Barnes thought them obvious and published popular books about them, so they are unlikely to come as a surprise to anyone outside endocrinology:

Dieting/Exercise/Weight Loss

Dieting and Exercise don't work long term as treatments for weight loss. The function of the thyroid system is to adapt metabolism to available resources. Starvation will cause mild transient hypothyroidism as the body attempts to survive the famine it infers. This may be the explanation for Anorexia Nervosa.


Diagnosis of diabetes was once a death sentence. With the discovery of insulin, allowing diabetics to control their blood sugar levels, it became survivable.

However it still has terrible complications, a lot of which look like the complications of hypothyroidism.

If a hormone-resistance mechanism interferes with both insulin and thyroid hormones, the reason for this is obvious. Diabetics with well-controlled blood sugar are dying in their millions from a treatable condition.

Heart Disease

One of the very old tests for hypothyroidism was blood cholesterol. It was thought to be a reliable indicator of hypothyroidism if present, but it was not always present.

A known symptom of hypothyroidism is atherosclerosis and weakness of the heart.

I would imagine that hypothyroidism initially presents as low blood pressure, due to the weakness of the heart. As the arteries clog, the weakened heart is forced to work harder and harder. Blood pressure goes higher and higher, and eventually the heart collapses under the strain.

Blood pressure reducing medications may actually be doing harm. A promising treatment might be to correct the underlying hypothyroidism.


Cigarettes are full of poisons, and smoking is correlated with very many diseases.

It could be that smoking causes amongst its effects peripheral resistance, which causes clinical hypothyroidism, which then causes everything it usually causes. And that would be my bet!

It could be that hypothyroidism causes a very great number of bad things, including depression, which then causes smoking.

Smoking may not actually be that dangerous, and it might be possible to mitigate its bad effects.


[1] Madonna, "Pretender", Like A Virgin, Power Station Studios, New York, New York (1984)

I'm going to stop there. There are quite a lot of similar conclusions to be drawn. Read Barnes.

I also have some novel ones of my own which I am not telling anyone about just yet.

What the hell do I, or any of the quacks who have been screaming about this for forty years, have to say in order that someone with real expertise in this area takes this idea seriously enough to have a go at refuting it?



EDIT: This keeps confusing people (including me): Low Basal Metabolic Rates. The amount of oxygen you use once you have been asleep for a while. That's what the thyroid apparently controls in adult animals. Daytime won't do, that's probably under the control of something else. And peripheral temperatures. Not core. We're interested in the amount of heat flowing out of the body. Which is not quite the same thing as temperature....





Thanks to HungryHobo for making me make this point explicitly:

This is a very simple and obvious explanation of an awful lot of otherwise confusing data, anecdotes, quackery, expert opinion and medical research.

And it is obviously false! Of course medicine has tried using thyroid supplementation to fix 'tired all the time'. It doesn't work!

But there really is an awful lot unexplained about all this T4/T3 business, and why different people think it works differently. I refer you to the internet for all the unexplained things.

In just the endocrinological literature there is a long fight going on about T4/T3 ratios in thyroid supplementation, and about the question of whether or not to treat 'subclinical hypothyroidism'. Some people show symptoms with very low TSH values. Some people have extremely high TSH values and show no symptoms at all.

I've been trying various ways of explaining it all for nearly four months now. And I've found lots of magical thinking in conventional medicine, and lots of waving away of the reports of honest-sounding empiricists, who have made no obvious errors of reasoning, most of whom are taking terrible risks with their own careers in order to, as they see it, help their patients.

I've read lots of people saying 'we tried this, and it works', and no people saying 'we tried this, and it makes no difference'. The explanation favoured by conventional medicine strongly predicts 'we tried this, and it makes no difference'. But they've never tried it! It's really confusing. A lot of people are very confused.

I think that simple explanations are extra-worth looking at because they are simple.

Of course that doesn't mean they're right. Consequence and experiment are the only judge of that.

I do not think I am right! There is no way I can have got the whole picture. I can't explain, for instance 'euthyroid sick syndrome'. But I don't predict that it doesn't exist either.

But you should look very carefully at the simple beautiful ideas that seem to explain everything, but that look untrue.

Firstly because Solomonoff induction looks like a good way to think about the world. Or call it Occam's Razor if you prefer. It is straightforward Bayesianism, as David Mackay points out in Information Theory, Inference, and Learning Algorithms.

Secondly because all the good ideas have turned out to be simple, and could have been spotted, (and often were) by the Ancient Greeks, and could have been demonstrated by them, if only they'd really thought about it.

Thirdly because experiments not done with the hypothesis in mind have likely neglected important aspects of the problem. (In this case T3 homeostasis and possible peripheral resistance and the difference between basal metabolic rate and waking rate, and the difference between core and peripheral temperature and the possibility of a common DIO2 mutation causing people's systems to react differently to T4 monotherapy).

So that even if there are things you can't explain (I can't explain hot daytime fibro-turks...), you should keep plugging away, to see if you can explain them, if you think hard enough.

Good ideas should be given extra-benefit of the doubt. Not ignored because they prove (slightly) too much!






I reckon that we should be able to refute or strongly support the general idea from reports in the published literature. Here is some stuff that I have found recently. There is a comment that looks like this. Add anything you find to it, and I'll move it up here.


Found this for "Wilson's syndrome", but can only see the abstract:


It looks like it might be supportive, but it also looks crap. No mention of blinding, randomising, or placebo in the abstract.

Can anyone see the actual paper and link to it here? And can anyone work out whether these guys are allies of Wilson, or trying to break him? Because that matters.

This, on the other hand:


Looks solid, and looks like refutation. They claim normal average core temperatures in CFS. I have quibbles, of course:

I'd expect the core temperature to be well defended. So I'm not worried by that per se, but they do talk about relation to oral temperature, and they do talk about metabolic rate, so they've obviously thought about it, and I can't quite work out what they did there.

Also, the reason that they're measuring this is because their CFS patients have all been complaining about low oral temperatures and the fact that even when they've got a fever, they're not hot. So errr?? Do all the CFS patients believe this theory and are (un)consciously faking? I mean, I can believe that, but is it true that all CFS patients think this theory is true? Who is telling CFS patients to take their temperatures and why?

On the other hand, their actual graphs do look funny. There's a strange shape to the CBT vs time graph in CFS, but n=7, I think, so maybe that's just noise.

These guys:


Are actually claiming HIGHER peripheral temperatures in Fibromyalgia. But I think they're measuring during the day. I've no idea how to explain that, or what it might mean.

Barnes claimed: Measure axillary temperature on waking. Should be 98.6+/-0.2F (so 37C+/-0.1), lower is bad. Treat with lots of thyroid (1/2-2 grains).

I claim (from just me, and I am perfectly capable of fooling myself): measure oral temperature on waking. Was low (~36.1), has gone higher (36.6-7-8-9) under influence of small amounts of thyroid (1/3 grain). Feel fine now.

Can anyone find: Large numbers of CFS/FMS patients have normal metabolic rate while sleeping or just after waking, no exercise allowed, or normal axillary or oral temperature on waking, again no exercise allowed?

Because that's what I'm looking for at the moment, and it is refutation. I will have to pull off some clever moves indeed to get round that.

Oh, yes, and there's a paper by Lowe himself, finding exactly what I expect him to find:


Can anyone dig up quibbles with this that can make me discount it?

Oh Jesus:

Clinical Response to Thyroxine Sodium in Clinically Hypothyroid but Biochemically Euthyroid Patients G. R. B. SKINNER MD DSc FRCPath FRCOG, D. HOLMES, A. AHMAD PhD, J. A. DAVIES BSc and J. BENITEZ MSc Vaccine Research Trust, 22 Alcester Road, Moseley, Birmingham B13 8BE, UK

This I can't explain at all! He treated CFS people with tiny amounts of T4, and worked up the dose until they were all better. Worked a treat, apparently. Can anyone break it?

It simultaneously breaks me and proves that CFS is a thyroid problem. I think. Help! Again, no placebos, but a large clinical trial that seems to have worked, by a careful man.

I wouldn't dream of suggesting that anyone steal this using sci-hub.io by typing the title into the search box and then solving the easy CAPTCHA which is in English even though the instructions are all in Russian. You should write to the authors and request a copy instead.


Four 2003 Studies of
Thyroid Hormone Replacement Therapies:
Logical Analysis and Ethical Implications
Dr. John C. Lowe

Lowe again, my rationalist hero, publishing in his own journal, referencing his own papers and books. This time I think he's made maths mistakes. But that's my department, so I'm going to go away and think about it. I mention the paper here to avoid the obvious mistake of deciding whether to mention it after I've had a proper look.


Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia—A Randomized, Double-Blind, Placebo-Controlled, Intent-To-Treat Study

Jacob E. Teitelbaum*, Barbara Bird, Robert M. Greenfield, Alan Weiss, Larry Muenz & Laurie Gould


Background: Hypothalamic dysfunction has been suggested in fibromyalgia (FMS) and chronic fatigue syndrome (CFS). This dysfunction may result in disordered sleep, subclinical hormonal deficiencies, and immunologic changes. Our previously published open trial showed that patients usually improve by using a protocol which treats all the above processes simultaneously. The current study examines this protocol using a randomized, double-blind design with an intent-to-treat analysis. Methods: Seventy-two FMS patients (38 active:34 placebo; 69 also met CFS criteria) received all active or all placebo therapies as a unified intervention. Patients were treated, as indicated by symptoms and/or lab testing, for: (1) subclinical thyroid, gonadal, and/or adrenal insufficiency, (2) disordered sleep, (3) suspected neurally mediated hypotension (NMH), (4) opportunistic infections, and (5) suspected nutritional deficiencies. Results: At the final visit, 16 active patients were “much better,” 14 “better”, 2 “same,” 0 “worse,” and 1 “much worse” vs. 3, 9, 11, 6, and 4 in the placebo group (p < .0001, Cochran-Mantel-Haenszel trend test). Significant improvement in the FMS Impact Questionnaire (FIQ) scores (decreasing from 54.8 to 33.2 vs. 51.4 to 47.7) and Analog scores (improving from 176.1 to 310.3 vs. 177.1 to 211.9) (both with p < .0001 by random effects regression), and Tender Point Index (TPI) (31.7 to 15.5 vs. 35.0 to 32.3, p < .0001 by baseline adjusted linear model) were seen. Long term follow-up (mean 1.9 years) of the active group showed continuing and increasing improvement over time, despite patients being able to discontinue most treatments. Conclusions: Significantly greater benefits were seen in the active group than in the placebo group for all primary outcomes. An integrated treatment approach appears effective in the treatment of FMS/CFS.

OK, how do we discount this one? I haven't even read it yet. Can anyone see it?

Thyroid Insufficiency. Is Thyroxine the Only Valuable Drug?


W. V. Baisier, J. Hertoghe & W. Eeckhaut

Purpose: To evaluate the efficacy of a drug containing both liothyronine and thyroxine (T3 + T4) in hypothyroid patients who were treated, but not cured, with thyroxine (T4 alone). Design: Practice-based retrospective study of patients' records. Materials and Methods: The records of 89 hypothyroid patients, treated elsewhere with thyroxine but still with hypothyroidism, seen in a private practice in Antwerp, Belgium, were compared with those of 832 untreated hypothyroid patients, over the same period of time (May 1984-July 1997). Results: The same criteria were applied to both groups: a score of eight main symptoms of hypothyroidism and the 24 h urine free T3 dosage. The group of 89 patients, treated elsewhere with T4, but still complaining of symptoms of hypothyroidism, did not really differ from the group of untreated hypothyroid patients as far as symptoms and 24 h urine free T3 were concerned. A number of these patients were followed up during treatment with natural desiccated thyroid (NDT): 40 T4 treated patients and 278 untreated patients. Both groups responded equally favourably to NDT. Conclusions: Combined T3 + T4 treatment seems to be more effective than treatment with T4 alone in hypothyroid patients.

Even mighty sci-hub.io can't provide me a copy of this. Any reason to bin it?


Bored now. Anyone find me anything that says this doesn't work?

I've even heard rumours that Lowe himself did PCRTs of his treatments. And probably published them in some chiropractic house mag. I can't even find those.





A rich seam of thyroid vs depression papers, all found through: http://psycheducation.org/

Since he's got a cause, I expect to find them all in favour. I'm going to list them here before reading them in order to avoid the obvious mistake of cherry picking from the cherry basket, and then add comments once I've read them / their abstracts.

Further evidence pointing in the opposite direction is very welcome!

I also tried:

and some of those are also here. I can't remember which ones I found through psycheducation and which ones through pubmed.
Bloody browser tabs, sorry, I should have been more careful.

J Affect Disord. 2014 Sep;166:353-8. doi: 10.1016/j.jad.2014.04.022. Epub 2014 May 2.
A favorable risk-benefit analysis of high dose thyroid for treatment of bipolar disorders with regard to osteoporosis.
Kelly T1.



High dose thyroid hormone has been in use since the 1930s for the treatment of affective disorders. Despite numerous papers showing benefit, the lack of negative trials and its inclusion in multiple treatment guidelines, high dose thyroid has yet to find wide spread use. The major objection to the use of high dose thyroid is the myth that it causes osteoporosis. This paper reviews the literature surrounding the use of high dose thyroid, both in endocrinology and in psychiatry. High dose thyroid does not appear to be a significant risk factor for osteoporosis while other widely employed psychiatric medications do pose a risk. Psychiatrists are uniquely qualified to do the risk-benefit analyses of high dose thyroid for the treatment of the bipolar I, bipolar II and bipolar NOS. Other specialties do not have the requisite knowledge of the risks of alterative medications or of the mortality and morbidity of the bipolar disorders to do a full risk benefit analysis.

J Clin Endocrinol Metab. 2010 Aug;95(8):3623-32. doi: 10.1210/jc.2009-2571. Epub 2010 May 25.
A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham Elderly Thyroid study.
Parle J1, Roberts L, Wilson S, Pattison H, Roalfe A, Haque MS, Heath C, Sheppard M, Franklyn J, Hobbs FD.


This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function.






J Affect Disord. 2002 Apr;68(2-3):285-94.
Effects of supraphysiological thyroxine administration in healthy controls and patients with depressive disorders.
Bauer M1, Baur H, Berghöfer A, Ströhle A, Hellweg R, Müller-Oerlinghausen B, Baumgartner A.

J Affect Disord. 2009 Aug;116(3):222-6. doi: 10.1016/j.jad.2008.12.010. Epub 2009 Feb 11.
The use of triiodothyronine as an augmentation agent in treatment-resistant bipolar II and bipolar disorder NOS.
Kelly T1, Lieberman DZ.

Am J Psychiatry. 2006 Sep;163(9):1519-30; quiz 1665.
A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report.
Nierenberg AA1, Fava M, Trivedi MH, Wisniewski SR, Thase ME, McGrath PJ, Alpert JE, Warden D, Luther JF, Niederehe G, Lebowitz B, Shores-Wilson K, Rush AJ.

Nord J Psychiatry. 2015 Jan;69(1):73-8. doi: 10.3109/08039488.2014.929741. Epub 2014 Jul 1.
Well-being and depression in individuals with subclinical hypothyroidism and thyroid autoimmunity - a general population study.
Fjaellegaard K1, Kvetny J, Allerup PN, Bech P, Ellervik C.

Mol Biol Rep. 2014;41(4):2419-25. doi: 10.1007/s11033-014-3097-6. Epub 2014 Jan 18.
Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder.
Berent D1, Zboralski K, Orzechowska A, Gałecki P.

Mol Psychiatry. 2016 Feb;21(2):229-36. doi: 10.1038/mp.2014.186. Epub 2015 Jan 20.
Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.
Bauer M1,2, Berman S2, Stamm T3, Plotkin M4, Adli M3, Pilhatsch M1, London ED2, Hellemann GS5, Whybrow PC2, Schlagenhauf F3.

Mol Psychiatry. 2005 May;10(5):456-69.
Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression.
Bauer M1, London ED, Rasgon N, Berman SM, Frye MA, Altshuler LL, Mandelkern MA, Bramen J, Voytek B, Woods R, Mazziotta JC, Whybrow PC.

Minerva Endocrinol. 2013 Dec;38(4):365-77.
Hypothyroidism and depression: salient aspects of pathogenesis and management.
Duntas LH1, Maillis A.

J Psychiatr Res. 2012 Nov;46(11):1406-13. doi: 10.1016/j.jpsychires.2012.08.009. Epub 2012 Sep 7.
The combination of triiodothyronine (T3) and sertraline is not superior to sertraline monotherapy in the treatment of major depressive disorder.
Garlow SJ1, Dunlop BW, Ninan PT, Nemeroff CB.

Mol Psychiatry. 2016 Feb;21(2):229-36. doi: 10.1038/mp.2014.186. Epub 2015 Jan 20.
Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.
Bauer M1,2, Berman S2, Stamm T3, Plotkin M4, Adli M3, Pilhatsch M1, London ED2, Hellemann GS5, Whybrow PC2, Schlagenhauf F3.


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Thanks for working this up. I remember reading somewhere that thyroid tests were unreliable, and it think it was because they're just checking hormones in the blood rather than whether the hormones were being used.

Hi, I just read your posts from 5 yrs ago. How is your health and might you have any more insights into discussed conditions? I'm one of those old women (described in your writing) am thought to maybe have Long COVID (no test August 2020 here in Northern Ireland) or 'post-viral with neurological overlay...' currently due to have brain/spinal MRIs. I really enjoyed your ideas especially stuff on thyroid etc I think I present as M.E./CFS and have no answers. All good wishes and thanks. (As thinking is tricky I mostly listen to books so if you have a recommendation, cool).

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 bi
Your explanation of the chronic tiredness as a 'stuck immune response' or inability to completely clear the virus is useful to consider.
Thanks, again for your thoughts and experience. I had AZ first dose (April 2021), 12 hrs later back to severe headaches- like headaches experienced during unknown virus (August 2020) plus shaking from head to toe for under 3 hrs- I was fine within two days, just tired. As I continued to be extremely fatigued etc by time second AZ appointment came, given more info on rare blood clots, I did not take second AZ, but (another month later) had a Moderna and will take second Moderna. Given how ill I've been for a year I guessed that I'd be better with an Mrna as opposed to adenovirus vacc. First Moderna left me with a sore arm, slight sore throat and tired - none of the extreme pain & shaking of AZ. Maybe I'll react to the second Moderna...It seems to me that insights into ME/CFS and Long COVID, here in the UK, are few. I will read your posts & comments again, and look further into treatment for thyroid. Thanks, it is good to hear that you found a route to wellness.

To increase the credibility of the article, IMHO you need to ditch pretty much the entire "SOME SELECTED POSSIBLE IMPLICATIONS / PREDICTIONS" section. Reading through that, it sounds very much like you're trying to solve unrelated problems with your newly found hammer:

Dieting - you're not really predicting anything here. Turn it into a prediction of some sort or it's just dead weight.

Diabetes - you've got no evidence for any kind of common hormone suppression mechanism, and my understanding of how hormone chemistry works places the probability ... (read more)

Thanks ever so much for your careful reading and criticisms, but I'm trying to do philosophy correctly here, according to my own ideas of what philosophy should be. Extremism in thought-experiment is no vice. I have mentioned these harmless conclusions in order to get people to think that the idea might be more important than it seems on the face of it. If they make me easier to refute or disbelieve, that is a good thing. If you have the right sort of friends, approach them with whatever version of this argument you think you need to get them to think about it. If they can think, they will draw all my conclusions for themselves in a few weeks. If they can't, I don't care about their opinion, there are plenty like them in the world, they will believe whatever someone eminent tells them is true, as long as it is not too scary. [That's not a bad heuristic, that's what I mostly use too.]
My apologies, I misread your intent. I thought that you were attempting to get feedback on what appears to be a viable hypothesis for improving the lives of a large number of people with debilitating diseases. I thought you were lining up ducks, proofing your arguments, improving probabilities, and investigating attack vectors to possibly make the world suck less. I thought you were trying to Win :P In this, for me at least, you have succeeded. However, you have not (yet) made a convincing enough case for me to burn my resources pushing it. This is a low probability, high reward scenario. Convince me that this is worth dropping other important things, as my time is limited. If your plan is to Win, and in order to Win you need to convince others, then it is a very dangerous, risky, and often counterproductive strategy. I not only have the right sort of friends, I have the sort of friends that are in the "someone eminent" category that could help your idea gain significant traction. However, those friends have massive demands on their time, and none are so superhuman that they could investigate every probable idea. Do I ask a friend to drop work on treating respiratory disease with ChlorHex oral rinse to investigate your idea? Can I in good conscience argue that it would be worthwhile? At the moment, I cannot. So again, what is it that you're trying to do? This topic is clearly near and dear to your heart, and you've got a workable combination of incentive and intelligence to make sure this gets investigated fully, for better or for worse. However, the road is long and arduous, and it will likely require you to interface with others and swallow your pride if you truly want to Win and succeed. On the other hand, if you just want to philosophize, then by all means carry on.
OK, you are right, of course. Although I must say my primary motivations do seem to be curiosity, fixing myself, and unreasoning rage on behalf of the scientific method. The whole 'curing millions' thing doesn't really get me in the same way. Which is lucky, because if I wasn't protected by galloping scope insensitivity I'd go completely mad. I had a bit of the 'total perspective vortex' effect during my manic episode, and I never ever want to feel like that ever again. I kept reading the narrative of Vicky Rippere, and crying for that brave and clever young woman and for what was happening to her. But it seems that the principal difficulty here is to convince myself to take the idea seriously enough to get political. And obviously you have the same trouble. It is an obvious crank-trap. A hidden disease that can pretend to be lots of other diseases, that the standard tests don't work for. Come on... And so I am all Pascal's Wager at the moment, and I keep thinking Atlantis, Pyramids, Atomism, Catholicism, Non-euclidean geometry, golden ratio, spiritualism, heliocentric theory, squaring the circle..... All obvious ideas that are hard to prove or refute and which drove men mad for hundreds of years. The obvious strategy is to take this latest version of the madness to the sufferers' groups, and unite them into one huge angry movement that will force medicine to refute the damned thing properly. But I will cause vast harm doing that, and if I am wrong, which has to be the case, then no good will come of it. One's first duty is to do better than Hitler. And at the moment, I feel that it is the right strategy to hide behind the very ludicrousness of the idea. I am hypothesising what I am hypothesising. No lesser version can be true, that I can see. It has ghastly consequences. If that keeps incurious people away, good. Don't persuade your eminent friends to drop everything. That would be silly of them, and I would feel guilty. Get drunk with them, and say: "I was

I've had some large fluctuations in my thyroid levels, which have prompted me to develop a better understanding of thyroid problems than I had when this post was published.

I agree with a fair amount of this post, and I'm uncertain about a few of the claims it makes.

I agree that hypothyroidism is undertreated, and likely overlaps with CFS.

I think our prior should be that CFS has multiple causes, and that we shouldn't expect to find a single solution to all CFS. It's easy to find other conditions that have multiple causes. E.g. depression can be caused by hy

... (read more)

Disclaimer: Only spent 20 minutes on this, so it might be incomplete, or you may already have addressed some of the following points:

At first glance, John Lowe authored 2 pubmed-listed papers on the topic.

The first of which in an open journal with no peer review (Med. Hypotheses) which has also published stuff on e.g. AIDS denialism. From his paper: "We propose that molecular biological methods can provide confirmatory or contradictory evidence of a genetic basis of euthyroid FS [Fibromyalgia Syndrome]." That's it. Proposing a hypothesis, not pro... (read more)

j'y trouve beaucoup de mal, je vous assure..... I mean crank-a-rama, signs-wise. But actually, what I've read of Lowe reminds me of me. He's obviously trying to prove something that he's convinced is true, and I can well believe that he's self-deceived. But I have trouble believing that he was a liar, or a serial murderer of his patients. And if he wasn't that, then he must have been right about the peripheral resistance. A lot of what he's writing looks like spectacular pedantry, which can only come from a really motivated thinker trying to force his hypothesis through the sieve of the inconvenient facts. And it doesn't half remind me of a mathematician trying to prove a tricky theorem that he knows is likely true because he's checked a million cases by computer and it's either true or false for subtle reasons. So you keep trying to force the proof through, and the places you fail give you ideas for why it might be false in some unexpected way. So you look in those places, trying to find why it's false, and when you can't prove it's false either, you go back to trying to show that it's true in spite of those failures. And eventually you either show it's false, or you show it's true. And you're allowed to use any method you like to work on it, as long as at the end, you've either got proof or counter-example. It turns out Lowe's hobby was mathematical logic. I keep thinking that if it had been probability theory, he might have nailed it before he died. I really really wish I could talk to him. Bad death. That's another thing we should sort out, once we have sorted this. I think it's typical of Lowe to have gone looking for something, and found the opposite, and then published anyway, and then tried to force his ideas through in spite of what he found. It's just that my professional training, such as it was, tells me that that's how you find out the truth. ---------------------------------------- And of course, I'm not depending on Lowe. He told me where to

Pre-registration of n=1 insane self-experiment.

Blood tests back, blood drawn at time of highest 'manic episode' (24th Feb), 24mg/desiccated thyroid/day.

TSH 2.31 [0.35-5.5]

Accursèd lab at Addenbrookes' this time tested T4: 13.1 [10.0-19.8] but did not test T3, despite GP's firm request for T4,T3 IRRESPECTIVE OF TSH

Perfectly consistent with thyroid dialling back to compensate for NDT, T3 level too high, T4 level too low, which was my prediction. I'd have expected T3 to be at the top or out of its normal range. Perfectly consistent with Ken Blanchard's idea t... (read more)

Internal bleeding? Is there any blood in your urine or excrements?
Not that I've noticed. Reminds me of the joke about the three mathematicians and the sheep.

As I said in another comment, it sounds extremely plausible to me that CFS is mainly caused by a viral infection doing damage to one of the hormone glands in the HPA-axis. Nothing else out there makes any sense and I'd bet at 40% that the HPA-axis is what's wrong with CFS sufferers.

The question is, what can we do about it right now? The medical establishment has already lost interest in doing anything about CFS. I am not a medical researcher, I don't have loads of money either.

Perhaps interested people here on LW can form a startup-style charity to try and investigate this? I'd be up for chatting over skype or something.

There is no 'medical establishment'. There are people trying to work out where their limited amounts of money should be best spent. http://www.mrc.ac.uk/funding/science-areas/population-systems-medicine/cfsme/ £1.6million is not much, for the scale of the problem, but I would not put my rational charity dollar into CFS funding, or indeed into any first-world medical problem, and I actually have some chance of being a sufferer.
It seems to me a lot of the problem is due to it not being a clear diagnosis. Especially one that can be easily and objectively measured. If johnlawrenceaspden thesis of a lower core body temperature is true, that might advance the field by providing an easier way to test for CFS. Maybe there should be a suppository that continously measures bodytemperature and acceleration.
No! Not lower core body temperature! That's a mistake everyone involved keeps making. Low basal metabolic rate. I.e. after you've been asleep for a long time. Which Barnes claimed was best measured by waking armpit temperature. Lots of papers saying thyroid hormones correlate with basal metabolic rate in animals. But not with 'field metabolic rate'. That's probably controlled by other hormones or the nervous system. And core temperature is likely well defended. But basal metabolic rate has to correlate well with skin temperature (in equilibrium in a constant temperature known humidity environment, etc), because physics.
I think you would likely get a better measurement with 24/7 temperature measurement than simply measuring waking temperature on one spot.
The other option is to directly measure basal metabolic rate while sleeping. That might be easier to do as a home thing these days. Barnes had to get people to go to the testing centre and then be scared stiff by complicated apparatus. They got all panicky and screwed up the test. But if there's some way of measuring BMR while sleeping in your own bed and you can do it every day for a week until you stop getting nervous, that looks like it would be sound.
Agreed. Some sort of 24-hour continuous thermometer attached while you slept might be good. And ideally you want to measure skin temp and outside temp, since what we're interested in is the amount of heat passing through your surface, not your temperature per se. But Barnes reckoned axilliary waking temperature was the best test, and he was a proper endocrinologist with access to whatever tests he wanted, and he looked at lots. And everyone thinks he was a loony because he said hypothyroidism was really common and explained everything. And I did too until I realised I'd just predicted the same thing from the simplest explanation for my mystery.
That's interesting. There might be some smartwatch that can measure skin temperature on the arm.
Sarah Myhill has an excellent test for CFS, which can tell you not only whether you've got it but how strong it is. I like her paper. She is lying, or she is right. If we can correlate that with Barnes' waking-armpit-temperature thingy then I think I just buy the whole thing. If we can't, I think I have to give up with the 'occult hypothyroidism everywhere' already and retreat to 'something funny about those tests, a few cases missed, maybe'
That's a pretty strong statement. What makes you believe that it can only by one of those two cases? Apart from that I'm not even sure whether she believes that she has an excelent test given that she writes: There is no simple test currently available to diagnose CFS because, as I have said already, CFS is not a diagnosis – it is a symptom.
Because her evidence is very strong. She hasn't got it by luck or a bit of innocent p-hacking. Her test score correlates very nicely with her assessment of severity of symptoms. I think in the quote she's saying 'I wouldn't diagnose someone with CFS, that's what they present with, my test is for mitochondrial dysfunction and that can be a cause of those symptoms, but so can e.g. lack of sleep or bad diet or hypothyroidism'. But I don't know. Of course I think that hypothyroidism can cause mitochondrial dysfunction. Everyone involved is using words differently, and that's obviously confusing, but I think we have to avoid getting hung up on it and try to look for the predictions we have in common and our ways of carving reality up.
That reminds me of Jay A. Labinger: The language you use to talk about something influences the way you think about it. If the chemistry you’re talking about is truly something new, then a fight over terminology may be quite an important part of getting to understand that chemistry better. Mitochondrial dysfunction might be a much better disease target than CFS.
Absolutely. We need to 'carve reality at its joints' (may his name be praised), and naming things is important, whatever St Feynman said. But it is ever so important not to get into pointless bunfights about words.
Fights about words are not pointless. Finding the right words is important to understand unclear territory. Getting clear about words allows to make more precise statements.
Agreed, let us not get into a pointless meta-bunfight
Gland damage would show up on hormone blood tests. Does CFS always start with an infection? Are there any particular suspect pathogens? Lyme Disease? Any others? If it is an immune response then it could be triggered by a whole host of different little horrors. Whatever's wrong with me came on slowly over months and initially presented as long sleeping and bad hangovers, followed by alcohol aversion. (I assume I was learning to avoid it) One of the major differences NDT made to me is that I went from '2 pints gives me a three day hangover' to 'a huge session makes me feel slightly woozy the morning after'. I did get a tick bite years ago, but there was no sign of Borrelia Burgdorferi either then or now. I did read a paper a while back claiming that there must be a second cryptic pathogen from ticks, because the symptoms often appear without the spirochete. All that might be worth a look. ---------------------------------------- EDIT: Actually that's not true, according to my own blog: http://johnlawrenceaspden.blogspot.co.uk/2012/09/ok-nhs-is-brilliant.html At the time I wrote that there was a bloody great rash. But the test then didn't show the infection, and this summer's tests didn't show it either.
Jaded One, why do you think adrenal rather than thyroid? And how does adrenal fit with Sarah Myhill's CFS/mitochondrial dysfunction thing? I am not interested in being part of a sufferer's group. The last thing I need is a like-minded echo chamber to preach to.
No, I didn't mean a "let's meet for tea and share sob stories" group, I meant if we had 3-4 talented individuals with CFS and a pro-rationality mindset, it may be worth trying to see whether we can easily nudge the medical community into trying to seriously investigate the HPA/thyroid angle on CFS. I'm open to the possibility that the thyroid could be the main locus of the problem. At some point, the world will work out what causes CFS. Medicine is entering a highly data-driven era and this disease will leave evidence scattered around the epigenome, gene expression levels, hormones, etc. Eventually all people in the developed world will have devices implanted to measure all this stuff and it will be analysed and the correlations will be exposed. However, my lifetime is not infinitely long, so if I can hasten that point relatively cheaply, I want to do so.
Pah, where is your ambition?
Well, it's infinite in expectation, but under many scenarios I will end up dead and/or thawed.
Ah, OK, well, that is what I am trying to do. And at the moment my principal difficulty is that I don't believe it myself. I reckon if I can grub up enough evidence to make myself believe it then making medical types believe it will not be too hard. So if you'd like to join the effort, go scour me the medical literature for evidence that Central Sensitivity Syndrome sufferers have low basal metabolic rates, endocrine hormone resistances, or low peripheral temperatures after they have been asleep for a long time. Or evidence against any of those things. There is no point wasting anyone's time with a good idea that is false. Google Scholar, Pubmed (http://www.ncbi.nlm.nih.gov/pubmed), and sci-hub.io are very useful, as is membership of a university which subscribes to journals. But even better if you can think of tools I'm not using. I am new to this. When I were a lad you had to write to the authors if you wanted a copy. And if you find an interesting paper, you can look on google scholar for other papers citing it, and see what they say. That is the sum total of my search skillz. I need the help of a proper academic. And by the way, I don't actually think I've got CFS! It's just one of the possibilities. But I see people claiming the glory of physics without using the methods of science. And for some reason I find that very motivating.
Sure, that's one thing that might help. On the other hand it may not be the most effective way to hasten the curing of CFS/FM; it's privileging one specific hypothesis a bit too much for my liking. I am convinced that CFS is caused by some problem with the HPT/HPA-axis, and I am extremely confident that it is a real physical condition triggered by a viral illness. Beyond that I don't want to commit too much. Medical research is time-consuming and expensive, but on the other hand there are approx. 1 million confirmed CFS sufferers in the developed world, with a penumbra of probably 1-10 million undiagnosed. That's a lot of people. Some of them are very rich or have very rich parents, and pour huge amounts of money into attacking the disease, often not applied in the most effective ways. In addition, those who advocate for medical CFS research have pretty poor rationality skills. They cling to any hope of a biological cause, beyond the point where it is rational to support a given specific biological cause, and make death threats against researchers who provide any disconfirmatory evidence against specific hypotheses. It's a bad situation; huge resources, huge numbers of sufferers, potentially lots of money to be marshalled, but no competent organization. You and me sitting at our computers reading pubmed abstracts may not be the most effective attack against the disease. Maybe we should be trying to mobilise and coordinate existing money and resources more effectively? Maybe we should try to set up a "CFS biological diagnostic test prize", in the style of X-prizes? Then this would incentivize people who are professional biomedical researchers to do the hard work for us?
That seems like a good idea. I don't think it's a project I would want to do full-time, but I would be willing to be involved.
That's cool. Maybe we should set up some kind of information sharing system like an email thread or a new top level post here on LW?
Wow, I was completely unaware of all this: https://en.wikipedia.org/wiki/Whittemore_Peterson_Institute#History I thought people just pretty much ignored CFS and put it down to lead-swinging. All that fits in rather nicely, though, doesn't it? What else do you know that I don't know?
Further googling around uncovered these guys: http://simmaronresearch.com/about/
Well I've done some research into organizations and followed the news over the years, done some googling. It seems to me that CFS research has not focused enough on exploratory research looking to track down the root cause of the illness with an open mind to all biological causes. Lots of time and effort is wasted waging a pointless argument about whether the illness is psychosomatic or not, rather than accepting that it is biologically caused and looking for the cause. Time, money and effort is also wasted trying to find treatments for an illness whose etiology is unkonwn.
I am not a political man, I am trying to do a bit of harmless philosophy as a hobby. If you can mount a political attack, go for it. I would be a rubbish politician.
Also, I'm currently thinking, thyroid controls basal rate, adrenal controls rate minute-by-minute. So stick to your guns, adrenal wise, and tell me the obvious things I've missed.

This is very interesting, particularly the person account of self-experimentation but may I suggest that if you want people to listen seriously it's best to keep your claims minimalist.

"a possible palliative for some cases of Chronic Fatigue Syndrome" : excellent.

"and a panacea for most of the remaining unexplained diseases of the world." : makes me immediately view the rest skeptically.

Attributing a large fraction of the worlds health ills to a single cause, even if only speculatively is a little bit of a red flag for crackpotism so... (read more)

Your advice is sound politically, but the proposed action strikes me as intellectually dishonest. I am hypothesising what I am hypothesising. It is pretty much grail or nothing. Making myself harder to refute won't help.
In general minimalist predictions are more often true than complex predictions that try to explain everything and the kitchen sink. We have cognitive biases that make us want to prefer the complex predictions.
I'd have to make my hypotheses more complicated in order to explain less. That might make them more believable, and less open to refutation, but I think it makes them less likely.
No. You wrote: Somewhere between a possible palliative for some cases of Chronic Fatigue Syndrome, and a panacea for most of the remaining unexplained diseases of the world. If you would simply leave out the bit about most of the remaining unexplained diseases of the world and would focus on CFS and fibromyalgia the thesis would get simpler.
But I need to hypothesise 'widespread occult hypothyroidism', and that disease has many more than two presentations. It would have trouble causing CFS/FMS without also causing IBS, for instance, and I think there are many others that are just reshufflings of the same symptoms.
Ok, look at chiropractors. There are 2 schools of chiropractors. (ok, more but for this we can think of 2) One who say "the body is reeeeaaallly complex but sometimes pushing and pulling the bones/muscles in the back around can help with back pain and sometimes can help with trapped nerves" This is complex. It treats it as a complex problem where the intervention can help with a small subset of cases. Then there's the other group who have a really simple hypothesis that health problems are caused by disruptions to the flow of "life energy" to parts of the body and and claiming that we need to They attribute almost all health problems to disruptions to the flow of energy. This is really simple. But simple(to say) does not mean correct. Historically most people who attribute too many health problems to a single cause are quacks so if you want to be taken as a non-quack then you're better off limiting your claims.
But I only want to be taken seriously if I'm right! If I'm wrong then it's much better if people think I'm a lunatic. Both of your chiropractic hypotheses make the same (i.e. no) predictions about back-pain. The simplest chiropractic hypothesis is the second one. Thus in the absence of any other evidence, consider the second one. It's actually not a bad hypothesis. Replace 'life energy' with 'blood' to see why. But once you've said blood then it makes testable predictions. And can be refuted. My hypotheses are about real, testable things. I have made several testable predictions. And there are many more, that are obvious if you think about it for a minute. I argue that they should be tested. That is all I argue. I will accept as strong relevant evidence anything you can drag up from the medical literature that shows people taking the idea of 'type 2 hypothyroidism' seriously, or any evidence about basal metabolic rate in chronic fatigue or fibromyalgia. Or any other good argument that anyone can make. Where do I err, brother philosopher? ---------------------------------------- EDIT: changed 'first' to 'second' below, and vv. Thanks HungryHobo. I am a fool. As to actual chiropractors, obvs the second school are not paying nearly enough attention to this 'life energy' as they claim to think it deserves. That makes them magical thinkers. And the first school are having a solid pop at empirically working out some helpful techniques. The first type of chiropractor is in the church of science. St. Feynman would approve. Endocrinology is not. For all their white coats, and all their pompous arrogance. They are not.
Which would be lovely if they actually claimed that this "life energy" was blood. They do not. The first group of chiropractor has an evidence base and their limited claims actually work out in the real world and are very close to orthopedics. The second is nowhere near the "church of science" and have little interest in it. Science is not about your hypothesis sounding poetic.
I am so sorry. Where I erred was to get 'first' and 'second' the wrong way round. I think we agree about most things, and I am going to change my parent comment so that it says what I meant when I wrote it. ---------------------------------------- But we still disagree about poetic hypotheses. I think that simple explanations are extra-worth looking at because they are simple. That doesn't mean they're right. Explanatory power and prediction and experiment are the only judge of that. But you should look very carefully at the simple beautiful ideas that seem to explain everything, but that look untrue. Firstly because Solomonoff induction looks like a good way to think about the world. Secondly because all the good ideas have turned out to be simple, and could have been spotted, (and often were) by the Ancient Greeks if only they'd really thought about it. Thirdly because experiments not done with the hypothesis in mind have likely neglected important aspects of the problem. (In this case T3 homeostasis and possible peripheral resistance and the difference between basal metabolic rate and waking rate, and the difference between core and peripheral temperature and the possibility of a common DIO2 mutation causing people's systems to react differently to T4 monotherapy) Good ideas should be given extra-benefit of doubt. Not ignored because they prove too much! ---------------------------------------- Actually I think all that is worth adding to the main post, so thank you very much!
Why? The situations where mechanism X works for some people some of the time are very common.
Sorry, I mean, grail as in all the central sensitivity syndromes, not grail as in all sufferers of those syndromes. ---------------------------------------- Of course, that would be a priori unlikely. Now we need occult hypothyroidism plus a complicated way in which something that's nothing to do with thyroids causes thyroidy symptoms. A bit like proposing that one of the twin towers was destroyed by the CIA, while at the same time, terrorists destroyed the other one. Or for that matter, the decisive argument in the Amanda Knox case.

Post 2 of 3 was virtually ignored; post 1 got a lot of votes. My guess is no one with a modicum of medical knowledge has looked at it, so they up voted to increase the post's visibility because you're open to criticism and they're curious, then they had no reason to up vote the second time. Like CronoDAS said, it would be cool to have Sarah Constantin look at this. Or maybe Scott Alexander, though he's not an endocrinologist.

This also seems like exactly the sort of thing NancyLebovitz has been looking for.

I'm pretty sure someone asked Scott on tumblr for his opinions on the first post. I think his reply was something like, "seems plausible but not my area of expertise", but I can't find it now. edit: I just scrolled through seventeen pages of his tumblr (until I got to before the first one was posted) and didn't find it. I could have missed it, but this decreases my confidence that it happened.
Yes he said it could be plausible but would require more work to form better thoughts on.
Scott and I were in communication earlier, and he asked some good questions that provoked post 2. Now he's not talking to me. Not sure why. ---------------------------------------- Just really busy, apparently.
I honestly want to know - what do you expect him, or someone here to do? Say you're right? Figure out a way to fund a clinical trial of FM patients treating them with T3 or pig's thyroid? (I admit I didn't read all of your posts from beginning to end, you said that such trials were already done? If that's the case are they good quality? If this is such miracle treatment then were the results not clear?) If you want to convince anyone, then you need interventional data, not hypothesizing. In other words, you have to pony up, or convince someone to pony up and fund said research.
I want him, or anyone else, to show me things that I haven't thought about, or have just missed, that mean I'm wrong. If I wanted disciples, I know exactly where to find them. It is a core belief of this website that one is very bad at seeing the evidence against one's own ideas. I believe in that. I am asking people to take me down, because I am probably unable to do that for myself, and I do not want to cause a catastrophe while I am still dithering, but if I just dither secretly, all I will do is find more evidence in favour. ---------------------------------------- This seems like the entire problem. How to convince people to do the expensive experiments needed to explore the obvious hypothesis, without already knowing the answers? Physics will spend billions trying to find surprises, for the sheer joy of it. In medicine, where millions of lives may hang in the balance, no one cares.
Get an MD, prescribe pig's thyroid if you really believe it such a fantastic treatment. If the evidence is clear, start a clinical trial. Admittedly, I don't know if you can do that in the the nationalized UK health system, if you're in private practice in the US I believe you have enough leeway to do that. You'll be under very heavy scrutiny though, and there may be insurance issues but I don't understand them well. As to what you're missing? It's really simple - you have an interesting hypothesis and not much else. And you have almost no quality data to back it up. Without that, there is nothing there to criticize. Your single case of pig's thyroid working is the most interesting evidence to me, however, personally I would bet on FM and the other somatoform disorders having heterogeneous causes (they aren't the same disease in every person). For example: http://www.medscape.com/viewarticle/761364_3 I'd be surprised if pig's thyroid cured a mitochondrial myopathy. Also, the reason why expert' aren't taking you seriously, is that you kind of sound like a crank. A very intelligent crank admittedly, but a crank nonetheless. It's not that you have lots of facts wrong, it's more subtle than that, and I'm afraid it's hard to explain. Statements like this slightly exaggerated reaction Erm what? No they aren't extremely similar, and that's not even logically correct, rejecting 2.1 doesn't entail accepting 2.2 at all. And why is diseases having similar presentation a grand revelation? Do you know anything about the rest of medicine? Differential diagnoses based on a clinical picture are the rule not the exception. I'm sorry if that's sounds harsh, but I'm trying to convey the attitude that someone who is in the field might have towards you. You don't quite speak the language. To use an analogy - you know the words but you have funny accent.
No worries about sounding harsh! I declared Crocker's Rules, so I'm explicitly asking you to optimise for communication and not worry about offending me. And I very much appreciate you taking the time to tell me things I don't know. That's exactly what I'm saying! The action of T3 seems to be to control ATP recycling in the mitochondria. Sarah Myhill's beautiful paper to my mind proves almost beyond doubt that that's the problem in CFS. This is what I mean by 'every time I look for disconfirming evidence, I find new reasons to believe'. I know that I sound like a crank. That's because I am a crank. I am a member of several at-risk groups for Arrogant Overconfidence Disorder, which I strongly suspect to be related to hypothyroidism in some way. Others have suggested that I am under a certain amount of 'stress'. CFS/FMS and hypothyroidism are much more similar than most diseases, to the point where out of a fabulous number of possibilities I was trying to fit to what was wrong with me, hypothyroidism looked instantly like what I had, despite the fact that I'd not only had the test for it, but the test was bang in the middle of the normal range. And I think the CDC agree. One of the diagnostic criteria is explicitly that hypothyroidism have been ruled out (haven't checked this, just a memory). But also, doesn't the fact that all diseases look similar strike you as suspicious? As I understand it that was the whole reason for the 'stress' theory in the first place. Let me think about the logic for a while, I'll get back to you. ---------------------------------------- OK, logic looks fine. I really need to know if that bit's wrong. It means my mind is broken. If they're not differently caused then they have the same cause. And if that's true, then in one case the TSH test is picking it up, and in the other it's not. So the test is not doing what it's supposed to. ---------------------------------------- Suppose diabetes was diagnosed by insulin levels instead o
It seems I somewhat misunderstood your argument and misjudged you; I tentatively pegged you as a pig’s thyroid evangel feigning humility. I apologize. I also apologize because I am not the opponent you are looking for. Since I apparently didn’t stress this enough, I will conclude by saying again that without interventional data, you have nothing. It doesn’t matter how beautiful your theory is, it doesn’t matter how smart you are, if it disagrees with experiment then its wrong. Repeating your hypothesis again and again, doesn’t help your case, it hurts your credibility. Unfortunately this is all I have to offer that I think is worth offering at this point.
That is not true. You would prefer to have data from randomized intervention trials, but even without them you can look and collect data and come to conclusions.
My dear old thing! That is a perfectly natural assumption to make and there is no need to apologise. If I were convinced of the truth of this idea, that is likely exactly what I would be, here practising the argument before I have to make it as a wild-haired prophet. But I think I have managed to retain enough sanity to not want to believe it if it's not true. And I have pretty high standards for truth, and they definitely include intervention, cause, randomisation, placebos and control. At the moment, I think that my hypotheses are probably false (because there is no way that I can see that it can be a widespread problem and yet fibro-turks are hot) If it's false, then I think it's probably important to refute it properly if only to stop Wilson. But I don't care very much about that. My own problems seem to be gone, they are or were probably either non-existent or horribly idiosyncratic and no one can help me with them, and I am just going to have to work it out on my own. That's a man's death and I am glad to have found a worthwhile enemy. But I disagree with you about beautiful hypotheses. If they disagree with experiment then they are wrong, no question. But they are worth looking at carefully, and a science that does not bother is not a science. And probably not truth-finding, even over the long run. If you run into any interested opponents, do tell them there is someone wrong on the internet. There is still a mystery to explain! It's just back to being a hobby, for me.
Today we have people saying that cancer isn't a single illness and people trying to make distinction within broad categories of illnesses. I think there's a good chance that depression isn't a single illness and a lot of our present disease categories aren't.
No, not in general. It might be for diabetes, but that's fact-specific. Let's try substituting in something else: Suppose fractured skulls were diagnosed by X-rays. And there were two sets of patients, who had roughly the same symptoms (head pains and bleeding), but one wasn't treated because the X-ray test showed that their problem wasn't a fractured skull. Would I say that the X-ray test is broken? Of course not.
Nicely done, thank you! My brain is broken, and this "informal reasoning" is harder than it looks. In your case, the X-ray test is doing its job perfectly. And if the posited type 2 hypothyroidism needs different treatment from the type 1 version, which it probably would, then the TSH test will be a great way to tell them apart. What I don't think you're allowed to do is say 'no problem, can't be anything to do with your car crash' when what you mean is 'your skull is not fractured'. So the TSH test is a great test for TSH, and probably a good test for circulating thyroid hormones (although it doesn't give the whole picture). But I don't think that means that the TSH test is a good test for 'no thyroid hormone-related problem'. Do we still disagree? Can I phrase my A&B&C=>(D OR E) thing better? Or do I need to abandon it? Perhaps: Hypothyroidism (by which I mean any failure of thryoid hormones to act on cells).....
That example only works because fractures are involved in a subset of car crashes and car crashes are involved in a subset of fractures; either one can happen without the other. If that relation doesn't hold true, you would be allowed to say that. For instance, saying "no problem, can't be anything to do with your car crash' when what you mean is 'you weren't anywhere near a car at the time of the crash'.
Agree again, thanks
Well, what's the test for speed of metabolism? Usually it's measured by the consumption of oxygen (VO2, high-level athletes do that a lot) and that's not a particularly expensive or difficult test. I am sure there is data on the distribution of VO2 in normal population. Do you think this test would be adequate for your purposes?
I think it most definitely would. Broda Barnes didn't like it, but only because the test is stressful and so tends to give false negatives (you're looking for the resting rate). But as long as it's done carefully, it should be fine.
The resting VO2 will need to be post-processed to be a diagnostic indicator. A brief look indicates that it is a function of sex (higher in men), age (higher in younger people), and weight. Might be a function of physical fitness (or at least lean body mass) as well.
Yes, sorry, thank you. The important quantity would be metabolic rate divided by the best prediction from the known relevant variables, as you say. It was once a test for hypothyroidism, so whatever the last word pre-blood test was should be good enough. As I say, Broda Barnes found this test wanting and preferred waking axillary temperature (for females, on the correct days; for males, anytime), but it should be plenty good enough to establish that there's something funny going on. The problem is to draw the attention of medical science to it at all. I trust them to sort out the details.
You are digging into this problem and I suspect there's enough published data on RMR (resting metabolic rate) in healthy and not-so-healthy people to collate some interesting evidence.
Agree, we should be able to refute it or strongly support it from the published literature. My initial attempts at that look like refutation. How can fibromyalgia in Turkish women be associated with HIGHER body temperature if my hypotheses are true? And I wonder if there are enough Less Wrong readers with friends with these diseases to make a survey of some sort?
That's not how you find patients a lot of patients. It makes more sense to seek online communitites where people with the illnesses congregate. There's the patientslikeme forum: https://www.patientslikeme.com/forum/fibromyalgia/topics http://www.fibromyalgiaforums.org/ http://www.healingwell.com/community/?f=24
Oh, and I predict that the resting VO2 would be normally distributed, but with a skew towards low values, and the size of that skew should be directly related to the size of the problem. And that low VO2 should correlate strongly with cholesterol, fatigue, blah, blah, blah. And I've got no idea whether that's true. It's a prediction.
Well... Technically speaking, that's impossible because normal distribution is defined on the negative infinity to positive infinity range. So there should be some kind of a bounded bell-shaped distribution, might be a truncated normal but I have no idea whether to expect heavy or light tails. A paper reports that for the sample size of 535 people they have the mean of 241 ml/min with the standard deviation of 56.6. They have some graphs and eyeballing them the observed minimum is around 100 and the observed maximum is about 450 -- that indicates a bit of a right-hand skew. But their population is not normal, their sample is basically cardiac patients. You can go chase the references in that paper. At least one90543-6/fulltext) looks promising.
He's a busy man and you're very enthusiastic -- you have a personal stake and endocrinology is your third-favourite hobby :-/
Not only is it the sort of thing I've been looking for, I've linked it at SlateStarCodex. However, looking at the lack of response, I think want this sort of well thought-out material, I also want well-thought out material which leads to good conversation. This may be a harder thing to define.
I am flattered again. Why have you been looking for this sort of material, and how do you define 'this sort'? I will be happy to optimise for good-conversation-provoking-ness. I am seeking argument. I want people to tell me what I have missed.
Extrapolating from a sample of Myself, I think maybe people don't feel qualified to comment but think this is interesting, and well written, and are just upvoting and then waiting for somebody qualified to show up.
Agreed, but that doesn't explain why the second post of three sits at three votes.
No, I don't get that either. People liked the question, but didn't care about my attempt to answer it? I was really excited. Imagine my horror to find that there's a book called 'type 2 hypothyroidism', by a homeopath, which is full of the most ghastly pseudoscience, in spite of which a lot of the author's clinical observations are in fact my own predictions. Two months ago I would have thrown it away unread. Still, no one can now tell me that I'm making a horribly technical argument that no one can understand!
As I recall, homeopaths do extensive interviews of their patients-- this might give homeopaths a chance to notice true things, even if their treatments are nonsense.
Oh, absolutely agree. For years I've had my back sorted out every six months or so by a local chiropractor, and I know that the actual beliefs of her profession are lunacy, but she seems to me to be a really skilled physiotherapist who is extremely good at getting rid of my back pain. And she's really nice. I've tried things like booking appointments three months in advance to control for regression to the mean, and all I can think is that either what she does works or I'm buying a really good placebo which works whether I believe in it or not. It's more that I'm a bit annoyed to have come up with a nice theory, which at the time I thought was really clever, and then found it already published, along with a plausible-looking mechanism in 'Medical Hypotheses', of all places (how my friends laughed), and then found an actual book about it by a man who clearly doesn't have an enormously powerful filter for loony ideas.
Spinal manipulation (of the kind practiced by chiropractors) has been shown to be an effective treatment for acute back pain...
Oh brilliant! Well done medicine! How long have they been claiming that? For twenty years I've been going to see a witch-doctor, and now it turns out her spells really have kept me out of a wheelchair. ---------------------------------------- Aargh, I've just believed you without checking because it fits. A primary sin. Do you have a reference for that?
Never mind. My original source was my father (who's usually pretty reliable when it comes to pseudoscience) but apparently the current Cochrane review says it's no better than placebo. (The subluxation theory of chiropractic is nonsense, but it's not ridiculous that fiddling with someone's back can relieve back pain - massages, for example, tend to feel good.) (http://www.ncbi.nlm.nih.gov/m/pubmed/23169072/?i=3&from=/22972127/related)
The thing you linked is not from Cochrane. They say: http://www.cochrane.org/CD005427/BACK_combined-chiropractic-interventions-for-low-back-pain I paraphrase: (it works, a bit, it's as good as anything else as far as we know, we have no clue really, further research is needed.) That looks like science. I am glad they do what they do.
Your dad might be right! This is from NICE (British recommendations for national treatment, a very sane system in my opinion, they try not to waste public money on things that don't work or are too expensive) I have found over the years that a single session every year or so obliterates a problem that, if left unmessed-with becomes painful and eventually restricts my ability to play various sports. The first time it was done (I was about 25?), a short-sighted friend blanked me in the street because the way I walked had changed and she didn't recognise me. She said the way I walked had been very characteristic, and now it was more normal! I don't know what NICE are basing their recommendation on, they could conceivably be going after a cheap placebo effect. ---------------------------------------- P.S. My nice chiropractor says I have: Ilio-psoas hypertonicity secondary to Sacro-Iliac instability. P.P.S. Careful. Chiropractors are loonies. Their explanatory theory is rubbish. My personal chiropractor is great. I would be very very suspicious of even her colleagues, let alone the rest of her profession. On the other hand, at least they are trying obvious things, to see if they work.
I am pathetically grateful for your flattery, but really! I came here for an argument...

The Institute of Medicine in the US last year recognized CFS as systemic exertion intolerance disease (SEID). Does their process tell us something new?

Thanks! I don't see anything new there, but I'm interested in the inclusion of 'orthostatic intolerance', as it's a hypothyroid symptom which I don't remember previously seeing on conventional CFS symptom lists. The alternative types all seem to blame 'adrenal fatigue' for it. I think they think the adrenal glands wear out from over-use. From my point of view there could either be underactivity of the adrenal glands directly caused by hypothyroidism (it wrecks everything), or 'peripheral resistance to adrenal hormones' caused by whatever is causing the thyroid resistance / insulin resistance. It certainly tallies with my experience. I found for years that I'd feel dizzy if i stood up quickly, sometimes to the point of nearly fainting. It was put down to low blood pressure, so it was a bit of a surprise when I found that my blood pressure had gone slightly high but it was still happening. All fixed now.

If this is true, then the most likely world I see in which it gets accepted is one where T3 tests become more like glucose tests: reasonably cheap, and available for patients to self-administer at home.

No, the T3 test is well known. We only have to have a very little faith in medical science to think that the only way these things can be occult hypothyroidism is if they don't show up on any usual thyroid hormone test. And for all my recent ranting, these are good, clever people, trying their best. The problem must be hard.

in order that someone with real expertise in this area takes this idea seriously enough to have a go at refuting it?

What would it look like if someone did take the idea seriously? What do you want to happen?

EITHER (2.1) CFS/FMS/Hypothyroidism are extremely similar diseases which are nevertheless differently caused. OR (2.2) The blood test is failing to detect many cases of Hypothyroidism.

I don't think 2.1 and 2.2 are mutually exclusive. Both could be true.

Agreed, thank you. I guess I should drop the word 'either'? But then it doesn't read quite right as english, even though it's better logically. Anyway, in that case we'd have some 'genuine' CFS and some 'type 2 endocrine mistaken for CFS'. And of course there'll probably be a few 'type 1 hypothyroidism carelessly mistaken for CFS' in there as well.
Well the first step would be to take a CFS/FMS population and see if many of them have low basal metabolic rates and low peripheral body temperatures. If that's not true, then game over. It's hard to imagine hypothyroidism without slow basal metabolism. After that we should try treating those people with desiccated thyroid, since that's what all the alternative types claim works. We should try carefully increasing the doses until we get some sort of reaction, and try to find the balance point where you're treated but not over-treated, which will probably be different for different people. I'd anticipate that doing a lot of good for at least some of them. After that we could play around with T4/T3 combinations in various proportions, trying to find an optimal treatment, and working out what the various mechanisms are, and if there's something in NDT that makes it superior to the synthetics. It may be worse. Once we had an idea of what sort of things work and on how many people, we could have a pop at a formal treatment protocol, and then I don't see why that couldn't be done double-blind, randomised, placebo-controlled. All those things are important when you're trying to prove something works. But I think all of them probably get in the way when you're trying to elucidate mechanisms. I think what I'm getting at is that alternative medicine has had a pop at the first bit, and gone a bit of the way down the road of finding out what's going on, whereas medical science has decided a priori what works and what doesn't, not checked particularly carefully, and then refused afterwards to accept any evidence except PCRTs as having any value at all. And in fact they seem to have mercilessly persecuted anyone who didn't follow their central guidelines. Which seems really weird, unless they trust doctors much less than I do. I'm advocating a sort of combination approach. Which I'd call: 'The Scientific Method'.
Thanks for more details. Yay for the Scientific Method. So, is your goal to find an individual researcher and some doctors to start a study, or a few studies, along the lines you have described here? If you want to make it happen, you may need to get together some money to fund that. Or it's possible you could take some time to find the people who would be interested and capable and talk them into doing it and find some other people with money and talk them into funding it. Or is your goal to change in general how medicine and medical research is done? The problems you describe here are widespread, and apply to more than this particular issue. Changing the approach of the entire medical community is a bigger goal than finding a few people who will take this particular idea farther. However, I think the reasons that people have not already done this research have a lot to do with systemic problems with no quick easy fix. I don't think it's just going to happen on its own. It's not enough to say to a receptive doctor or medical researcher "Hey, here is this promising idea, let's investigate it" and things fall into place. That's not how the systems work. If you want to make this happen, it's going to take a lot of work and a lot of time and likely a lot of money. Is that a project you want to take on? Not just, "Do you care about it a lot?", because you do, but are your life circumstances such that you can devote the time to taking this farther? There is very little research being done on CFS/FMS at all. And even less done on MCS (though that's another issue.) And very little on many other health problems. It's tragic.
Is MCS 'multiple chemical sensitivity syndrome'? I think that comes into the general bag of badgers, along with that thing where people get convinced they get headaches from the wireless. Break the TSH test, and all that should come for free.
So, my current goals are to: (a) sharpen this argument until I either believe it or not (I am dithering) Conditional on (a) being possible, and the 'multiple-hormone-peripheral-resistance-cochran-cause' thing looking solid: (b) make the idea widespread enough to get people capable of working out the details interested. (c) put such a rocket up 'medical science' that it will turn into a science (d) wipe frequentist statistics and the associated false inference techniques off the face of the planet (except as a discipline of pure mathematics, where they are as deeply and eternally true as everything else) You can tell that medical science isn't a science because it's got the word "science" in the name. We'll have to think of a new name for it. In Ancient Greek, obvs. and minor goals: (e) Nevertheless to save the reputations of RA Fisher and Archie Cochrane, great heroes of philosophy both. (f) Establish the reputations of Barnes and Lowe, serious geniuses who spent their lives on this. (g) Try to stop the blame falling on the people who introduced the TSH test. They were trying their best on a very hard problem. It is not their fault that their discipline was not strong enough to catch them when they fell.
You should believe (or not) a claim based on how well it matches empirical reality (aka "evidence"), not on how sharp the argument is. Sharpening is useful insofar it narrows down the range of relevant evidence, but it still does not replace it. Yeah, well... Misuse is not evidence of uselessness.
I'm not sure about this. I think this was always the problem I had with quantum mechanics at university. You can't catch them out, but they still don't make sense. That was what first drew me to less wrong, years ago. I mean, could many-worlds and copenhagen both be true at the same time? I think not, but I don't know why, and I think I'm making a claim that I don't understand, and which might be meaningless, and I don't know how to tell. At any rate, at the moment, with this particular idea, I seem to be able to explain too much. So I'd like to add extra constraints, and see how complicated my ideas have to become to match what I know. Oh dear, is that what I sound like? It's hard to tell from the inside. The thing is, I think they've got a few interesting things to say, but it's so badly written that I literally can't be bothered to read it closely enough to find out. I think their argument needs sharpening. The post-modernist claim of 'I have nothing to say and wish to communicate this' seems both relevant and reversed. Some of the frequentist tricks have their place. But they do seem very prone to misuse.
Not quite, actually the opposite -- you expressed desire for medicine to become more like a science and my link showed you some reactions to this idea.
Yeah, and I should totally read the damned thing. Your enemies' arguments are the most important source of ideas. I need a microfascist to stand on my left shoulder and point a gun to my head.
I don't know about needing to read it. The relevant point is its existence, the details of arguments might be amusing but hardly informative. It's not a paper about medicine, it's a paper about fighting oppression.
And actually, if there's this widespread attitude in medicine that only PCRTs and long-held-expert-opinion matter, and every other form of evidence should be discounted in the name of science, then maybe what they conceive of as 'science' is acting oppressively. PCRTs rock for solidity, but they are hella blunt tool. long-held-expert-opinion also rocks, but it does not come from PCRTs! Anecdotes and clever ideas are tricky-as-all-hell, but that doesn't mean you should ignore them. I don't suppose you've read that wretched paper and can summarise it?
I've paged through the paper. Blah blah microfascism blah legitimacy of truth blah Cochrane hierarchy blah Jacques Derrida blah hegemonic discourses blah subjugated knowledge blah 20th century totalitarianism blah Orwell’s totalitarian vision blah we must resist the totalitarian program blah blah blah. Money quote: "Those who are wedded to the idea of ‘evidence’ in the health sciences maintain what is essentially a Newtonian, mechanistic world view: they tend to believe that reality is objective, which is to say that it exists, ‘out there’..."
They likely don't make a good case for their opposition to the focus of objectivity, but the focus on objectivity is not without problems. On example would be placebo-controlled drugs, in standard trials it doesn't matter whether people who they get a placebo or an active drug know what they are getting because that's subjective knowledge. The thing that matters is whether an objective third-party thinks the experiement tried to control for placebo. As far as microfascism goes, the law that's in effect that forbids me from healing other people was passed under Hitler.
Sense make not. Double-blind trials are double-blind for a reason. And subjective knowledge can certain affect objective outcomes, that's not an issue. ...and so what?
We know from Rabkin et al's paper How blind is blind? Assessment of patient and doctor medication guesses in a placebo-controlled trial of imipramine and phenelzine. that particpants in drug trials often know whether or not they get the active drug. Standard protocols for double-blinding don't effectively prevent the participants from knowing whether they get a placebo or the real drug. Yet there little interst of people running studies to ask the participants of their trials whether they know what they are getting.
OK, but how does that lead to "the focus on objectivity is not without problems"? Badly run trials are evidence for the proposition that some trials are badly run, not for the proposition that focusing on objective results is problematic.
It's not about badly run trials in the sense that trials are not run according to the gold standard. The issue is that taking active pills frequently feels different than taking sugar pills even when both pills look the same way. That's information that patients can use to know whether they are on the active drug. In a world where people would sincerely care about whether trials actually prevent the participants from knowing the questions that Rabkin's asks would be routine questions in every trial. Asking patients whether they think they got the drug or placebo, is querying for subjective knowledge. That's a "way of knowing" that yields knowledge but that's not practiced. A "way of knowing" that the paper you linked would predict to be neglected.
Thanks, maybe I'll save it until after I'm dead.

Low Body Temperature

It is a very strong prediction of this theory that low basal metabolic rates, and thus low basal peripheral temperatures will be found in many sufferers of Chronic Fatigue Syndrome and Fibromyalgia.

If this is not true, then the idea is refuted unambiguously.

After googling that claim that leads to Wilson's syndrome. Do you think Wilson's syndrome is what you are talking about?

And thirdly: I've also now read 'Your Thyroid and How to Keep It Healthy', by Barry Durrant-Peatfield, who appears to have been a proper doctor who had the disease and tried the obvious things and was converted. There are a couple of mistakes, to my mind, in the book, but it's basically sound from my point of view if taken as the honest report/advice of a brave man rather than as the whole truth. In fact given that he 'voluntarily erased himself from the medical register' and went into retirement, I'd be tempted to call him either a martyr or someone who didn't think he could back up his beliefs in star-chamber. You might well think him a quack who was damaging people. I now strongly suspect that he was failing in his professional duty to ignore the evidence of his own eyes, and to not do the things he thought helped. He does seem quite concerned about fluoride and mercury fillings. I haven't looked into those. Yet. Sigh. And he talks about adrenal problems a lot. I don't know what I think about that. Certainly I wouldn't be at all surprised to find out that it was possible to have a 'peripheral resistance to adrenal hormones'.
And I should also say: It sounds like the Wilson in question has taken a tradition of medicine that has existed since 1940, misunderstood it, and then named it after himself. One of the problems with trusting anyone in this mess is that medical types are in business to make a profit. I don't hold that against them, and it doesn't necessarily mean that they're not trying to help people, but it may in this case have led to a certain carelessness. I would not personally choose to trust my health to this man, but it is perhaps a measure of how desperate people are that some people have done. It doesn't seem that Wilson has added anything new, but at least according to Wiki, he was claiming that it's not hypothyroidism, it's caused by 'stress', which sounds like some weird compromise between Barnes/Lowe and conventional medicine's approach. The Wiki article says 'caused by low temperature', so definitely not what I'm claiming theoretically, that would be a symptom from my point of view. But they also accuse poor T4->T3 conversion, which would do the trick as well as Lowe's 'peripheral resistance', but which would show up on blood tests, unless they're talking about conversion inside the cells themselves, in which case err? I think T4->T3 conversion is generally believed to happen mainly in the liver, so failure of that would definitely show up on blood tests. In short, I think, assuming Wikipedia is correct and not just getting the wrong end of Wilson's stick, that: Wilson was trying to sell Barnes/Lowe's ideas to people. He has either misunderstood them or disagrees. He is however seeing exactly the polymorphous syndrome I predict, with the associated low temperature that Barnes thought was the best diagnostic for hypothyroidism, and he seems to think he can actually cure the problem with high doses of T3. Neither Barnes nor Lowe claimed that they could cure it, as far as I know, but it wouldn't surprise me if there were occasional spontaneous recoveries. Especi
This: https://en.wikipedia.org/wiki/Wilson%27s_temperature_syndrome Sounds like exactly what I'm talking about. He's observing as a problem what I'm claiming must be true. I'm surprised by this: "thorough review of the biomedical literature has found no scientific evidence supporting the existence of 'Wilson's Temperature Syndrome'." There's plenty of evidence that these problems exist, the argument is about what to call them, what causes them, and how to treat them. I wonder if they mean that there's no evidence that Wilson's patients have low body temperature. If what they mean is: "There's good evidence that Wilson's patients had basal peripheral body temperatures around 98.6/37C before he treated them", then I'm surprised and possibly refuted at the same time. I don't see how my idea can be true and yet he's avoiding picking up at least some cases of what I'm talking about, and I do strongly expect low basal peripheral body temperatures in those people. If that's not true, then my/Barnes/Lowe's idea is wrong.
The basic diagnosis for Wilson's Temperature Syndrome as described on http://www.wilsonssyndrome.com/ seems to be CFS symptoms + normal hormonal tests + lower temperature. They say:
Oh cool, thanks! Then he's talking about exactly the thing I'm talking about, and he has a different idea about what the mechanism is, and I don't like the sound of his treatment. I shall investigate. I wonder what he thinks causes the low body temperature in the first place? Thanks for the link! Have you happened upon a strong rebuttal of his claims, perchance? And do you know if he happened upon the idea independently, or whether he's an intellectual descendant of Barnes and Lowe? Hundreds of doctors has to be a lie, hasn't it?
They provide a list of Medical Providers for Wilson’s Temperature Syndrome that gives the addresses of doctors that supposedly follow their protocol. If you think it's a lie, then you could count the number of doctors in their list and contact a few of them as a sample. At the moment I don't know much more than what's written on the website.
Here's another one I did look at ages ago: http://t3doc.com/ I may be suffering from some sort of cross-cultural confusion, but Dr Morris's website appears to exist solely to make him look like an irresponsible lunatic who has been handing out powerful hormones for weight loss, of all things. Especially since I think that this has been tried many times and found wanting. On the other hand, my faith in medical science is perhaps not now as strong as once it was, and if he's really an Ivy-League non-conformist, maybe he noticed the problem a long time ago. What I liked about it was that he has apparently noticed that in doing this, he was accidentally curing Chronic Fatigue. Again, no idea whether what he's doing actually works, or what sort of terrible side-effects it might cause, or anything. But again, it looks far too obvious to be the right answer. Does anyone know if there's one of these maniacs in England? If I can find a semi-trustworthy source of T3/T4 I am tempted to experiment on myself to see if they work as well as desiccated thyroid. I'm a bit nervous of NDT myself since it's probably an allergen, hypothyroids are prone to allergies, and I wouldn't be terribly surprised if I caused one of the well-known thyroiditises by taking it. One strong objection to Dr Morris' idea is that if it's T4->T3 conversion, then there so is a blood test to detect it. On the other hand, if he hasn't been doing the blood tests, then he won't have noticed that. And I now think I can explain what's really going on. When I first looked at his website, I didn't have the type 2 idea. It seemed like a minor detail of Lowe's work, and I was focused on working out what was wrong with the tests.
OK, a brief look around Wilson's site gives me: He is claiming independent invention, and he never once mentions Barnes or Lowe. I didn't see any obvious pseudoscience. (no crystals, no magic electricity thought reading machines) He doesn't seem to have any obvious explanatory theory. What I've read of what he has to say makes considerable sense to me in the light of the above. He doesn't seem to be claiming that there's been a PCRT of his protocol, without which I don't believe it works. He is absolutely claiming that the condition can be cured. Not alleviated. Cured. I think conventional medicine concluded that T3 monotherapy was a disaster when they tried it for thyroid problems. They're currently involved in a twenty year catfight about whether adding a bit of T3 to the usual T4 is a good idea. They've tentatively concluded no, but I think (and Lowe thought) that their reasoning is wrong. And Kenneth Blanchard, who's unconventional, but a proper endocrinologist, thinks it works a treat. On the other hand, I spotted a couple of mistakes in his book, so I don't trust him either. Has he (Wilson) published anything? If not, why not? It all looks a bit too good to be true, to me. And a bit too easy.... If it was this easy we should already know. On the other hand, how the hell did I miss this?
I found it by googling: Low Body Temperature chronic fatigue syndrom
Indeed, in fact I think I might have seen it before and ignored it. Very early on, when I was trying to work out what the hell was wrong with me, I read about 'adrenal fatigue', and thought it looked very plausible (amongst a very large number of other plausible possibilities), but Wiki said it wasn't a thing, and my doctor agreed, so I forgot about it. Maybe since then I've had filters on. There's even a chapter of Durrant-Peatfield's book, which I read cover to cover not three days ago, which mentions Wilson's Syndrome in exactly the sort of way that you'd expect an English non-conformist to mention a man who'd named someone else's ideas after himself. But maybe that's not true. Maybe Wilson really did come up with it on his own many years ago, before the internet would have enabled him to find Barnes or Lowe. Sure looks like it's going a bit nuclear now. And still endocrinology isn't interested? What on earth is going on?

MyBasis Peak measures skin temperature and sleeping data. Would you predict that you can distinguish people with CFS based on their MyBasis Peak data?

I once did some work for these people: http://www.temperatureconcepts.com/ And I know they're excellent and sincere, and if I was trying to get pregnant I'd certainly have one of their devices. I think it is deliberately designed to measure sleeping metabolic rate, because that tells you a lot about female cycles. They might already have the data! ---------------------------------------- Damn it, it turns out I emailed them about this in November, when I was first thinking about this. No reply. I forgot. I shall get hassling.
On the basis of this: http://www.mybasis.com/en-GB/technical-specifications/ Hell yes! If it does what they're claiming, and does it accurately (let us say 0.1C for skin and ambient temperature), it should give you a great proxy for sleeping metabolic rate, as well as all sorts of other data about how you sleep, which is probably going to be affected in all sorts of ways. I'd imagine not-too-much machine learning applied to this data should fairly cleanly separate hypometabolic and normal persons. I would expect it to pick up all sufferers rather than just CFS, as well as people on diets and people with slowed metabolism for other reasons, but apart from starvation I don't know of many things that will slow the resting metabolism. And it might fail to pick up people with fevers. But if it's built with accurate bits, and can record the data as time series we can examine, then if that doesn't make a good test for hypometabolism, I'll give up and probably never think about this again.
It's probably relatively easy to get a dataset of a few healthy people as a control. Recruiting people with CFS would be more effort but still in the realm of what's possible with realistic effort. If you think your illnesses has a lot to do with temperature regulation it might be valuable for you get a MyBasis Peak yourself. With 129€ the cost isn't prohibitive.
I'll consider it, definitely. At the moment I have my trusty thermometers, and they have proved reliable guides. But it is actually quite tricky to take a reliable temperature, especially with the modern digital things (ironically because they are so speedy and sensitive). I had to practise lots, so I can quite see how they fool people. I think the old mercury ones were a bit of a pain, but on the other hand, they force you to do it right, and it's much less easy to bugger up armpit temperature than mouth temperature, which is why Barnes was keen. In his book he speculates that the reason that all the other doctors hate the idea is that they can't charge patients for taking their own readings! He really did think it was much better than anything else.
It's especially tricky to take a temperature with a thermometer while you sleep . There's certainly economic pressure for a doctor to order a blood test and the test getting written into standard care guidelines but not for costant self-measurement of temperature.


Found this for "Wilson's syndrome", but can only see the abstract:


It looks like it might be supportive, but it also looks crap. No mention of blinding, randomising, or placebo in the abstract.

Can anyone see the actual paper and link to it here? And can anyone work out whether these guys are allies of Wilson, or trying to break him? Because that matters.

This, on the other hand:


Looks solid, and looks like refutation. They claim no... (read more)