The Thyroid Madness : Core Argument, Evidence, Probabilities and Predictions

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 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 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://​​psyched­u­ca­​​

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.