Papers questioning TSH as a diagnostic keep coming - Thyroid UK

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Papers questioning TSH as a diagnostic keep coming

diogenes profile image

A new Australian paper which examines the value of TSH testing and its relationship to best hypothyroidism detection. Don't agree with all of it, but the concept that FT4/3 measurements are better than TSH is well covered.

Endocrine

doi.org/10.1007/s12020-021-...

Thyroid testing paradigm switch from thyrotropin to thyroid hormones—Future directions and opportunities in clinical medicine and research

Stephen P. Fitzgerald, Nigel G. Bean, James V. Hennessey, Henrik Falhammar

28 Replies

Thanks for the link.

Thank you, once more!

Ooh .. they 've acknowledged you (&Co) exist ....and not just once, but thrice :)

That's good .

Shame they haven't quite understood your point yet , but it's another step in (sort of ) the right direction ..

I hope no one takes them up on using 'fT4 alone' for diagnosis though, after all TSH does have some uses. and throwing it out all together would probably mean lots of folk waiting a lot longer for treatment to begin, and they'd be in a worse state by the time it did.

Oh dear. On and on it went and absolutely no mention of the different problems of patients with no thyroid. Or did I miss it?

After Thyroidectomy my health went slowly downhill over six years, until I realised the famous “little white pill” of T4 was hopeless on its own. I begged my GP for a full blood test of T4, T3 and TSH. It showed T4 was well over range and T3 was well under range but TSH somehow seemed fine. I clearly was not converting T4 to T3 but only a blood test of each would flag this up. If they had not done T3 test, they would have reduced my T4 and I would have suffered even more. So why the new idea to test T4 alone instead of TSH? When will they realize we need all three tests to know what is happening in someone’s body? I despair.

diogenes profile image
diogenes in reply to Hennerton

It's a start, if TSH use is downgraded. Recommending the use of FT3 will make a lot of doctors red-faced, so I'm not expecting that progress yet. The field hasn't yet cottoned on to the role of the thyroid directly producing T3, under the influence of TSH.

Hennerton profile image
Hennerton in reply to diogenes

It is not much of a start, because as I explained, I was only on Levothyroxine when my blood test showed what a mess I was in. If I had not persuaded my GP to do it, they would have been horrified by an over range T4 and would immediately have reduced it. I would still have had an under the reference range T3 and yet my TSH would have looked better at the next blood test and no one would be able to explain to me why I felt so unwell. Only testing all three is good enough. That is what we should be fighting for, along with T3 on prescription and no quibbling.

Tythrop profile image
Tythrop in reply to Hennerton

How did you feel when tjey eventually gave you T3?

Hennerton profile image
Hennerton in reply to Tythrop

It took some working out to find the right dose but the effect was immediate. Then I tried all kinds of variations of T4/3 before settling on what I currently take. I am fortunate that my GP still prescribes it and allows me to do as I please. She says I know more than she does about thyroid matters. Nevertheless, I am very cautious about over medicating, as I am horribly thin and I find T3 very powerful.

Zephyrbear profile image
Zephyrbear in reply to Hennerton

Thankfully, totally ditto here... my GP has given up on trying to argue with me, as has the endo, and I can still get my T3 on the NHS. The only place where I differ from you is that I am not, by any stretch of the imagination, thin... very or otherwise.

Tythrop profile image
Tythrop in reply to Hennerton

This is most intetesting and I like the bit about the immediate effect! It is particularly intetesting as I have just gone back down to 1.5 grains of Armour NDT. I went up to 2 with a bit of trepidation but it felt that the hypo symptoms came back (weird I know given that was an increase). Anyway I can always go back up again and this wad all against the background of a bereavement so I didnt want any more aggro.

Thank you for this, so encouraging!I am sure you have all seen it, but another paper cited in this one gives the evidence that T4 and T3 levels are a better diagnostic parameter than TSH and they comment that this may be true for treatment monitoring too.

liebertpub.com/doi/10.1089/...

A big subject but I'd like to make one elementary comment.

In healthy people TSH and fT4 tend to be linked and exits their reference intervals around the same time as can be seen in Figure 1 of this paper eje.bioscientifica.com/view... . We would tend to expect this because they are 95% reference intervals, so each parameter will have exactly the same proportion of subjects outside its refence interval. i.e. 2.5% below and 2.5% above.

However, if the thyroid is damaged the pituitary will have to work harder to flog the thyroid into producing more hormone, i.e. TSH will be higher. Thus, TSH is an excellent marker for primary hypothyroidism. Furthermore TSH is also excellent at spotting early thyroid failure that may go onto clinical hypothyroidism. Also, in cases of mild thyroid failure which the patient may not noticed there are adverse consequences such as high cholesterol which can be caught early.

Given the above we would expect an excellent correlation between TSH and hypothyroid signs and symptoms. This doesn't happen, there is a feeble correlation. In part this can be explained by there being many isoforms of TSH with varying bioactivity. The TSH assay counts apples, pears, grapes, rasberries, bananas etc. and assigns equal weight to them all.

Another issue is that TSH is driven by TRH and the response of TRH receptors in the pituitary. Insufficient stimulation by TRH will hold TSH down.

Now we can do some crude and elimentary arithmetic (not actual calculations). If thyroid hormone feedback to the pituitary was the dominant factor we would see a clear positive correlation between hypothyroid signs and symptoms and TSH. On the other hand if TRH stimulation was the dominant factor controlling TSH we would see a clear negative correlation bewteen hypothyroid signs and symptoms and TSH (as TSH gets lower there would be more symptoms). However, there is very little correlation between symptoms and TSH. This suggests that there is a roughly equal amount of hypothyrodism caused by thyroid failure and insufficient TSH stimulation. Contrary to current opinion the numbers suggest that the prevalence of central hypothyroidism is of a similar order to that of primary hypothyroidism. This does not imply pituitary damage, rather underperformance which can have many causes.

We should appreciate the power of TSH to spot early thyroid failure but accept that it is of limited use for detecting other forms of hypothyrodism, these other forms seem to be as common as primary hypothyroidism.

diogenes profile image
diogenes in reply to jimh111

We are in the midst of writing up a description of the complete hypothalamus-pituitary-thyroid-corporeal control of thyroid function. At base it is easier than we thought in that it can be fully described by putting together a) hypothalamus TRH stimulating the pituitary ,( b and c) the pituitary TSH stimulating T4 and T3 production by the thyroid (NB if the thyroid is failing in T4 production (b), the TSH is uprated to promote and maintain T3 production (c) there by a feedforward control) , d) the conversion of T4 to T3 in the tissues via the bloodstream and e) the effect of T3 and T4 on stimulating the hypothalamus. Each equation describing one part is basic - the difficulty is combining all together in a coherent whole. A computer algorithm is essential here. So far we propose that the hypothalamus is preferentially controlled by T4, but if T4 is low or absent, T3 will take its place. For the pituitary, T4 and T3 stimulation are similar. The whole solution is aimed at maintaining as constant a FT3 level as possible and one suitably able to both respond rapidly to changed conditions, but equally be robust in more stable situations. The maths is finished, but we need to write up in a coherent way, without confusing people - this is not so easy but we are getting there.

tattybogle profile image
tattybogle in reply to diogenes

are you writing for endocrinologists ? Ladybird did a good series you could use for a template.

"HOW IT WORKS"

'THE THYROID'

"This is John ....

These are John's friends .....

They can see something you haven't .....

Can you find it ?.... "

jimh111 profile image
jimh111 in reply to diogenes

That's quite a challenge and will negate current dogma.

T4 regulating the hypothalamus has even more profoud effects because TRH regulates TSH bioactivity. I can't remember the papers where I read this but this is the original research pubmed.ncbi.nlm.nih.gov/308... , the full paper is available on Sci Hub. I haven't read the study I've cited! There are follow up studies that confirm this but they don't come to mind.

A further issue is that as you noted TSH regulates T4 to T3 conversion in tissues and presumably this includes the regulation of local T3 levels in organs such as the brain.

Thanks for doing this research, it is so much more difficult than the standard studies but also more useful.

jgelliss profile image
jgelliss in reply to diogenes

Wow!!! That is so very interesting. I can hardly wait for the kut come of the report Diogenes. I think it will be extremely helpful and can answer many questions as to why some of us do better with different thyroid hormones more T4 less or no T3 or in reverse .Thank you in advance for all your hard work time and efforts to help ease many of our lives.

Tythrop profile image
Tythrop in reply to jimh111

Folowing this I ask :Could it possibly be that, following a big episode of postpartum hyperth/Graves/autoimmune thyroiditis (whereby patient bevomes very poorley but the cause of symptoms only picked-up late by GP ie. late identification and trestment of extremely high t4etc and vey supressed tsh) could then the tsh production become permanently downregulated by pituatory or Hypothalamus.? Thereby preventing it "signalling to GPs" a later development OF hypothyroidism /hashimoto. (low tsh+ low t4+ low t3) so medics refuse treatment as tsh is not high... It will never be high because it cant be now?? Is this a scenario that could exist?

jimh111 profile image
jimh111 in reply to Tythrop

Absolutely the axis can become down-regulated, it may or may not recover in time. Doctors never recognise this, the research is there but they don’t put two and two together.

Another point, my own thinking. Graves’ antibodies imitate TSH and so stimulate the thyroid and T4 to T3 conversion. These antibodies hang around for about a year or so after a thyroidectomy, once they have gone the patient will lose the beneficial effect on T4 to T3 conversion. This matters if their axis is down-regulated and their TSH is insufficient.

Tythrop profile image
Tythrop in reply to jimh111

This is SO reassuring. I was medicated with Carbimozol /propythyrurcell and then t4 once a day and t3 thrice a day.post natal thyroiditis. Very very ill and causing post natal depression. LIVING HELL. As a new mum at 40. My "system righted itself". No opps. But was told that I would probably get Hashi/hypo sometime in future. But 15 years on when symptoms appeared I was tested by NHS and refused meds as tsh low but in range, t4 just below and t3 lowish in range. So for years ive had tests and symptoms but no meds. I found I has anti tpo antibodies by private test. NHS didnt do this at all. All the time all 3 tsh, t4, t3 bumping along the bottom for 10+ years. I gave up on nhs and started Armour ndt about 18months ago. I HATE doing it alone but no option.

jimh111 profile image
jimh111 in reply to Tythrop

I see so many similar cases on the forum. I kept a log of these but stopped when I got to 70 cases. When this happens you need abnormal T3 / T4 ratio to compensate for the loss of conversion within cells, loss of local T3.

Tythrop profile image
Tythrop in reply to jimh111

Thankyou for taking an interest.I dont exactly understand what this means in Micky Mouse terms, but I hope the Armour (t4+t3) will do the job as I cant get t3 from NHS. Im not sure that I'm feeling "right" but I know you haven't got time etc to treat us all.

jimh111 profile image
jimh111 in reply to Tythrop

Endocrinilogists assert that if we take T3 we should aim to restore normal serum T3, T4 levels. However, much T4 to T3 conversion takes place within organs such as the brain and these organs maintain higher T3 levels than in the blood. If conversion is impaired it is likely we will need higher than average blood T3 levels to compensate for the loss of T3 in these organs, loss of the T3 than they convert from T4. This is not desirable because higher blood T3 levels may be too much for other organs, but we have no choice.

Armour might well help. If it does I would aim to stay on the lowest dose that makes you well.

Tythrop profile image
Tythrop in reply to jimh111

Thankyou

How many papers does it take to change an endocrinologist’s mind?

helvella profile image
helvellaAdministrator in reply to penny

I have often wondered whether it will take the serving of court papers.

We have seen the courts needing to get involved in medical practice all too many times.

Regarding thyroid, I suspect the only reason that there haven't been major cases is the sheer difficulty of getting a case to court - and funding it. Doing so takes an enormous effort by the complainant and many would be unwilling or unable to do what is needed even if they could afford it.

diogenes profile image
diogenes in reply to penny

An infinite number, until the accepted great and good do the appropriate work and claim the credit for themselves. Science is like all fields: the self-appointed leaders won't accept anything from elsewhere until they have repeated the work and started the proclamation of the new stratagem with self-advertisement. Only then will it slowly filter down to the GP baseline. Can't have outsiders telling them what has been been wrong for more than 30 years. How else can one interpret the parroted statement - there is insufficient evidence! By whose standards and by whose authority? And by whom and from whose work will acceptance of change be finally accepted? I leave you to answer that. I'm not answering that, though I know the outcome.

Tythrop profile image
Tythrop in reply to diogenes

This is reminicient of the recent case of the Post Office.

I was thinking of ‘how may psychiatrists does it take to change a light bulb? Your answers sum up the situation.

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