Thyroid hormones are better diagnostics than TSH - Thyroid UK

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Thyroid hormones are better diagnostics than TSH

diogenes profile image
15 Replies

This letter from us has been published in the journal Thyroid. It defends a paper by others who have shown by a large study that FT4 is better than TSH in diagnostic utility. Unfortunately FT3 wasn't done, but at least the focus has moved away from TSH.

Thyroid

DOI: 10.1089/thy.2020.0627

1

Thyroid

Response to “Clinical parameters are more likely to be associated with thyroid hormone levels than with thyrotropin levels: A systematic review and meta-analysis” (DOI: 10.1089/thy.2020.0627)

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Letter to the Editor

Re: “Clinical parameters are more likely to be associated with thyroid hormone levels than with thyrotropin levels: A systematic review and meta-analysis” by Fitzgerald et al. Thyroid. 2020 doi:10.1089/thy.2020.0466

Rudolf Hoermann MD, John E M Midgley PhD, Rolf Larisch MD and Johannes W Dietrich MD.

15 Replies
helvella profile image
helvellaAdministrator

This links straight to the description of this response:

liebertpub.com/doi/abs/10.1...

Unfortunately, paywall prevents access. :-(

Ironic - as the original article is available:

liebertpub.com/doi/10.1089/...

diogenes profile image
diogenes in reply to helvella

OK, so I'll mail direct to Louise.

helvella profile image
helvellaAdministrator in reply to diogenes

Thank you.

helvella profile image
helvellaAdministrator in reply to diogenes

Do you have access to the other two responses they appear to have published?

diogenes profile image
diogenes in reply to helvella

Yes, but they have rejected the idea of a unique "set point" for describing health, which we don't agree with. It's all a bit mathematical and doesn't illuminate much.

london81 profile image
london81

thanks for this. i’m in the middle of ‘debating’ the unnecessary reliance on tsh with my fathers endo, after i helped him start on NDT. He’s just had another set of blood test and i know his tsh will still be suppressed because of the T3. I have put together a letter to the endo, which includes a photo of my dad pre and post NDT looking much better, as well as descriptions of his improvements. I also have a letter from a consultant endo written about me which says when on ndt/t3 tsh is suppressed. I intend to send these asap. I read the study you linked and I think it will help, am I reading it correctly?

thank you

haggisplant profile image
haggisplant

It makes sense as t4 has a half life of 7-10 days. Tsh varies during the day or week or month.

DippyDame profile image
DippyDame

Why do medics side line the importance of FT3?

Does it lead to answers they don't want to acknowledge?

....and more difficult questions!

Makes no sense!

diogenes profile image
diogenes in reply to DippyDame

They do it because they make an unconcious mistake. That is, if you categorise patients as being in a particular state, whatever their FT4 number is, you then unconciously say the same about FT3. It's a case of if there are 5 apples, there must be 5 pears. However, if you take a group of euthyroid patients, by the above argument, and make a graph of FT4 v FT3 you'd expect a straight line with high confidence between them. What you get is almost raandom noise. The docs seemingly are unable to link what that says with what only doing FT4 leaves out.

Valarian profile image
Valarian in reply to diogenes

... and yet, those same endos do (usually) routinely monitor TSH, FT4 and FT3 in hyperthyroid patients. They know that FT3 may remain high, even if FT4 is within range (and TSH non-existent) and that in the event of a Graves’ relapse, FT3 may become elevated before FT4.

They have learnt that in the bakery, having five doughnuts does not mean you have five loaves of bread, but do not apparently consider applying the same lesson in your greengrocers’ next door.

Curious.

DippyDame profile image
DippyDame

Comes as no surprise!

Heads buried deeply in the sands of time.

If they don't look they won't find - despite the fact that the proof is staring them in the face.

Meanwhile thyroid patients are suffering.

It's only thanks to the experts on this forum that I was able to find the clues that medics missed for decades......

Huge thanks to all

DD

jimh111 profile image
jimh111

Thanks for your letter challenging the use of TSH for diagnosis of hypothyroidism and your point about TSH being valuable for diagnosing (primary) hypothyroidism but it becomes of little value when approaching or within its reference interval. This is not surprising as TSH varies both during the day and (to a larger extent) during the menstrual cycle.

TSH (quantity and quality) is controlled by TRH as well as fT3 and fT4. How hard you push the accelerator pedal controls the speed of the car, even if the engine is a little out of tune.

I dislike meta-analyses. The outcome invariably depends on how the data is selected and ranked. During my training in computing we had GIGO (garbage in, garbage out) hammered into us, don’t over-analyse weak data.

Invariably hypothyroidism is defined in terms of TSH and fT4. We are then told that hypothyroidism cannot be diagnosed by signs and symptoms because they do not correlate with TSH. This isn’t just a case of putting the cart before the horse or even incompetence, it is fraud. This belief in TSH is a religion rather than science pubmed.ncbi.nlm.nih.gov/210... .

The claim that TSH is a sensitive marker is absurd. Only 2.5% of the population will have an elevated TSH or low fT4, as defined by the 95% reference interval. Also, TSH and fT4 tend to exit their reference intervals at same time as can be seen in Figure 1 eje.bioscientifica.com/view... . (If they didn’t there wouldn’t be an inverse relationship between TSH and fT4). A considerable number of hypothyroid patients have a normal TSH. In statistical terminology TSH is not a sensitive marker.

The other factor is that the assays are not always reliable. TSH assays measure presence not activity and fT4 assays can be inaccurate. I don’t have an understanding of the science but Figure 2 eje.bioscientifica.com/view... shows me that the standard fT4 assay is imperfect.

In present company (Diogenes) I’m going to skate on thin melting ice. TSH is a group of isoforms with varying bioactivity. The more TRH stimulation the more bioactive the TSH isoforms are, and vice-versa. As I understand it TSH assays are calibrated using a representative mix of isoforms with an unwritten assumption that everyone will have TSH of similar potency. Usually as fT4 falls TSH increases in quantity and potency stimulating more thyroidal secretion and stimulating T4 to T3 conversion in the thyroid and in peripheral tissues. This is great, high TSH indicates primary hypothyroidism and the patient isn’t too bad because the increased deiodinase is protecting circulating and intracellular T3.

The problem arises when TSH does not adequately respond to falling fT4. These patients have normal levels of TSH but with reduced bioactivity. Their circulating and intracellular T3 levels are reduced. I’d love to see a study that compared signs and symptoms in patients with a normal TSH with those with an elevated TSH - both with moderately low fT4 (e.g. 10 – 14 pmol/L). Certainly, on this forum I see patients with normal TSH and marginal fT4 having severe signs and symptoms. Free T4 is a better marker than TSH but neither are particularly good.

diogenes profile image
diogenes in reply to jimh111

I agree with a lot of what you've written. Maintenance of suitable FT3, against changing (falling) T4 output by the thyroid gland, involves as we've now found, feedback/feedforward actions in both the pituitary-thyroid and the hypothalamus-pituitary system pairs. These tightly control glandular output, and the feedback only system of FT4 and FT3 back to both pituitary and hypothalamus constitutes the body's plain signal that more or less hormone is needed. FT3 has to be maintained at all costs, until thyroid gland loss is so great that the essential brick in the wall fails, bringing down the rest of the wall. TSH has many roles, major and minor according to its isoforms eg in controlling bone homeostasis, We've just submitted a paper to J Theoretical Biology to explain the whole HPT axis control as we now understand it. This is lightyears away from the simple feedback only system at present believed. It promotes patient individuality in response to therapy, not blanket diagnosis, and implies that constant vigilance is needed through life to keep up with, and address suitably, thyroid hormone therapy.

jimh111 profile image
jimh111 in reply to diogenes

'We've just submitted a paper to J Theoretical Biology to explain the whole HPT axis control as we now understand it.'

I'm always impressed by your teams' drive and energy in producing so many detailed studies. I look forward to this new study - and will try and build up my energy and cognition for what will be a very challenging paper! This is not easy work, I admire those who undertake such difficult challenges. Thank-you.

humanbean profile image
humanbean

Your letter is available online here - no paywall :

sci-hub.tw/https://doi.org/...

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