How Does Thyroid Hormone Profile Differ on and Off Replacement Treatment?

[helvella]

A paper from a number of British medical/academic establishments including some names often mentioned here for their genuine interest in thyroid issues.

University of Manchester

Salford Royal Hospital

Cardiff University School of Medicine

University Hospitals Coventry and Warwickshire

Worcester College, Oxford

School of Medicine, Keele University

Res Consortium [ see resconsortium.com ]

The abstract, at least, is a very straightforward read.

How Does Thyroid Hormone Profile Differ on and Off Replacement Treatment?

Heald AH 1 , Premawardhana LD 2 , Taylor PN 2 , Baker A 3 , Chaudhury N 4 , Fryer AA 5 , Okosieme OE 2 , Dayan CM 2 , Stedman M 6

Author information

Clinical Endocrinology, 19 Dec 2024, 102(4):490-495

doi.org/10.1111/cen.15185 PMID: 39702980 PMCID: PMC11874186

Free full text in Europe PMC

Abstract

Introduction

There continues to be much discussion around optimisation of thyroid hormone status in hypothyroid individuals. We here looked the way that free T4(FT4) and thyroid-stimulating hormone (TSH) related to each other in a large laboratory sample of people who underwent a thyroid function test (TFT), split between those on levothyroxine replacement (monitoring test) and those who underwent a test to check for thyroid hormone imbalance (diagnostic test; not on levothyroxine).

Methods

TFT test (FT4/TSH) results were extracted from the Salford Royal Hospital Laboratory Information Management System during 2009-2012. This was a single site study. Requests includes a tick box for 'on levothyroxine' (yes or no). To minimise comorbidity effects, only samples taken in General Practices were used. For untreated patients only those who had single tests results were used; for treated patients, the median value across all their results was used. Cluster analysis considered an ellipse with centre on median values for log (TSH) and FT4 and the vertex based on 5% and 95% percentile values of both. The percentage of patients falling outside the ellipse boundary was considered for both treated and untreated populations.

Results

The total data set included 290,000 tests on 130,000 individuals. After filtering, FT4/TSH results were used from 12,006 (F 9231/M 2775; age < 60 5850/age ≥ 60 6567) treated patients with 43,846 test results. These were compared to the single results for 43,394 untreated patients (F 24,386/M19,008; age < 60 32,537/age ≥ 60 10,857). Cluster analysis showed for untreated patients, median values for TSH and FT4 were 1.8 mU/L and 15.5 pmol/L, respectively, with 24% of patient results falling outside the untreated 5%/95% percentiles. For treated patients, the median TSH was 2.3 mU/L (+30% vs. untreated) and FT4 was 18.9 pmol/L (+22% vs. untreated), with 22% of treated patients falling outside the treated 5%/95% percentiles. When considered against the untreated limits, 68% of treated results fell outside (split male 63%, female 70% and age < 60 67%, Age ≥ 60 64%).

Conclusion

The current treatment regimens of either low or high dose levothyroxine are not delivering the expected laboratory TFT profiles, with significant numbers of treated patients being well outside the expected values: both TSH and FT4 being significantly higher. This effect appears to be more prevalent in women than men.

Open access at EuropePMC:

europepmc.org/article/MED/3...

Or publisher's site:

onlinelibrary.wiley.com/doi...

[arTistapple]

This looks to me as if some serious statistics have been used here to prove that treatment/health is clearly not effectively measured by either TSH or even monitoring FT4. Also as you mention, serious people, serious about thyroid research involved, unlike that recent idiotic research from Newcastle. Heads should be hung in shame for those associated with that! Although I did not read the whole thing, only the conclusion, there was no mention of measuring T3. Hardly surprising since T3 is pretty much never measured. So much opportunity for research just cast away.

Am I thinking this is loud and clear or is my brain fog completely fooling me?

[helvella Administrator in reply to arTistapple]

Clearly this highlights issues which have been available for research since levothyroxine monotherapy was introduced. Though I fully accept that computer records, more test results, etc., all make it more feasible.

The issues of time of dosing, time of blood draws, and their relationship is also important.

And we have to be clear that many doctors will adjust the levothyroxine dose on scanty and inadequate evidence. Most especially all those who only get TSH tested will automatically have been excluded from this analysis.

[crabapple]

Glad they are asking the questions. However this has again reared its head:

"Another factor is that it is possible that some patients miss doses and then double or triple the dose prior having their TFTs checked thus resulting in a higher FT4 on the day while TSH remains slightly high in relation to the lag in TSH response to circulating thyroid hormone levels "

[helvella Administrator in reply to crabapple]

I agree.

I'm sure it can happen. But we need to know more about that. I am quite certain it does not happen with the levothyroxine-takers I actually know.

And if it does happen, they need to ask why? Do the individuals not understand? Or are they avoiding taking it for real reasons?

[crabapple in reply to helvella]

But even if it does happen, the numbers would have to be very high to affect any results. Otherwise it would just be hidden in the general noise surely.

[TSH110 in reply to crabapple]

The ever non-compliant patient eh? Who on earth does that with their levothyroxine? One in a million I’d say

[crabapple in reply to TSH110]

That and my comment above about nunbers are answered by cyberbarn below...

[tcpace in reply to crabapple]

Another factor is the possibility that they don't really understand what's going on so they have to blame the patients rather than try to rectify their own shortcomings.

[FallingInReverse]

What I wouldn’t do for the same study but including ft3…

[TSH110 in reply to FallingInReverse]

Oh yes its sorely needed but if these medical idiots won’t test it it makes it really difficult as the data is not being collected - its scandalous given it’s THE most important of all. What drives the whole thyroid/pituitary caboose. Small wonder they are so off the mark with treatment.

[cyberbarn]

If I was peer reviewing this paper, I think I would ask for changes to be made! Interrogate the statistics enough and they will say anything you want.

There wasn't a statement with the paper about involvement of patients, and I suspect that journal doesn't have patient and carer peer reviewers involved. Does anyone know if Thyroid UK supply patient and carer reviewers for journals?

[cyberbarn in reply to cyberbarn]

Just to add, I have gone through the references related to "possible that some patients miss doses and then double or triple the dose prior having their TFTs checked thus resulting in a higher FT4 " quote. It looks like it comes from a paper published in Nepal

"Nevertheless, most of the non-adherent patients reported that they could not access medication easily"

It goes on to say how some were non-adherent due to busy working schedules so missed appointments where their prescriptions would be renewed. It discusses literacy levels and how that affects adherence, as well as health literacy. It was a small study, and the authors themselves say that it wasn't a 'gold standard' one because of the small sample size and self reporting.

And it was in a developing country, so is not comparable to western nations.

As I said, if I had peer reviewed that paper I would have asked them to remove that section about non-adherence and the citation.

[helvella Administrator in reply to cyberbarn]

You'd have to ask lynmynott about whether they have ever supplied anyone, been asked for anyone, or tried to get TUK/member involvement in that way.

I have before now emailed the email contact for papers to ask something or point out an issue. They have always either replied pleasantly or ignored me! But might we worth doing?

TSH110 crabapple

[lynmynott Partner Thyroid UK in reply to cyberbarn]

I'm afraid not. We don't have the capacity to do a lot of things we want to do.

[humanbean]

One thing that research never seems to take into account is that people on Levo-only usually take it all in one go, once a day.

People who are not treated would have any T4 produced by their thyroid being produced in tiny spurts throughout 24 hours a day.

I really don't believe that Free T4 and TSH are ever going to have the same pattern of results when the results of taking tablets are compared to the natural output of a thyroid.

Another thing that occurs to me... Throughout my life I have rarely had blood tests done by the NHS just on a whim. I would usually be complaining of some health problem before I was given blood tests. So the research is never really including healthy people, it is only including people who are, at the very least, not feeling very well.

[helvella Administrator in reply to humanbean]

Valid points - and I agree.