Plasma Metabolomics Reveals Systemic Metabolic Alterations of Subclinical and Clinical Hypothyroidism

[helvella]

This paper does what I have long been waiting for.

Takes some blood, just the serum, and do a comprehensive analysis of pretty much everything they can detect in that serum.

The subjects were divided into Control, Subclinical Hypothyroid and Hypothyroid groups.

They found clear differences between Control and the other two group. Somewhat less clear between Subclinical Hypothyroid and Hypothyroid.

Hands up if you are amazed by that! The authors do seem a little surprised.

I suggest that the definitions of Subclinical Hypothyroid and Hypothyroid are deeply questionable. Indeed, some of the results of this study might do a better job than do existing definitions.

Unsurprisingly to many here, T3 is slightly higher in Subclinical Hypothyroid and then drops in Hypothyroid. While T4 drops a bit in Subclinical Hypothyroid and much further in Hypothyroid. Which supports the idea that the body does what it can to protect T3 levels.

There is lots and lots more to read.

Maybe, in time, we'll see chasing blood levels of hormones as an exercise doomed to failure. If you can determine hypothyroidism by changes in metabolism, you could even take two people with identical thyroid hormone levels and see that one is hypothyroid, the other not. Thyroid hormone levels would still need to be tested - if only to double-check.

This study uses serum. Can they do the same with urine or saliva? What would those studies show?

Can they produce analysers that cost far, far less but which can identify and measure the most important compounds?

Plasma Metabolomics Reveals Systemic Metabolic Alterations of Subclinical and Clinical Hypothyroidism

Feifei Shao, Rui Li, Qian Guo, Rui Qin, Wenxiu Su, Huiyong Yin, Limin Tian

The Journal of Clinical Endocrinology & Metabolism, dgac555, doi.org/10.1210/clinem/dgac555

Published:

01 October 2022

Abstract

Context

Clinical hypothyroidism (CH) and subclinical hypothyroidism (SCH) have been linked to various metabolic comorbidities but the underlying metabolic alterations remain unclear. Metabolomics may provide metabolic insights into the pathophysiology of hypothyroidism.

Objective

We explored metabolic alterations in SCH and CH and identify potential metabolite biomarkers for the discrimination of SCH and CH from euthyroid individuals.

Methods

Plasma samples from a cohort of 126 human subjects, including 45 patients with CH, 41 patients with SCH, and 40 euthyroid controls, were analyzed by high-resolution mass spectrometry–based metabolomics. Data were processed by multivariate principal components analysis and orthogonal partial least squares discriminant analysis. Correlation analysis was performed by a Multivariate Linear Regression analysis. Unbiased Variable selection in R algorithm and 3 machine learning models were utilized to develop prediction models based on potential metabolite biomarkers.

Results

The plasma metabolomic patterns in SCH and CH groups were significantly different from those of control groups, while metabolite alterations between SCH and CH groups were dramatically similar. Pathway enrichment analysis found that SCH and CH had a significant impact on primary bile acid biosynthesis, steroid hormone biosynthesis, lysine degradation, tryptophan metabolism, and purine metabolism. Significant associations for 65 metabolites were found with levels of thyrotropin, free thyroxine, thyroid peroxidase antibody, or thyroglobulin antibody. We successfully selected and validated 17 metabolic biomarkers to differentiate 3 groups.

Conclusion

SCH and CH have significantly altered metabolic patterns associated with hypothyroidism, and metabolomics coupled with machine learning algorithms can be used to develop diagnostic models based on selected metabolites.

subclinical hypothyroidism, clinical hypothyroidism, metabolomics, thyrotropin, free thyroxine, biomarkers

Open access here:

academic.oup.com/jcem/advan...

[tattybogle]

ooh ... that looks interesting... will comeback and read it once i've found some gloves to put on. ....is winter nearly over yet ? .... i've been using £7 /day of gas since friday to keep some bits of the house tolerable for other people, which is a bit terrifying ... today i'm about to find out how 'tolerable' it is in here if i don't turn it on .

[DippyDame]

The importance of T3 is not flagged up in this abstract and that is enough to send me off on another rant!!

How much did these researchers know about thyroid function and thyroid hormones at the outset? They seem surprised at what I suspect many here have long since concluded...

Either we are hypothyroid or we are not?

Sub meaning under!

How does the medical profession define subclinical hypothyroidism? Sounds like either a convenient excuse to avoid medicating signs and symptoms they don't fully understand or lack of knowledge.

Definition of SCH

Subclinical hypothyroidism is defined biochemically as a normal serum free thyroxine (T4) concentration in the presence of an elevated serum thyroid-stimulating hormone (TSH) concentration.

Again we see TSH flagged up as a defining factor in diagnosis but with no reference to FT3 which, as the active thyroid hormone is the most important marker

Why is that TSH elevated?.

Most likely because FT3 is low...the pituitary then detects this In an overall low thyroid hormone level in the serum it then signals the thyroid to produce more hormone. This keeps FT4 at a " normal" level which leaves TSH elevated and FT3 still at an (undetected) low level. Is T4 to T3 conversion the problem

The system is expected to convert that increased level of T4 to T3....but conversion may be impaired!

Which supports the idea that the body does what it can to protect T3 levels.

The word " normal" is itself misleading and usually means " in range" and for individuals this means nothing when what they really need is to have a reading that sits on a specific point within the range

Thyroid patients would receive better diagnoses and treatments if T3 was routinely tested and medics understood why that is so vital for their patients wellbeing.

metabolite alterations between SCH and CH groups were dramatically similar

So were they all actually hypothyroid!!

If T3 is low we suffer....are medics and researchers missing this point?

Thyroid hormone levels would still need to be tested - if only to double-check.

The problem here is that they don't always check both thyroid hormone levels....but rely instead on T4 only along with TSH a pituitary hormone.

machine learning algorithms can be used to develop diagnostic models based on selected metabolites.

Maybe.....but, as far as thyroid disease is concerned is this going to readily answer the problems that robust thyroid testing and indepth understanding of clinical evaluation cannot?

Are they taking a sledge hammer to crack a nut!

[helvella Administrator Thyroid UK in reply to DippyDame]

I think there is a possibility that this sort of approach might help to crack that nut.

After all, however we measure them with current technology, TSH+FT4+FT3 are always going to be a snapshot of that moment.

We often point out that high cholesterol is associated with hypothyroidism. And suggest it will likely drop with adequate treatment. Which is fine and true. And you can easily see that anyone being treated has patterns of rise and fall in thyroid hormone levels due to dose(s) and timing. So we could see the TSH+FT4+FT3 test results at any point whatsoever within their daily variations - with total cholesterol pretty static through every day and night. In that case, frequent (many times a day) TSH+FT4+FT3 testing has potential. But Total Cholesterol gives a decent indication.

Add numerous other factors that can be measured. You could end up in a good place.

(Maybe it's just wishful thinking? Still, at least it's something for me to be positive about. )

[Aurealis in reply to DippyDame]

I love your “rant” DippyDame but I think you’re underselling it there, it’s a beautifully expressed concise but detailed statement. Very useful to many I expect. It’s just where we’re at. 👏

[DippyDame]

Agree we all need to have something positive.....it's grim out there right now.

I just wish "they" would come of their high horses and get to grips with the importance of T3 at cellular level

Patients are suffering untold miseries without what should be basic therapy.....that is the priority right now.

Maybe I'm just an old grouch, but it makes me furious when I read daily posts about suffering caused by poor basic diagnoses and medication....way down the line from Metabolic Alterations.

No point in building a mansion if the foundations are weak!

Stay warm!

[Aurealis]

thanks for posting, very interesting

”Maybe, in time, we'll see chasing blood levels of hormones as an exercise doomed to failure”

I already do! But I don’t expect established ‘wisdom’ to change in my lifetime… I did once, but we’ve gone backwards now