Thyroid hormone homeostasis in levothyroxine-treated patients: Findings from ELSA-Brasil

[helvella]

From paper

Antonio C Bianco has posted on Twitter about this new paper (of which he is a listed author). The first quote below has the image above attached. The second quote has a different image from the paper.

Can this be called normal? Look at T4 and T3 levels in LT4-treated patients with normal TSH. T4 stays high and T3 drops to the bottom of the reference range. This goes on for years, for the duration of the treatment.

twitter.com/Bianco_Lab/stat...

Another view of the same problem. In LT4-treated patients, FT4 distribution shifts to the right and FT3 to the left. While TSH remains normal, many patients have above-normal FT4 and sub-normal FT3 levels. Can we call this "normalization of thyroid function tests"?

twitter.com/Bianco_Lab/stat...

Thyroid hormone homeostasis in levothyroxine-treated patients: Findings from ELSA-Brasil

Gustavo C Penna  1   2 , Isabela M Bensenor  3 , Antonio C Bianco  1 , Matthew D Ettleson  1

Affiliations

PMID: 38506164

DOI: 10.1210/clinem/dgae139

Abstract

Context: The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable.

Objective: To assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study.

Methods:

The ELSA-Brasil study follows 15,105 adult Brazilians (aged 35 to 74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy.

Results:

Initiation of therapy with LT4 resulted in a 11-19% decrease in TSH, a ∼19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and anti-diabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and, a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least one serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least one serum FT3 below the reference range (<0.23 ng/dL).

Conclusion:

The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.

Keywords: TSH; hypothyroidism; levothyroxine; thyroxine; triiodothyronine.

Abstract accessible here:

pubmed.ncbi.nlm.nih.gov/385...

(Apologies, I originally thought the full paper was accessible. Correction made.)

[joydot]

well well…

[helvella Administrator in reply to joydot]

Rosetta isn't better. She is not well, well, well. Because she is on levothyroxine monotherapy.

[RedApple Administrator in reply to helvella]

🤣

[TaraJR in reply to helvella]

LOVE this!

[FAB-jellybean]

At first glance, this doesn't surprise me in the least but will take the time later to read the paper. Thank you helvella

[helvella Administrator in reply to FAB-jellybean]

I don't think the observation is a surprise.

More that it is coming from people within mainstream thyroidology. (Albeit, in the USA.)

[joydot]

shouldn’t be but I am shocked by how much better I am after 2 months back on thyroid-s. The disastrous last 7 yrs were for nothing, as previous tests showed I am now back on what actually works.

[tattybogle]

Good to see the issue publicised so clearly and simply from Bianco . Thanks Helvella

I know he hasn't given up on the 'TSH in range' goal , but having a mainstream Endo publicise this point so clearly re. 'higher T4/ lower T3 / lower TSH on Levo' is a useful opener to conversations with GP's/ endo's re. the potential for this shift to cause us issues long term.

[helvella Administrator in reply to tattybogle]

I agree.

We simply cannot expect a wholesale conversion. And even baby steps are better than nothing or, as has appeared to happen over the years, regression into a an even stronger and less flexible T4-only approach.

[tattybogle in reply to helvella]

pragmatically , there's no point going faster than GP/Endo's can understand.

first get them to acknowledge the ratio's are shifted .

then use this to get them more interested in measuring T4/T3 than they currently are .

then get them to acknowledge that in many instances they find TSH is not doing what they expect for T4/T3 levels .

then ....by about 2050 .. they might place a bit less relevance on TSH during treatment and a bit more on T4/T3/ and other clinical findings .

(in the meantime , if you want it done properly , do it yourself)

I don't expect they'll ever admit they have been arrogantly wrong for decades, but they might start to quietly ignore TSH on treatment .

[helvella Administrator in reply to tattybogle]

The GPs simply won't change until things like NICE guidance change. Which probably takes a sea-change of endo opinion.

But acknowledgement of the right of patients to argue their corners, and be supported by prescriptions, blood tests, etc., even if the GP disagrees would be a huge step across the board. That is thyroid and all other disorders/diseases.

[tattybogle in reply to helvella]

indeed.

[arTistapple]

AHA! I predict an excommunication shortly.

[HealthStarDust]

Reading this makes me tempted to stay off my Levothyroxine for as long as I can bare to get my baseline numbers if possible seeing as I am not getting on well with Levothyroxine alone.

[helvella Administrator in reply to HealthStarDust]

It might be tempting but we have seen many members over the years who have suffered by trying all sorts of tactics to get diagnosed, or treated better.

[FallingInReverse in reply to helvella]

HealthStarDust helvella I have to say that taking a quick scan through this is totally throwing off my outlook on my Levo/Lio strategy.

I was on 50 mcg Levo for 9 months when diagnosed. When symptoms persisted, at that 9 month mark, my doctor put me on 25 mcg Levo + 10 Lio.

I had scary palpitations for almost 9 months... yes, low ferritin and being generally under-replaced probably didn't help. But the Lio kicked those off. And I never got a chance to see how I converted, and - up until reading this article - I was dead set on weaning off the Lio one day.

The rationale is that the vast majority of Hypo folks do well on Levo mono (...right? That's what we always say - those are the millions NOT on this forum.) And personally taking T4/T3 is complicated because I'm chopping up pills all the time, and splitting my T3, and I just find it a pain.

But - this study makes me think that statistically, maybe I'm being silly to think about weaning off my T3. Like... if it was just this study AND the experience of those on this board, I would never ever get off my T3.

Now I'm wondering, who are those T4 mono people that ARE doing just fine??

[helvella Administrator in reply to FallingInReverse]

Imagine we invented an "artificial thyroid" that, like insulin dosing devices, squirted out large numbers of incredibly small doses, directly into the bloodstream. And the doses could be any amounts of T4 and T3.

The first and most obvious approach would surely be to get somewhere near what a real healthy thyroid provides?

The biggest problem being the combination of time from when the thyroid stopped providing the required doses and adjustments the body has made over that time.

So let us simplify to someone who has had a thyroidectomy. And some fancy biochemistry and maths to work out how much thyroid hormone the person was making before the operation.

If you saw they had been making 100 T4 and 10 T3, wouldn't you dial that into the dosing device? Then see how it goes. And make tiny adjustments over time as needed.

The difficulty with prescribing T3 is largely nothing to do with the patient and their bodies.

It is cost. It is unavailability of (automated) micro-dosing. It is ignorance. It is inadequate testing.

I am on levothyroxine monotherapy and believe that I still have some thyroid function. I do quite well. The first reason I do not take T3, and have not even tried it, is that jumping from where I am to taking T3, using what is available in the UK, would start with adding 5 micrograms of T3 a day. And it would only be adjustable by further increments of 5 micrograms. Along with the possibility of needing to adjust my T4 dose which is only possible in 12.5 microgram increments.

I'd also need to monitor by having frequent blood tests

All in all, too precarious, too uncertain, too expensive, and with no certainty of any improvement for me.

But if I could dial in adjustments at the level of about half a microgram of T3 a day (in total), delivered in at least 48 actual doses, I might be tempted. (Obviously using the same device to also deliver T4.) Throw in continuous monitoring - like glucose these days - then the only things that would hold me back are cost and reliability of supply.

[FallingInReverse in reply to helvella]

Can’t agree with you more…

The biggest problem being the combination of time from when the thyroid stopped providing the required doses and adjustments the body has made over that time.

This idea is what gives me a little hope. It took 8 years of a dying thyroid and tons of compensation (marathon training, marathons, and other long distance races… working hard, playing hard, being a night owls, all nighters…). Someone here once said, it took years to get into this mess, it takes time to correct.

But if I could dial in adjustments… delivered in at least 48 actual doses, Throw in continuous monitoring - like glucose these days -

I would spend my last penny on that! To have one of those glucose monitor type discs stuck in my arm, and to have another that releases micro doses of hormones.

In the meantime - after my next titration periods on vitamins I’m going to think very hard about what I do with my T3. I thought I was sure I’d drop it, just not sure now.

[loueldhen in reply to FallingInReverse]

I would argue they're not doing fine - they're told by their GP 'T4 is just a replacement hormone - it can't possibly be that that causes your joint pains, fatigue, brain fog, bloating, weight gain etc', or that they have chronic fatigue syndrome or fibromyalgia and they're so knackered they can't fight it. I'm BLOODY SICK OF IT. We will be dead before they change their mind. (From someone who suffered levo death existence for 7 years - saved myself - T3 only now).

[FallingInReverse in reply to loueldhen]

A couple years ago when I was just diagnosed and feeling awful, I was with an extended friends group and one somehow mentioned they were hypo. They were fine. Or at least actively participating in things and no complaints .I had a friend in college who was hypo on what I presume now was Levo, and they partied it up, blamed a chubby tummy on their thyroid, but was living a normal life.

I do assume that there are plenty of those on anti depressants, statins, joint meds, etc suffering.

But what about the 200 million Levo prescriptions. All those people couldn’t possibly be miserable …

[loueldhen in reply to FallingInReverse]

It's widely estimated that 10-15% don't get on with levo treatment. Clearly a significant number. 300,000-450,000 gaslighted in the UK because of a religious anti T3 zeal. And Simon Pearce is researching into whether he can stop people's levo.... never mind giving them an alternative. There are only two treatment options, I don't care that endos don't understand who does and doesn't respond to each one. They should try a) T4 only, adjust doses b) different formulations of T4 c) combinations of T3 and T4 d) T3 only. I know it''s not quick and simple but I would be dead on T4 only and I've had 10 good years on T3.

[FallingInReverse]

Oh my goodness.

So… the paper is just Levo T4 mono? And that it lowers FT3?

Is that what it’s concluding???

[tattybogle in reply to FallingInReverse]

Yes . when on levo we are getting relatively more T4/ relatively less T3 /with a relatively lower TSH, than we would have had with a properly functioning thyroid gland.

This has been known for a while , lots more papers showing same thing here:

healthunlocked.com/thyroidu.... tsh-is-just-the-opinion-of-your-pituitary-about-your-dose-but-your-pituitarys-opinion-is-a-bit-warped-once-you-take-thyroid-hormone.

[FallingInReverse in reply to tattybogle]

One more layer of this onion.

Like, once seen, can’t be unseen. And… of course!!!! So absolutely obvious.

Mind kinda blown this morning!

[crabapple]

I can only see the abstract.

[helvella Administrator in reply to crabapple]

Abstract accessible here:

pubmed.ncbi.nlm.nih.gov/385...

Apologies, I originally thought the full paper was accessible. Correction made. Entirely my mistake.

[crabapple in reply to helvella]

Thank you. I thought it was me...

[Jumbelina]

Thank you for this image Helvella. It shows at a glance how most of us hypos are affected by levothyroxine. (I do love a chart). It also seems as though most of us are 'bad converters'.