"re-Tweeted" by Simon Pearce ..'evidence' that long term T3 use risks heart failure /stroke ... can anyone get full access ?

[tattybogle]

Link to original tweet by ThyroidFederation:

twitter.com/ThyroidFed/stat...

"The use of combination therapy with liothyronine and #levothyroxine in Asian patients was looked at and found that use of liothyronine was linked with higher incidence of heart failure and #stroke in those with a longer duration of liothyronine use and history of thyroid #cancer.

Link to Abstract of study, full text is behind paywall:

liebertpub.com/doi/10.1089/...

Heart Failure and Stroke Risks in Users of Liothyronine With or Without Levothyroxine Compared with Levothyroxine Alone: A Propensity Score-Matched Analysis

Wook Yi, Bo Hyun Kim, Mijin Kim, Jinmi Kim, Myungsoo Im, Soree Ryang, Eun Heui Kim, Yun Kyung Jeon, Sang Soo Kim, and In Joo Kim

Published Online:8 Jul 2022doi.org/10.1089/thy.2021.0634

"Abstract

Background: Combination therapy with liothyronine (LT3) and levothyroxine (LT4) is used in patients with persistent symptoms, despite being administered an adequate dose of LT4. LT3 may also be used in some thyroid cancer patients preparing for radioactive iodine therapy. However, there is a controversy regarding the safety of LT3 use, and there has been no definite evidence of long-term safety of LT3 therapy in Asian populations. The aim of this study was to examine the long-term safety of LT3 therapy using the Common Data Model (CDM).

Methods: We conducted a retrospective multicenter study across four hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) CDM. LT3 users were defined as those who received an LT3 prescription for at least 90 days (with or without LT4), and their safety outcomes were compared with those in LT4-only users after 1:4 propensity score matching. Safety outcomes included the incidences of osteoporosis, cardiovascular disease, cancer, anxiety disorder, and mood disorder.

Results: We identified 1434 LT3 users and 3908 LT4-only users. There was a statistically significant difference in the incidence rate of safety outcomes between LT3 users and LT4-only users. The risks of heart failure (incidence rate ratio [IRR] = 1.664, 95% confidence interval [95% CI] 1.002–2.764, p = 0.049) and stroke (IRR = 1.757, CI 1.073–2.877, p = 0.025) were higher in LT3 users than in LT4-only users. When subgroup analysis was performed according to the presence/absence of thyroid cancer history and duration of thyroid hormone replacement, the risk of heart failure was higher in LT3 users with a history of thyroid cancer and those who underwent ≥52 weeks of LT3 therapy. In addition, the risk of stroke was higher in LT3 users without thyroid cancer history and those who underwent ≥52 weeks of LT3 therapy.

Conclusions: The use of LT3 was associated with increased incidence of heart failure and stroke in patients with a longer duration of LT3 use and history of thyroid cancer. Therefore, clinicians should consider the risk of heart failure and stroke in thyroid cancer patients with long-term use of LT3. These findings require confirmation in other populations."

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 diogenes .. (wondering if you can access full details) ....if so , do you have any thoughts on the validity / relevance of this evidence ? ..( i notice Johannes Dietrich had replied to thyroid Fed via tweet to ask for details, so wondered if you were aware of this paper. )

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@'Everyone else' ..... as shown below in an Endo's letter that a forum member recently shared with me, this paper is already being quoted by Endo's as evidence .....(in this case the endo is relating it to Armour thyroid use which is a bit of a stretch,) but i expect it will soon be used by many endos' to put people off trials of combination therapy , so i think we need to be looking for ways to counter this paper ... ie does it prove causation over association ?

"Dear Dr •••••••••

I reviewed this lady who has difficult hypothyroidism following treatment for differentiated thyroid cancer. Over the last few weeks •••••••• has built up the dose of her Armour Thyroid to *****// . In addition to the previously documented theoretical risks of taking Armour Thyroid, of atrial fibrillation and it's consequences including stroke and death, cardiovascular disease, reduced bone mineral density, osteoporosis and fracture risk,

I have made ****** aware of new data that has emerged from a study in Korea which looked at patients treated with Liothyronine, either alone or in combination with thyroxine compared to patients on monotherapy. The summary findings were an increased incidence of heart failure and stroke in patients treated with Liothyronine In patients taking T3 for one year or longer there was an increased incidence of heart failure in patients thyroid cancer and an increase risk of stroke in patients who didn't have thyroid cancer compared to Levothyroxine monotherapy. I have made her aware of these findings and while they need confirmation in other studies they should be considered in clinical decisions regarding the use of T3 containing medications."

[helvella Administrator]

The language doesn't say what I think he actually means:

in patients with a longer duration of LT3 use and history of thyroid cancer.

I think he meant:

in patients with a longer duration of LT3 use and in patients with a history of thyroid cancer.

Regardless those who had thyroid cancer have special factors like being subject to high dose radio-active iodine, anti-cancer medications, etc., which make them not comparable to others.

[Francisneat]

I find this very scary! does anyone else? like we don't have enough on our plates

[nightingale-56]

If this is true, then why does NDT give me much better results on a lot of my blood levels, plus I also feel better in myself. The only problem I seem to have with NDT is the excipients in it - Acacia Powder and Cellulose/microcrystalline cellulose? My thoughts are that anything synthetic causes problems.

[tattybogle in reply to nightingale-56]

Note, the actual study ONLY refers to synthetic T3... not Armour ~ linking the study's findings to a patient taking NDT is purely the endo's flawed use of it.

So it says nothing at all about potential risks with NDT use , but i do think we need to look into this study closely to see what they actually found /on who /under what circumstances . to see if we can find a way to stand up to it when it is inevitably used to say "i don't want to prescribe T3 to you because..."

[nightingale-56 in reply to tattybogle]

I did note that it only refers to synthetic T3, so I agree with you that it is a very flawed study. A bit of honesty from medics would be good. Maybe the real reason they don't want to give T3 to us is that they don't know enough about it anyway. If T3 is wrong for us, then why do their bodies make their own T3? We must go on fighting 'them' !

[tattybogle]

and sure enough .. i just noticed BTA are using it in their current "Twitter-spat".

twitter.com/ThyroidBritish (British Thyroid Association Twitter account)

See relevant posts healthunlocked.com/thyroidu... (canadas-tania-sona-smith-powerful-summary-of-recent-btas-twitter-arguments-against-t3)

healthunlocked.com/thyroidu... (voice-your-opinion?)

[Zazbag in reply to tattybogle]

The BTA's tweets are actually sickening.

[tattybogle in reply to Zazbag]

"with friends like these .....who needs enema's "

and no..... that's not a typo

[Zazbag in reply to tattybogle]

Too effing right. In one tweet they actually tried to compare T3 and levothyroxine to organic and budget ginger biscuits respectively, as though T3 is some kind of luxury T4. It's madness.

[tattybogle in reply to Zazbag]

i know .....completely ignoring the fact that T3 is not actually expensive at all .. it's 'expensive' because the endo community and the NHS procurement dept. didn't appear to give a shit when the price magically went up to a gaziilion quid overnight.. and just said 'yeh fine '

following their (rubbish) supermarket analogy ... that would be like the makers of budget ginger biscuits increasing the price by 6000% , and sainsbury's just accepting it and putting them on the top shelf with one of those antitheft tags on., so only rich people could buy them.

[Zazbag in reply to tattybogle]

Amazing analogy! Why are thyroid patients so neglected and disrespected? Is it because were mostly women?

[tattybogle in reply to Zazbag]

Don't think so .. from my observations of posts on here , UK treatment for hypothyroidism is an 'equal opportunities' abuser / gaslighter of anyone unfortunate enough to need it , whatever gender ... doesn't apply to me anyway.. i've always identified as a scarecrow

[Zazbag in reply to tattybogle]

But why thyroid patients?

Do they gaslight diabetics, or cancer patients?

[tattybogle in reply to Zazbag]

They only gaslight the thyroid patients who say . "but i don't feel better with TSH 'normal' " .. if there was 15/ 20% of diabetic patients who said "but i dont feel better with insulin 'normal' " they'd gaslight them too.

They gaslight CFS/ME patients, back pain patients .. and all sorts other patients. Guidleline 42 .. (the answer to life, the universe ,and everything) says "if you can't find it on a MRI , or measure it , or explain it , and it's going to cost the NHS or the benefit system huge amounts of dosh if we say we believe them ....then it's probably in their head "

[Zazbag in reply to tattybogle]

I see what you mean. Even though TSH isn't even a thyroid hormone 🙄

Is Guideline 42 an actual thing?

[tattybogle in reply to Zazbag]

lol , no , you won't find it written down ... but the concept must exist due to the fear of a whopping benefit/ medical bill for supporting anyone who claimed they have a condition for which there was no definitive 'proof' , and therefore having no way to refuse false claims ie. for conditions such as pain, ME/CFS .. or 'Thyroid symptoms with normal thyroid results'.. so it's presumably 'a thing' that influences Gov't and NHS polies , which unfortunately makes it tricky to get proper treatment and support for these type of conditions..

doesn't explain why endocrinology is a specialism that has attracted such a high proportion of spineless tw*ts though...

[Zazbag in reply to tattybogle]

They are awful!

[SarahJane1471 in reply to tattybogle]

😂

[jimh111]

I went to the British Library on Wednesday to get this paper. Unfortunately their system could not print out the Supplementary Material which is needed to see the actual 'propensity score' data which I believe is needed to get the corrected results. e.g. patients on liothyronine may be younger and this might bias the crude results.

First a major flaw. The study does not report doses, resulting in poor quality data. It is well known that higher doses of thyroid hormone carry higher risks of cardiac failure and stroke. Patients on liothyronine will tend to be on higher doses.

My copy of Table S2 which shows the data for the entire cohort is truncated, so I can't see the propensity score data (the final corrected results). However, looking at the crude data we have: - (cancer is reported as 'malignant tumors other than thyroid')

Heart failure LT3/LT4 incidence ratio = 1.467 (p=0.036)

Stroke LT3/LT4 incidence ratio = 1.781 (p=0.002)

Cancer LT3/LT4 incidence ratio = 0.727 (p=0.018)

So, it looks like LT4 therapy is associated with cancer but this is not reported in the abstract or any part of the full document. Hence I need the supplementary material to be sure.

This study is rubbish but so is the first unblinded study in favour of LT3 treatment.

[tattybogle in reply to jimh111]

Thanks Jim.. i'll read your reply properly in a minute or two .. i've just been ambushed by an Aldi All butter Mince Tart with Jamaica Rum mmmm

[diogenes Remembering]

Aha, I thought so: it's the dreaded Pearce doing the talking and walking the walk. He grabs on to a terminally poor paper to beat opponents with - litle realising his stick is really made out of soft rubber. I replied to Lyn Mynott earlier Hope you don't mind me quoting what we said:

This paper is a nonsense. Look at the p values; 0.049 and 0.025 in the various groups. Virtually nonsignificant. And the probability range as low as 1.002. The study is insufficiently powered. As Johannes says, we don’t know what L-T3 doses were given and where FT3 was always within the reference range.You ought to reply to BTA and accuse them of cherry picking to suit their agenda. Here’s another paper saying the opposite:

South Med 2018 Jun;111(6):363-369. doi: 10.14423/SMJ.0000000000000823.

Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of LifeAnam Tariq 1, Yijin Wert 1, Pramil Cheriyath 1, Renu Joshi 

  PMID: 29863229 ·       PMCID: PMC5965938 ·       DOI:10.14423/SMJ.0000000000000823

And this from Johannes Dietrich:

it is not easy to interpret this study. First of all, it is a retrospective analysis evaluating the contents of hospital databases. We don’t know why some patients received L-T3 and others L-T4 only. A common variant of the type 2 deiodinase gene (DIO2, rs225014, c.274A>G / p.Thr92Ala) is associated with both reduced deiodinase activity and preference for T3 therapy, but also with increased risk for hypertension, insulin resistance and type 2 diabetes, which are well-known risk factors for heart failure and stroke. Therefore, we may see considerable bias here.The second point is that older guidelines recommended quite high doses of L-T3, which are considered too high from a modern perspective. I don’t know anything about the guidelines in Korea, but it may be that at least some of the patients received too much L-T3.In summary, we learn nearly nothing from this study.

[tattybogle in reply to diogenes]

thankyou

ah yes . just found ThyroidUK response on twitter....i didn't see that thread before as haven't passed driving test for 'twitter' twitter.com/ThyroidBritish/...

... so far . ... 'BTA' hasn't found any reply to the barrage of proper studies people have chucked back at him.

[diogenes Remembering in reply to diogenes]

I see Bianco has joined in the Twitter condemnation of this paper

[Delgor in reply to diogenes]

😀😀😀

[TaraJR in reply to diogenes]

Yep! All good stuff, to get it aired by more people, and with clinicians disagreeing with him it makes it so much more powerful.

[Hay2016]

maybe we just need to find his nhs email and email him directly to air our views. I can’t Twitter either though I can read it. Im horrified and my husband is equally incensed, and I’d thought he’d side with him as he’s an accountant. 😂

[jimh111]

Got hold of full paper. The study showed LT4 associated with cancer but after Propensity Score the results were non-significant. I think this is because they used 'Charlson comorbidity index' a system that assesses 10 year life expectancy mdcalc.com/calc/3917/charls... . This system ranks 'solid tumor' (the type that T4 promotes) quite highly, especially if it is metastatic. Thus, it is quite likely that the PS matching introduces considerable bias - the harmful effects of T4 on cancer are excluded from the final analysis.