Letter from Bianco's & Hoang's labs defending u... - Thyroid UK

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Letter from Bianco's & Hoang's labs defending use of T3 and DTE in treatment

diogenes profile image
diogenesRemembering
42 Replies

This letter is a reply to a rather critical one from Bonnema. It doesn't have a doi number so I've put it here in full. My only gripe is that they insist on " normal" TSH as being proof of proper dosing. However they don't damn the use of NDT(DTE). One can take heart from that.

Dear Editor,

We thank Bonnema et al 1 for giving us the opportunity to provide further details on our recent publication 2 while addressing their insightful questions.

1. In reference to the consequences of long-term treatment with LT3, we respectfully point out that there is now solid data that LT3 does not increase the frequency of adverse reactions if serum TSH levels are maintained within the normal range. For example, an observational study during 1997-2014 3 that compared nearly 34,000 patients taking only LT4 with those using LT4+LT3 (n = 327) or LT3 alone (n = 73) during a mean follow-up of 9.3 years (SD 5.6) and a maximum follow-up of 17.3 years. The study did not reveal higher mortality or morbidity risk due to cardiovascular disease, atrial fibrillation, or fractures. In addition, an analysis of 20 clinical trials that included almost 1,000 patients observed for up to 1 year indicated that peaks of serum T3 observed after the LT3 tablets only minimally affected serum TSH, heart rate, and blood pressure; the frequency of adverse reactions was similar to patients taking LT44 . Bone turnover markers were studied in two trials, and they remained within normal range. This was confirmed in a recent meta-analysis by Millan-Alanis et al 5 in which 18 clinical trials comparing LT4 vs LT4+LT3 therapy were evaluated found no differences in adverse events. In fact, we are unaware that combination therapy containing LT3 has ever been associated with increased occurrence of adverse reactions in patients maintaining normal TSH levels. (Hmm, my interjection).

2. In reference to a potential placebo effect associated with “entering a trial”, we found that 20 patients comprised the subgroup with the worst outcomes while on LT4 therapy and these patients were randomly distributed across the 3 treatment arms. 7 patients received LT4 on Arm-1 and 9 patients received LT4 on Arm-2. Thus, it is unlikely that a placebo effect played a role.

3. Baseline values were considered in the analyses. As stated under methods, differences between treatments were evaluated using mixed effects models. The primary outcome model included a fixed effect for treatment and a random effect of subject. Models were run with and without the inclusion of baseline scores to isolate between treatment differences. In the sub-analysis we also considered the baseline values but were not able to detect differences between baseline and LT4-treated arm.

4. In reference to a subgroup analysis of patients on DTE or LT4+LT3 prior to the trial, we found that there were 8 patients on DTE and 3 patients on LT4/LT3 at baseline. At the end of the study, out of these 11 patients, 6 preferred DTE and 5 preferred LT4/LT3 combination. This suggests that a placebo effect could not explain our findings. An appropriately powered study could address this point further. Of note, a preference for DTE had already been identified in our previous study6 . It has been our experience that most patients taking DTE show strong preference for continuing on DTE rather than switching to LT4.

Lyn Mynott - I found the url - tinyurl.com/2s3uhpey

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diogenes profile image
diogenes
Remembering
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42 Replies
pennyannie profile image
pennyannie

So, as it's not normal not to have a thyroid Is it possible that those of us having had medical intervention and a thyroidectomy or RAI be given " a bye " on the " normal TSH dogma. " ?

StitchFairy profile image
StitchFairy in reply topennyannie

Can you explain why not having a thyroid due to medical intervention should be treated differently to those of us who have totally a 'dead' thyroid due to destruction by the immune system for example? Or am I misunderstanding what you're saying?

diogenes profile image
diogenesRemembering in reply toStitchFairy

It is simply because when the thyroid is lost, its significant and direct contribution of T3 is also lost. If you have then to take say T4 only, you have to take more T4 than is normally produced by the healthy thyroid, because the body's T4-T3 conversion has now to take the whole strain to achieve the FT3 which is optimal for you in health. With this the TSH from the pituitary is partly suppressed. It's the same for T3 only, but this has a big effect in suppressing TSH.

StitchFairy profile image
StitchFairy in reply todiogenes

But isn't that also the case if the thyroid is 'theoretically' there, but has been killed off by the autoimmune process and doesn't produce any hormones?

diogenes profile image
diogenesRemembering in reply toStitchFairy

Yes

TSH110 profile image
TSH110 in reply toStitchFairy

I was told mine was highly unlikely to have any function at all during the ultrasound. It had atrophied due to auto immune thyroiditis. So mine, the tiny crisp of thing that remains, does nothing.

pennyannie profile image
pennyannie in reply toStitchFairy

I'm simply trying to make a point of cause and effect by the medical profession :

I just thought the consequences and implications of such a medical procedure might be better explained in a guideline for those people who have no idea of the ramifications.

I read people who have had a thyroidectomy are looked on as more likely to get prescribed T3 - whereas RAI - Graves people seem to be totally dismissed as needing anything at all after being " treated " with having to ingest a toxic substance :

Of course, with any auto immune thyroid disease there is a need for more than T4 monotherapy and I was just trying to make a notch in the restrictive, unbending rules and guidelines that seem so blindly followed by medical professionals who don't seem to have an understanding on basic human anatomy and physiology.

TSH110 profile image
TSH110 in reply topennyannie

We should ALL have freedom of choice between T4, NDT, T3/4 combi or T3 alone

pennyannie profile image
pennyannie in reply toTSH110

No argument :

TSH110 profile image
TSH110 in reply topennyannie

Seems a lot of men in White coats can argue about it till the cows come home 🙄 what’s it to them? Most them will never need to take any thyroid hormones but they seem determined to stop us from having our say and our way 😠😡🤬

pennyannie profile image
pennyannie in reply toTSH110

Well, it's paying the mortgage isn't it and keeping them in white coats :

Lots of content and no action and repeat again in a few years time :

TSH110 profile image
TSH110 in reply topennyannie

I couldn’t live with my conscience behaving like that!

pennyannie profile image
pennyannie in reply toTSH110

No, I know, maybe they don't have mirrors to look into ???

TSH110 profile image
TSH110 in reply topennyannie

Through a glass darkly….pity they have to be about to croak to see it all clearly!

jgelliss profile image
jgelliss in reply toTSH110

We need to look for Dr's that either they or their loved ones have thyroid issues so they can understand what we are going through.

jgelliss profile image
jgelliss in reply toTSH110

I totally agree with you. I don't really understand why all the fuss is made. Patients know best what feels right for them. Why can it not be respected? I still say the Medical Academia needs to put more time and effort into educating Dr's about thyroids and thyroids meds .Not only about T4 and how it converts to T3 . And that's supposed to fix it all. Dr's should be educated in nutrients too while we are at it .We are not asking for much. We only want to feel as well as possible.

TSH110 profile image
TSH110 in reply tojgelliss

👏🏽👏🏽👏🏽

tattybogle profile image
tattybogle in reply tojgelliss

I agree , I think we should insist on it being a requirement to have the thyroid removed before qualifying as an endocrinologist and before they are given any patients to play with .

(or at least, a quick dose of RAI , if having surgery was considered a bit 'unnecessary' )

After all , would you take your car to a garage where the mechanic had never driven a car on the road ..... i think not .

and I'm only half joking .......

jgelliss profile image
jgelliss in reply totattybogle

Ditto. So well said. Thank You.

Mollyfan profile image
Mollyfan

The problem for Bianci here is that ( as far as I am aware) almost all trials have been done while explicitly keeping TSH in range. He does not say that there is evidence of problems if TSH is too low, nor does he say there isn’t because there just is not the evidence one way or the other. I am looking forward to his book!

TSH110 profile image
TSH110 in reply toMollyfan

There must be something covering NDT it was used for so long. I believe Broda Barnes found better health outcomes for those on NDT than the general population.

in reply toMollyfan

Exactly my reaction! Many of us cannot maintain a normal TSH when on NDT/T3.

TSH110 profile image
TSH110 in reply to

Cos we are properly medicated so why would there be a signal to make more thyroid hormones when there are enough in circulation in our bodies ? Of course TSH will become suppressed or you’re not getting enough medication. Isn’t it blindingly obvious to these white coats? Clearly not. I wonder what they really understand about the thyroid - not a lot I’d say. They don’t even comprehend the basics hence their preposterous models small wonder so many thyroid patients fell unwell with those charlatans driving treatment protocols. I hope one day diogenes and colleagues ‘ groundbreaking research will prevail and their incorrect assumptions will be consigned to the dustbin of history.

jgelliss profile image
jgelliss in reply to

Exactly. Many who had TT and need to be suppressed are better off with some T3 with lower dose T4 than high doses of T4 sole. T3 is great for suppression.

in reply tojgelliss

Definitely! The problem is that many doctors are terrified of a low or suppressed TSH. They seem unable to tell the difference between hyperthyroidism (overactive thyroid) with out-of-range free T3 and T4 and TSH suppression from T3 with in-range free T3 and T4.

jgelliss profile image
jgelliss in reply to

Oh !You are so Spot On.

humanbean profile image
humanbean

This letter is a reply to a rather critical one from Bonnema.

Has the letter from Bonnema been published? If yes, do you have a link or a description to where it could be found?

diogenes profile image
diogenesRemembering in reply tohumanbean

I cannot get it complete as it is behind a paywall. However, this is the source doi number: Someone might be able to bypass. I'll try to get one of our coworkers to access.

Letter to the Editor

From S.J. Bonnema et al: “Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism”

Steen Joop Bonnema, Kamilla Ryom Riis, Christian Zinck Jensen, Marianne Thvilum, Birte Nygaard

The Journal of Clinical Endocrinology & Metabolism, dgab778, doi.org/10.1210/clinem/dgab778

humanbean profile image
humanbean in reply todiogenes

Thank you.

...

Just to recap and make sure everyone, including me, understands the sequence of events

1) A paper was published by Shakir et al. This one :

Title : Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism by Shakir et al

Link : academic.oup.com/jcem/artic...

2) Bonnema et al wrote a letter in response to the above paper, and this is the link and the Extract :

Link : academic.oup.com/jcem/advan...

Extract

To the Editor:

Shakir et al (1). recently published their results from a highly relevant randomized clinical trial in patients with hypothyroidism. Seventy-five patients, the majority being on levothyroxine (LT4) before enrollment, were in a cross-over design treated with either LT4, LT4+liothyronine (LT3), or desiccated thyroid extract (DTE). Each treatment was given for 22 weeks. Impaired quality of life parameters were not part of the inclusion criteria. Scores on symptoms, mood, general health, and cognition were assessed after each treatment period.

No differences were found between the 3 regimens, and the patients, as a group, had no treatment preference. In a subanalysis, the patients were stratified into terciles according to their performance scores. The third of patients with the poorest performance, while on LT4, improved their scores when switching to 1 of the other regimens. Accordingly, the authors concluded that symptomatic patients on LT4 might benefit from LT4+LT3...

3) And now Bianco et al have written a reply to Bonnema's letter which is given in the first post in this thread.

Gingernut44 profile image
Gingernut44

Thank you for posting. It worries me that they keep referring to TSH in range. My local NHS lab has set the TSH upper limit at 5. As many patients know only too well, with a TSH that high, we can feel extremely hypo. How is the insistence of keeping TSH in range going to help us when battling with ignorant GPs.

helvella profile image
helvellaAdministrator in reply toGingernut44

Whilst I agree with you, I think that in this specific case, they mean "not below range".

But it really doesn't help. And far too often we have this approach:

"When I use a word," Humpty Dumpty said, in rather a scornful tone, "it means just what I choose it to mean—neither more nor less."

Humpty Dumpty illustration by Tenniel
Gingernut44 profile image
Gingernut44 in reply tohelvella

Well, if that’s what they mean, why don’t they say so. Keeping TSH in range, as you say, can mean anything a GP wants to say. Can you put me back together again - no, you’re not broken - get back on your wall 🤪

TSH110 profile image
TSH110 in reply toGingernut44

Why can’t they use free T3 as their guide to dosing? I rue the day TSH was discovered to then take centre stage 😖

Gingernut44 profile image
Gingernut44 in reply toTSH110

Me too

jimh111 profile image
jimh111

The original study is here doi.org/10.1210/clinem/dgab478 .

The Bonnema doi.org/10.1210/clinem/dgab778 reply is behind a paywall.

The Bianco team response doi.org/10.1210/clinem/dgab779 .

I've not read them yet. Thanks for posting.

tattybogle profile image
tattybogle

Thanks for 'keeping us posted ' :)

Yeswithasmile profile image
Yeswithasmile

Thank you for posting.

It’s interesting and I would interpret as good progress.

It will be fantastic when they finally concede that tsh is frequently surpressed with inadequate levels of hormone replacement and that the conventional view of ‘over’ medicating may actually be ‘optimally’ medicating.

JGBH profile image
JGBH

Thank you for the post.

diogenes profile image
diogenesRemembering

The real difficulty with Bianco and all other thyroidologists is that they believe only in the importance of the TSH-FT4 interface, and that FT3 has only a little part to play in control. This then spills over into the mistaken idea that the TSH healthy range is suitable for the treated range. The field in general cannot get their heads round the change that we've discovered that T3 either direct from the thyroid or converted from T4 in the body has an essential role to play in overall control, and that this has implications for the success of treatment and what part TSH has to play.

tattybogle profile image
tattybogle in reply todiogenes

have you considered sending all of them a signed portrait of Nicolaus Copernicus ?

( with the words "do keep up " in a speech bubble )

TSH110 profile image
TSH110 in reply totattybogle

Love it!!

TSH110 profile image
TSH110 in reply todiogenes

Why are they SO STUPID? Do they ever read anything showing their ideas are not in keeping with current knowledge? They must be really thick! Even I get it!! Perhaps I should knit them all a brain….sigh

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