Debate Continues on Combination Therapy for Hypothyroidism

[helvella]

Antonio Bianco has updated the discussion on combination therapy.

The links might well not work if you are not logged into researchgate - hence I have quoted the update:

39m ago

Antonio Bianco

added an update

Debate Continues on Combination Therapy for Hypothyroidism - Medscape - May 20, 2022, by Miriam E. Tucker

It's "critically important" for clinicians to recognize that not all patients with hypothyroidism are fully treated with levothyroxine(LT4) and some may need combination treatment with triiodothyronine (LT3) despite normal levels of thyroid-stimulating hormone (TSH), according to thyroid expert Antonio C. Bianco, MD, PhD.

Speaking to a crowded room at the recent American Association of Clinical Endocrinology (AACE) Annual Meeting 2022, Bianco summarized the history of thyroid replacement treatment, the emerging data focusing on the subset of patients remaining symptomatic on levothyroxine, and how the clinical guidelines have evolved from stating that LT4 is the one and only treatment to now acknowledging that some patients may need combination therapy.

"Treatment with LT4 will leave residual symptoms in about 10%-20% of the patients. Before planning a thyroid surgery, this issue should be discussed with patients. We used to tell patients that LT4 treatment resolves all symptoms, but this is not true for all. For those...who remain symptomatic while on LT4, physicians should attempt combination therapy," Bianco told MedscapeMedical News.

The acknowledgement, he said, is "critically important because patients are greatly aggravated by the fact that physicians are satisfied with a normal serum TSH and yet they do not feel well.

This comes out in every survey we and others have done."Common residual symptoms include weight gain, fatigue, and "brain fog," which clinicians sometimes dismiss as psychological, he noted.

However, Bianco cautioned that before attempting combination therapy, it's important to make sure that patients don't have other comorbidities that could explain the residual symptoms, including perimenopause/menopause, obesity, vitamin B deficiency, anemia, or other autoimmune diseases.

Bianco is a professor of medicine at the University of Chicago and the author of more than 80 publications on the thyroid as well as an upcoming book.

researchgate.net/project/Re...

Link to PDF:

researchgate.net/profile/An...

diogenes

[tattybogle]

OOh .. we've been promoted from 'dissatisfied' to 'greatly aggravated ' ...nice .Hope NICE are reading it too .

[TSH110 in reply to tattybogle]

It’s certainly made me feel greatly aggravated 🤣😡🤣🤬🤣

[helvella Administrator]

However, Bianco cautioned that before attempting combination therapy, it's important to make sure that patients don't have other comorbidities that could explain the residual symptoms, including perimenopause/menopause, obesity, vitamin B deficiency, anemia, or other autoimmune diseases.

If other specialists took the same approach that endocrinologists have...

The menopause specialists will insist any remaining symptoms are due to obesity, vitamin B deficiency, anemia, other autoimmune diseases or thyroid.

The obesity specialists will insist any remaining symptoms are due to perimenopause/menopause, vitamin B deficiency, anemia, other autoimmune diseases, or thyroid.

[I think you've got the picture by now... ]

[pennyannie in reply to helvella]

And the TSH has to play ball and to be within the guidelines ?

[TSH110 in reply to helvella]

Always the cart leading the horse with those stupid endocrinologists 🙄

[Hennerton]

Thank you for posting this and it is good to see that someone is flying the T3 flag.

One point that seems odd, however, is the statement that Comorbidities might be the cause of the patient’ dissatisfaction and this possibility should be checked before allowing T4/3. Sorry but a simple blood test that shows poor levels of T3 will be all that is required.

When I was diagnosed as needing it, my T4 was over range, as I clearly wasn’t converting properly, yet T3 was well under range. TSH was low because of my high T4. Isn’t that clear enough? Why make it once again the patient’s duty to prove that they are not depressed, or whatever alternative is being suggested?

[helvella Administrator in reply to Hennerton]

The endocrinologists seem to be of the opinion that T3 levels vary far too much - in size of swing and rate at which swings occur - to be of much use.

Perhaps the simple fact that so few FT3 tests are done means they are never disabused of this false notion?

I'd also add that if the endocrinologists are convinced that these other issues are to blame, why don't they refer all patient with residual symptoms to the specialist in these other issues?

I guess that for vitamin B, a prescription for a decent B-complex might do a lot to resolve symptoms. (Just adding that this was meant to question why they don't simply do something like this rather than nothing?)

[pennyannie in reply to helvella]

My T3 and T4 blood test results have been pretty much stable for the last 4 years since I started self medicating.

It's belittling reading of these stupid excuses from a bunch of medical professionals whom I once respected and trusted as knowing how to help me get better.

[TSH110 in reply to helvella]

Endocrinologists need to smarten up their act. I’d like to give them a hefty kick up the backside but I bet even that would not shift them out of their predjudices

[jimh111]

I'm away from home so brief comments.

1. These figures are based on the hypothyroid patients who get a diagnosis, invariably with a high TSH and low fT4. There are many without a diagnosis and the nature of their hypothyroidism means that a much higher proportion will need T3, often at higher doses.

2. Levothyroxine monotherapy works fine for many patients with primary hypothyroidism. I've always supported this. However, my recent research shows that this strategy leads to increased cardiac and cancer risk. Therefore I feel that levothyroxine monotherapy should only be used in exceptional cases. Combination therapy should be standard because it will not only help patients feel better but more importantly they will live longer and stay healthy longer.

[helvella Administrator in reply to jimh111]

I suggest that widespread combination therapy is likely so far away that we'll never see it.

[jimh111 in reply to helvella]

True, but it's important to point out combination therapy is safer than monotherapy. This is so we can counter false claims that T3 is more harmful than T4.

[TSH110 in reply to helvella]

We must keep demanding it

[Hennerton in reply to jimh111]

What would you consider to be an “ exceptional case”. I cannot think of any case that would warrant no T3, particularly if you are now flagging up cancer and cardiac risks with Levothyroxine used alone.

If T3 is too potent for some people, they can take a tiny dose, as recommended by the late Dr Skinner to me. I was cutting up a tiny Liothyronine tablet in my first week of taking it and found the tiniest crumb was effective. Gradually I increased the size of the crumb but even now many years later, 5mcg is enough for one dose for me but taken twice a day.

[helvella Administrator in reply to Hennerton]

The other day there was a post which quoted a paper. In that, it said some people might be best using levothyroxine alone - depending on combinations of genes.

[Hennerton in reply to helvella]

Was that for people with no thyroid? I doubt it. I honestly think it is hopeless to put thyroidectomy patients in a bundle with hashimotos patients and expect to use the same study for both.

[BB001 in reply to Hennerton]

Don't forget those people that haven't had a thyroidectomy operation because their own immune system did it for them! We're the totally forgotten ones.

[TSH110 in reply to BB001]

I’d say being ignored is across the board. Look at the hoops that need to be jumped just to get Levothyroxine monotherapy with TSH over 10 on two occasions huge numbers are just being left to rot. I’m an atropic autoimmune thyroiditis mine actually did die just as I finally got treatment - god I was in a pitiful state

[TSH110 in reply to helvella]

Are they intending to do mass thyroidectomy then 🙄 so everyone can. have gold standard Levothyroxine and no T3 what soever it’s so dangerous. When are these dummies going to wake up?

[jimh111 in reply to Hennerton]

Exceptional cases would include those people who just cannot get on with liothyronine or NDT. It could also include people with mild thyroid failure or perhaps they have had a bit of their thyroid removed and just need a little top up.

Also people with Graves' antibodies and no functioning thyroid. In this case the TRAb (strictly speaking TSH stimulating antibodies) will stimulate excess T4 to T3 conversion so they are unlikely to want additional T3. They may need T3 after the TRAb have gone.

The cardiac and cancer risks are associated with T4 levels, even within the reference interval. So, it's better to have a low normal fT4 than a high normal or elevated fT4. Combination therapy will allow people to recover with a low normal fT4 and around average fT3 although some will need higher fT3 levels.

[TSH110 in reply to Hennerton]

If it’s too potent for people those with a functioning thyroid should be treated to stop it being made! This whole argument they used is plain ridiculous!

[TSH110 in reply to jimh111]

Totally agree

[diogenes Remembering]

While I am truly behind and support Bianco and colleagues in their findings, they stumbled on this many years after our start point of 2012. It's good to see them finally criticising the illegitimacy of doing clinical trials on all hypothyroids on T4, and belatedly realising that subgroups can be swamped by the findings in the major group. Looking at the way the subject is progressing (and its timescale) there can be no doubt that our papers have been the stimulus for their self-advertisement (indeed the term homeostasis in thyroid matters, as now understood, emanates from our early paper in 2012). The problem is as always: if anyone outside the accepted clique discovers anything important, they will be sidelined by takeover without much or any acknowledgement. This isn't limited to thyroidology - academics can be like magpies, if they see anything worth stealing.I'm afraid Bianco is a prime example (his forthcoming book will demonstrate this). And I look forward? to the parroting by the UK (gurus?) of the decisive work, thereby effectively recreating the bicycle long after it has been discovered elsewhere. BTW one of our new papers hints that combination therapy may be appropriate for a larger subgroup that is currently believed to exist. If we can only get TSH recognised as a faulty diagnostic in therapy then the stage should be set for a complete rethink in this field.

[pennyannie in reply to diogenes]

Your last sentence has to be the most important sentence of all.

Reliance on a TSH reading once on any form of thyroid hormone replacement has to be the biggest issue to tackle and has sadly restricted so many peoples thyroid journeys back to better health.

Thank you for all you do - it is greatly appreciated.

[BB001 in reply to diogenes]

Interesting... 'one of our new papers hints that combination therapy may be appropriate for a larger subgroup that is currently believed to exist'... I look forward to reading it.

How long do you think it will be before other researchers assume that idea for their own?

[FancyPants54]

What's obesity got to do with it! Another excuse to beat us with? Obesity is a symptom of hypothyroidism not a reason not to treat it properly.

[pennyannie in reply to FancyPants54]

Exactly - everything but the solution :

[helvella Administrator in reply to FancyPants54]

Various pollutants have also been identified as possible causes of both hypothyroidism and obesity unrelated to hypothyroidism. The old double-whammy.

[Quite likely fully proved, but I am not in a position to find definitive proof to back that up.]

[FancyPants54 in reply to helvella]

You would think it not beyond the wit of man and GPs to realise that their once fit, slim and healthy patient who has just been diagnosed with hypothyroidism and gained 3 or 4 stone in rapid rate might actually have a connection between the 2 going on. But no. Obesity is our fault. Mind you, so is hypothyroidism in many of their minds.

[BB001 in reply to FancyPants54]

Here's another one...

Our symptoms not going away when treated with levothyroxine is classed as our fault for being 'non- compliant' with medication.

[FancyPants54 in reply to BB001]

Of course it is. Despite us being diligent, it has to be our fault. Not their fault of misunderstanding how all this works and how to treat it successfully.

[lolajone]

Pollutants? Not heard this before?

[helvella Administrator in reply to lolajone]

Which part? Obesity or thyroid issues?

This is just a link to a newspaper article but there are quite a few papers on the issues.

Environmental toxins are worsening obesity pandemic, say scientists

Exclusive: Pollutants can upset body’s metabolic thermostat with some even causing obesity to be passed on to children

theguardian.com/environment...

[arTistapple in reply to helvella]

You know helvella, I have just read the Guardian article you tagged. I am aware of this stuff from some years ago. However the point or issue I would like to make here may seem at first entirely unrelated - even be seen as a factor in my own “Thyroid Madness”. I could have been reading about the Russian invasion of Ukraine. Stay with me here. The utter madness and stupidity of a small number of human beings, for the sake of legacy, riches, selfishness, no worthwhile actual vision, arrogance and utter lack of empathy, being able to exercise their ignorant power over others. Never have I felt more angry and powerless. Where is the shining light and acceptable authenticity and integrity in medical research which is/should be capable of giving us our lives back? Grrr! Thank you for all your input. I appreciate very much your interest. I am roused. Will I manage to get anything else done today?

[TSH110 in reply to helvella]

I’d think a good way to nullify the effects of toxins that shouldn’t be there would be to wrap it up in a good old dollop of fat.

[helvella Administrator in reply to TSH110]

Doesn't work with airborne substances such as lead from leaded petrol or lead smelting works!

[TSH110 in reply to helvella]

I must read the article. I suppose they just disrupt the body and upset all the fine balances, like illness can do. I have noticed those I know who have got cancer seem to have put on weight in the run up to diagnosis.

[humanbean]

it's important to make sure that patients don't have other comorbidities that could explain the residual symptoms, including perimenopause/menopause, obesity, vitamin B deficiency, anemia, or other autoimmune diseases.

I'm hoping this is just a poorly constructed sentence. If someone is obese because they are hypothyroid, denying them treatment for the hypothyroidism won't make the obesity go away. And being obese won't reduce the need for T3 if the patient needs it. The patient who is obese and hypothyroid is very unlikely to be able to lose weight at all without adequate thyroid hormone levels - and it is still a huge struggle to lose it even then.

I'm also curious... I could never tolerate HRT so I have no idea of its effect on hypothyroid women. But Bianco's sentence above suggests that women can't be both hypothyroid and menopausal at the same time, which is obviously total nonsense.

Doctors are so scared of thyroid hormones that they will pull any excuse out of a hat to avoid treating the patient who needs them. And they are even more determined to avoid giving out T3. They claim that it's because it's dangerous, but we all know it's because of the price, at least in the UK.

One of the things that doctors never take into account is that thyroid hormones are NOT like being on speed or cocaine or heroin. Too much doesn't make people feel wonderful, it makes us feel awful. And an obvious point - if having too much thyroid hormone was so wonderful why does anyone who is hyperthyroid ever seek treatment?

I have this mental image of medical students buying Levo and T3 pills in the toilets from drug dealers because they think it must be great.

[helvella Administrator in reply to humanbean]

Have to say, I purposely wore blinkers to read that. I could see many possible interpretations but didn't follow them.

[RedApple in reply to humanbean]

humanbean 'Bianco's sentence above suggests that women can't be both hypothyroid and menopausal at the same time, which is obviously total nonsense.'

I have always been of the opinion that if thyroid hormones are out of whack, the other hormones are almost certainly going to be affected too. Treat the thyroid hormone imbalance first, and the 'sex' hormones may stand a chance of gradually sorting themselves out.

[humanbean in reply to RedApple]

100% agree.

[TSH110 in reply to humanbean]

Oh yes the menopause and depression I was told that that was my problem for years, that stupid old rubbish they are still trotting out because they are too lazy to investigate further - easy, cheap option every time and ignore or belittle what the patient tells them. Years of suffering because of those Tom fools, they can’t give me back all those lost years thanks to their incompetence. Why oh why are they still persisting in pushing that nonsense -the get out clause to do nothing ?

[TSH110 in reply to humanbean]

HRT made it a bit less awful for a while anyway….but I probably never needed hrt if the hypothyroidism had been addressed in a timely manner

[arTistapple in reply to humanbean]

humanbean, you do rather get to the point don’t you? And dare I say with humour or at least dark humour. Keep at it.

[humanbean in reply to arTistapple]

you do rather get to the point don’t you?

If you ever read some of my older posts, from say five years ago or before, you'll find out I used to waffle a lot, and would write the occasional novella as a reply. I try to keep it more succinct these days.

[arTistapple in reply to humanbean]

Totally get it. It’s where I am now. It’s because a platform is finally available I am sure. I will get better at it!

[annabianca]

Big pharma is working on slow release LT3, so now patients need combination LT4+LT3 therapy. This is going to be more expensive than plain levothyroxine.

Doctors in some countries (for example Italy and the US) are already pushing for more expensive types of levothyroxine such as Tirosint, claiming that it is purer and you can drink coffee after 30 minutes instead of waiting a whole hour!