Levothyroxine Monotherapy and Cancer

[jimh111]

Whilst our attention has been on COVID-19 recent research has shown that T4 proliferates cancer by acting on the "integrin αvβ3 receptor", a receptor on the cell membrane. At physiological levels T4 (and not T3) is the active hormone.

Research outcomes are complex but on balance high T4 levels are more carcinogenic than low T4. Studies indicate that levothyroxine monotherapy is associated with increased cancer cases and mortality rates.

This is a sensitive and complex issue which I feel needs to be addressed urgently. I have put a full description along with the evidence here: ibshypo.com/index.php/thyro... with an attempt to estimate the number of deaths resulting from monotherapy as compared to combination therapy.

I have always been in favour of using levothyroxine when it works for the patient, usually in simple cases of primary hypothyroidism. In the light of recent research, I feel levothyroxine / liothyronine combination therapy should now be the usual treatment for primary hypothyroidism. A relatively small amount of liothyronine would avoid having above average fT4 levels as well as giving symptomatic improvement for some patients.

The levothyroxine Patient Information Leaflet (PIL) should include a warning to consult your doctor if you are taking levothyroxine and have cancer. This will enable the oncologist to consider on a case-by-case basis whether thyroid hormone treatment needs to change.

As most of you are aware I am a patient, not a doctor.

[smilingjane]

Thanks for passing that on Jimh111

[amala57]

Thank you.

[jgelliss]

Thank You so much jimh111 for this post. It's a very big eye opener for me and I'm sure many many who are on high doses of T4 sole. I know that many especially after TT and those that have thyroid ailments welcome having some T3 mix with their T4 . I would love to know if there are any studies on those that are on T3 sole?

[jimh111 in reply to jgelliss]

I don't know of any studies on T3 only therapy. The 'combination' studies mostly look at those who have taken any T3, they don't on the whole look at the mix. I guess there are too few patients on T3 only to do a study (they need to look at 1,000s over years to get a statistical result).

[jgelliss in reply to jimh111]

Thank you . It would be interesting. Just a thought.

[humanbean in reply to jimh111]

This is not a research paper, it is a case report on a woman who gave birth twice while on T3 only, but it might be of interest :

endocrine-abstracts.org/ea/...

[jimh111 in reply to humanbean]

I was thinking specifically of T3 only therapy and cancer. However, this case report illustrates a general problem, the lack of scientific method in endocrinology. With cancer we might intuitively expect T3 therapy to lead to more cases and mortality on the basis that the body would be less able to protect itself via deiodinase mechanisms. In reality, the integrin αvβ3 receptor is discovered and in reality T4 is more deadly. We have to follow the evidence, not the hypothesis.

In the case of T3 we might intuitively expect mothers on T3 therapy to give birth to cretins on the basis that the transfer of T3 across the placenta (in rodents) is reduced by type-3 deiodinase. Again, the evidence does not follow the hypothesis, both babies were fine and their intelligence slightly above average for their age.

The dogma against T3 in pregnancy is so entrenched that most guidelines strictly 'forbid' it. The endocrinologists, in collective stupidity, forget that most hypothyroid mothers have been treated with T3 (in NDT) for over a hundred years. Indeed, by simple arithmetic we can deduce that some of these anti-T3 endocrinologists were born to mothers who were on T3 therapy!

[dtate2016 in reply to jimh111]

"We have to follow the evidence and not the hypothesis" Bravo!

Thank you for bringing the evidence to our attention. And yes, there is a reason NDT has been around for over 100 years. Simply, it works. Finding the correct dosage is the only question to how well it works. Over dose is easy in my experience. Hence, we continue to hear on HealthUnlocked and other places: "Low and slow". Sage advice.

[Delgor]

As you rightly said Jim this is a sensitive and complex issue and it's good to hear your findings but this wouldn't explain the reason I had breast cancer which followed on from my going very overactive after a virus and having a thyroidectomy. All of this happened before I ever started taking any thyroid medication which as it happens was NDT but I feel convinced that my thyroid issue played a big part in my getting the bc.

[jimh111 in reply to Delgor]

Breast cancer is a special case as I note on the website. In some breast cancers that are sensitive to oestrogen levels thyroid hormone is ‘oestrogenic’ and so increases the risk. I’m not up on this but what I’m trying to say is excess thyroid hormone increases the risk of breast cancer.

The risk is increased but you can’t be sure an individual case was caused by excess hormone. I draw attention to the special case of breast cancer on the website because we can’t draw conclusions about the role of the integrin αvβ3 receptor from breast cancer studies.

[Delgor in reply to jimh111]

Thanks so much for that - I keep on learning and learning and thank you for your patience as I try to get my head around everything.

[jimh111 in reply to Delgor]

You're welcome. I don't have any cancer knowledge, I've been looking at the role of the receptor and the numbers.

[Buzcat in reply to Delgor]

I had been on Levothyroxine for 30yrs mostly the same brand was switched to another brand and my health went right down went three time to a GP she kept saying it’s your age one of the symptoms I got was pain in my left breast it went to nearly double the size of the right got heart issues as well and went on to have a heart attack the only medication I was on was Levothyroxine and was very fit and active before this change but it has all been covered up they have said now new guidelines have been put out but any pharmacy I ask about the guidelines they say they know nothing about it and even if the GP writes the brand on your prescription the pharmacy will say they have to take what they get in the one that gave me all the trouble was already withdrawn before but it was put back out in 2016 the endocrinologist said it was a stronger one.

[jimh111 in reply to Buzcat]

It's always difficult to know if a medication causes a problem, we can only look at the statistical odds. Certainly some patients report problems with levothyroxine, especially heart problems. This surprises me but we should observe what actually happens to patients not go by our assumptions. One of the reasons why I looked into levothyroxine monotherapy and cancer is to show liothronine used carefully is at least as safe as levothyroxine and there is some evidence to show it is safer.

The guidelines are for the doctor not the pharmacy. If your doctor specifies a specific brand the pharmacist should dispense that brand. If they don't you could ask for the prescription back and go elsewhere. The pharmacy doesn't have to take what they can get, the take the cheapest to make a bigger profit. If you have a choice of pharmacies I would tell them clearly that no other brand will do and go elsewhere if they are not prepared to dispense it. They are just trying to bully you because they are lazy. If there are no other pharmacies nearby you could consider using one of the online pharmacies.

[Buzcat in reply to jimh111]

My daughter was also given this new formulation brand and she had the same symptoms as myself so we know it was the change of brand yes pharmacy’s get the cheaper brands in but in the long run it’s costing the NHS a lot more as both of us had to go to AandE on a few occasions I have went to a lot of pharmacy’s and asked if they could get my brand but it seems money is more important than peoples health one even said it doesn’t matter because the manufacturers name that’s on the box could be different to what’s on the leaflet inside so what chance do you have.

[jimh111 in reply to Buzcat]

What brand are you trying to get? If the doctor specifies a brand the pharmacist should dispense it. The name on the box (brand) is linked to the product licence which specifies the actual tablet. As long as the licence number matches it's the same.

[Buzcat in reply to jimh111]

The GP writes the brand but it makes no difference it’s Mercury pharma

[helvella Administrator in reply to Buzcat]

Hope this might help. What make do you get written on your prescriptions?

Prescribing Levothyroxine by Brand

Levothyroxine: new prescribing advice for patients who experience symptoms on switching between different levothyroxine products

If a patient reports persistent symptoms when switching between different levothyroxine tablet formulations, consider consistently prescribing a specific product known to be well tolerated by the patient. If symptoms or poor control of thyroid function persist (despite adhering to a specific product), consider prescribing levothyroxine in an oral solution formulation.

Advice for healthcare professionals:

• generic prescribing of levothyroxine remains appropriate for the majority of patients and the licensing of these generic products is supported by bioequivalence testing

• a small proportion of patients treated with levothyroxine report symptoms, often consistent with thyroid dysfunction, when their levothyroxine tablets are changed to a different product – these cases are noted in UK professional guidelines

• if a patient reports symptoms after changing their levothyroxine product, consider testing thyroid function

• if a patient is persistently symptomatic after switching levothyroxine products, whether they are biochemically euthyroid or have evidence of abnormal thyroid function, consider consistently prescribing a specific levothyroxine product known to be well tolerated by the patient

• if symptoms or poor control of thyroid function persist despite adhering to a specific product, consider prescribing levothyroxine in an oral solution formulation

• report suspected adverse reactions to levothyroxine medicines, including symptoms after switching products, to the Yellow Card scheme

Above is directly quoted from link – where there is also further information:

gov.uk/drug-safety-update/l... for-patients-who-experience-symptoms-on-switching-between-different- levothyroxine-products

The above is in my Vade Mecum document.

helvella - Vade Mecum for Thyroid

The term vade mecum means:

1. A referential book such as a handbook or manual.

2. A useful object, constantly carried on one’s person.

Please don't get put off by the number of pages!

Not everything is in this one document - my major medicines document is still separate!

From Dropbox:

dropbox.com/s/vp5ct1cwc03bl...

From Google Drive:

drive.google.com/file/d/1ZW...

[Buzcat in reply to helvella]

Yes I do know about this but it’s not being adhered to by pharmacy’s well not in some parts of Glasgow .

[helvella Administrator in reply to Buzcat]

In which case, put in a complaint. Scotland has a different NHS structure, so I do not know where you need to address that complaint. But even a complaint to the company that runs the pharmacy should get an answer. If they say they can't help, escalate and escalate again.

[jimh111 in reply to helvella]

… and if you don’t get any satisfaction take a photo of yourself outside the pharmacy looking very sad and send it to the local paper.

[jimh111 in reply to Buzcat]

This previous post may be helpful healthunlocked.com/thyroidu... . I think you just need to put your foot down and make it clear you won’t accept anything else.

[Delgor in reply to Buzcat]

Hi Buzcat, I am assuming that you meant to write to Jim and not myself and so I am pleased he replied giving you the advice you needed with respect to having the same brand of levothyroxine from your pharmacy. This is a great forum for so many people with thyroid issues who don't get the care they really need from either GP's or Endocrinologists who in the main don't know enough about the subject. I've learnt so much from the kind and knowledgeable people on here and hope it will be the same for you!

[Delgor]

👍

[wellness1]

Thank you for putting this together, jimh111.

[Bearo]

Thanks for posting. At dx myFT4 was below range, although I didn’t feel particularly unwell. Now, on Levo mono therapy, My FT4 is slightly over range and my FT3 is high in range. I kept wondering if I should reduce my dose a little, especially as I don’t suffer many hypo symptoms, feeling ok whatever the dose. Now, maybe I have a reason to take a bit less Levo. I’ve already had breast cancer (before hypo dx - but maybe they were linked).

[jimh111 in reply to Bearo]

I try to stay on the lowest effective dose as like you I am on highish levels. I did this before I knew anything about a cancer link. The studies show risk so it just alters the odds, there's no guarantee. Of course of we need to take enough hormone to have a decent life.

[dtate2016]

Why are we not surprised? Thanks for the info. I was forced to stop taking Levo over a year ago. It’s been a liberating journey! (And after 30 years more than a little bit apprehensive). This information helps me to be glad I listen to my body and some new information on iodine overload. When I do you need to take just a minuscule amount I take T3. Always enjoy your posts!

[jimh111 in reply to dtate2016]

Thanks for the nice comments. I always felt levothyroxine monotherapy was fine for people who do well on it but recent evidence indicates it is harmful and so I now believe it shouldn't be used on most patients.

[Bearo in reply to jimh111]

I’ve always worried I don’t need to be on it at all! Two or three years ago I was given Levo for a TSH of 4.9 and FT4 one below the range. I also had very low vit D and low ish B12. But I didn’t really have many hypo symptoms, if any. I’m now on 100mcg Levo and feel fine on it although slightly over range FT4 and high in range FT3, plus TSH of 0.1 is leading me to skip a pill once a week to improve this numbers a bit.

I keep thinking what if I just stop to see where my natural levels are (if they still work!). But I’ve read about people reducing or stopping their dose and really messing up their health; taking ages to get back up to where they felt well.

If only I could discuss this with a health professional who knew anything about it!

[jimh111 in reply to Bearo]

It's difficult because your fT3 wasn't measured when you were first diagnosed. You could have been hypo. or your fT3 could have been reasonable. you could try reducing you levothyroxine dose very gradually. That way you're not taking any risk and you will find out.

[Bearo]

Thanks, Jim, I might try that.

[Alejandrita17]

Hi Jim,

What if You are on monotherapy, have a higher t4 than you had in health, but it is still on range: 1,45 (0,7-1,7)?

Is it dangerous?

I have a lower t3 than in health but feel fine overall.

Would you still consider additional t3?

[jimh111 in reply to Alejandrita17]

This isn't an exact science. The studies show that T4 is linked to cancer whether it comes from the thyroid or from tablets and that high normal fT4 is more of a problem than low normal fT4. Also, levothyroxine monotherapy carries a higher risk than in healthy people. This is most likely because levothyroxine monotherapy generally needs high normal fT4.

As your fT4 is close to midway I wouldn't be concerned especially as you are feeling well. I'd be inclined not to rock the boat. There are risks in everything and as far as I know you are not in a high risk group. Of course I am not a doctor and know nothing about cancer, I've just looked at the odds.

[bluebell99]

Thank you for your information jimh111 . I am a survivor of kidney cancer and have been taking levo for many years before and since. Not one specialist, oncologist or gp has told me of the high T4 and cancer.

Your work has now made me very aware of the risks, thank you again.

[jimh111 in reply to bluebell99]

Glad to see you survived, I don't know anything about kidney cancer but it must be horrible. There's very little information on kidney cancer and thyroxine, what I've seen tends to be experiments on mice.

Although some of the studies go back for a decade or so most of this research is very recent so I'm not surprised specialists are not aware of it. Also, the balance of evidence has tipped in the last few years, before that it was a possibility not a probability.

I wouldn't blame the specialists, they tend to wait for the science to be reasonably certain before adapting therapies. The important point is that the evidence for this link is now recognised and people should lobby for a change in thyroid therapy.

[dtate2016]

jimh111 - this research is spot on from my experience. I began to have incredible chest pains and the Dr.s only wanted to increase the T4 dosage. I knew it was killing me (heart wise). I had no choice but to begin to experiment with bovine dessicated thyroid glandulars. I found a Dr. who finally listened and I trusted that how I felt was more important. As it turns out, I need very little of it to feel well.

Yes, this is serious information that needs to be examined and heard.

[jimh111 in reply to dtate2016]

Thanks. There are ideas around how T4 interacts with the heart but it is beyond my knowledge and I don't think the experts know either.