Levothyroxine causing cancer

[Soaping]

I have just received email from Dr Westin Childs regarding research from Tywain into levothyroxine causing cancer to over 50% of people who take levothyroxine and it has really worried me 😪

[RedApple Administrator]

Soaping, can you provide a link to this information so that others can read and understand what you're referring to? Simply saying levothyroxine causes cancer is going to scare many members, so some context is needed.

I recall jimh111 has discussed the issue of levothyroxine and cancer on this forum, so hopefully he will pop by and comment here.

[Soaping in reply to RedApple]

Hello RedApple, Sorry if ive worried people i got freaked out about the article think this is the link restartmed.com/does-levothy... its more to do with getting t3 and t4 in balance which is difficult for some of us.

[Lalatoot]

Here is the post  RedApple

healthunlocked.com/thyroidu...

This is a previous discussion about levo mono therapy cancer risks and ft4 levels.

[LucyYoga]

If you read the article you will see is is not saying levo itself causes cancer but it is more likely due to the under medication that is associated with T4 mono therapy

[helvella Administrator Thyroid UK]

When it comes to important studies, and this might be one, there is no substitute for the actual paper itself.

Thankfully, this one is open access:

Risk of cancer in long-term levothyroxine users: Retrospective population-based study

Chieh-Chen Wu, Md. Mohaimenul Islam, Phung-Anh Nguyen, Tahmina Nasrin Poly, Ching-Huan Wang, Usman Iqbal, Yu-Chuan (Jack) Li, Hsuan-Chia Yang

First published: 01 April 2021

doi.org/10.1111/cas.14908

Abstract

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case-control study was conducted using Taiwan’s Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first-time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46-1.54; P < .0001) compared with non–users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48-2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17-1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01-1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15-1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients’ condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.

onlinelibrary.wiley.com/doi...

I'll add a few fragmentary comments:

This paper is not brand new - it is already two years since publication. I suspect it has already been commented on here but the search facility is too poor to be sure of finding it. (And not everyone will include authors, etc. which help a lot in searching.)

Indeed, I myself posted about a previous paper about five years ago, on the same subject area, from the same lead author:

healthunlocked.com/thyroidu...

It is very difficult to separate the direct effects of levothyroxine from those of being hypothyroid then under- and/or over-dosed for years.

So many who are hypothyroid have histories of taking multiple other medicines - before and after diagnosis.

We really do not have a comparable group who took anything else! It might be possible to compare against those who take desiccated thyroid in the USA. Even then, many will have taken levothyroxine for years.

The final conclusion paragraph is very, very cautious and has obviously been deeply considered:

In conclusion, our study findings showed that levothyroxine use is associated with increased risk of cancer and should be taken into consideration in initiating and renewing levothyroxine therapy for patients with hypothyroidism. However, the findings of the current study should be interpreted with caution. We have to emphasize that this case-control study describes associations and not causal relationships between levothyroxine and cancer risks. Therefore, levothyroxine is still considered an effective medication, and the current study does not advise against use of this medication. The results of the current study could serve as a reference for interested researchers to conduct further research, and more in-vivo studies and meta-analyses are required to examine the causality and to identify the mechanisms of these associations.

[radd]

Soaping,

All hormones have to do the job they are designed for to not only maintain well-being but prevent unwanted side effects from unutilised hormone which the body sees as excess. There are many reasons why hormones may be prevented from doing their job (eg nutrient deficiencies, excess transporters, poor cellular function, chronic inflammation, the list is endless!)

A tiny bit of unused hormones is peed out and the rest of the excess is regulated by activation/deactivation enzymes to control thyroid levels at both tissue and temporal level. These inactivated metabolites in the right proportions are useful but when we have excess thyroid hormone long term it can bring unwanted side effects and this is where as I understand it the cancer risk comes in by turning on certain genes. 

Therefore, by ensuring our meds are working correctly, staying within thyroid hormones ranges (but not TSH) and aiming for best FT3/FT4 ratios as opposed to raising levels as high as possible all help reduce this risk which is only a risk in people more susceptible.  

[SlowDragon Administrator]

Being larger/overweight will increase risks of cancer

Obviously many thyroid patients struggle to loose weight

cdc.gov/cancer/obesity/inde...

HRT possibly increases risk of cancer

cancerresearchuk.org/about-...

[Soaping in reply to SlowDragon]

Hello SlowDragon, when your struggling to get your t3 up the last thing you want is emails telling you this information which has got me worrying, i think i will unsubscribe to Dr Westin Childs . Sorry everyone 😮‍💨xx

[radd in reply to SlowDragon]

SD,

I've been listening to podcasts lately so can't offer links to a paper atm but I understood the latest research showed body identical HRT to actually reduce breast cancer risk, ie numbers of women on HRT getting breast cancer has shrunk by an unprecedented amount. I picked up on this information because of its irony given the awful implications of the early HRT's.

maybe others will comment and I'll do some more investigating later.

[SarahJane1471 in reply to radd]

you are correct. It’s the OLD types of HRT that have risks. I did all my research about this before I went on body identical HRT

[Brightness14]

I you read the full text he thinks that it is because the patients are hypothyroid and not dosaged properly. That is the reason for the Cancer not that they are on Levo itself.

[jimh111]

I've had a chance to look at Dr Childs' article and the paper he references. it appears that he has seen this paper and makes reasonable comments on it. Unfortunately, this is one of the few papers on the subject that do not mention that the link is with thyroxine rather than specificially levothyroxine therapy. Nor does it cite the evidence that this association is caused by the effect of thyroxine (and reverse T3) at the integrin αvβ3 receptor.

The primary action of thyroid hormone is by T3 on nuclear receptors 'thyroid hormone receptors'. This is known as 'genomic action' and it controls things like metabolism and development. Thyroid hormones can also have non-genomic actions, they have effects that are not linked to T3 binding to nuclear receptors. One of these is the 'integrin αvβ3 receptor' on the cell membrane. T4 (not T3) binds to this receptor and it is this action that promotes cancer. Higher levels of T4 (natural or from levothyroxine) are associated with cancer progression in multiple ways.

In my T4 and cancer topic ibshypo.com/index.php/thyro... I describe some of the studies in this area. Cancer itself can play havoc with thyroid hormones so it was cruical to select studies that looked at T4 levels a few years before the onset of cancer. It's possible that these studies somewhat underestimate the risk because it's possible that higher or lower levels of T4 were subsequently 'corrected', at least for those on levothyroxine.

Dr Childs raises the question of confounding factors such as a persons weight or smoking status but the studies I've seen use the standard technique of doing a multivariate analysis or correction. Factors that may bias the results are taken into account during the analysis.

The hypothesis that the cancer may be caused by giving the patients too little levothyroxine is wrong, the studies link the cancer risk to levothyroxine dose and duration. That's not to say patients should be undermedicated, rather they should receive some T3 to reduce their cancer risk and facilitate clinical euthyroidism.

It's true that the studies are retrospective, this is quite usual for large scale (millions of subjects) cancer studies. There was one intervention study academic.oup.com/oncolo/art... which had very striking results, it needs to be backed up with further studies.

I used to advocate levothyroxine monotherapy for people who did well on it. Given the link between higher normal T4 levels and cancer I now feel that levothyroxine monotherapy should not be routinely used.

I raised these issues in a response to the proposed NICE guidelines on treating thyroid cancer. It seems daft to suppress TSH in cancer patients with T4 levels that are known to promote cancer. I had a small success in that the original recommendation to 'treat with levothyroxine' was changed to 'treat with thyroid hormone'. They have left the door open for alternative therapies.

The BTF recently had a talk on thyroid cancer, I sent them a question in advance and they said it would be addressed. It wasn't covered in the talk but might get an answer when they publish the video and follow-up submitted questions.

It's a difficult question but I'm getting the impression that endocrinologists are ducking the question because they don't like the potential ramifications. Don't worry about killing people, just keep our life simple.

One study found that people with an fT4 in the lower tertile lived three and a half years longer than those with higher fT4. When treating hypothyroid patients we have the choice of what fT4 to target and potentially save tens of thousands of lives. Contrast this with the latest paranoia around cough medicines which may cause exceedingly rare problems chroniclelive.co.uk/news/he... .

Most of you will know I am not a doctor and I have no special knowledge of cancer.

[Regenallotment in reply to jimh111]

great work jimh111 thank you for the time you invest on all out behalf’s. Brilliant you influenced the NICE outcomes 🤜

[fifi6]

After reading this information and not really fully understanding I am now considering coming off levothyroxine as I’m already at higher risk of breast cancer from family genes. Are there any natural supplements/diets that have been shown to work and help?

[Regenallotment in reply to fifi6]

Why not look at combining low dose T3? NDT? Thyroid glandulars? We have combination options. Coming off Levo without alternatives can make you very unwell, absolutely not recommended.

[helvella Administrator Thyroid UK in reply to fifi6]

We have had many posts/replies from people who stopped levothyroxine for various reasons over the years.

Some suffered severely from doing so - and took months or years to recover from their experiment. (Though quite a few were taken off by doctors or circumstances rather than by choice.)

If your body cannot make sufficient thyroid hormone, the only answer we have is to take supplementary thyroid hormones. The discussion is whether that is levothyroxine, liothyronine, desiccated thyroid or a combination - and the dosing. There is no supplement (natural or otherwise) that can replace thyroid hormone.

Any supplement that had an impact on your need for thyroid hormone might work due to an impact on helping ensure FT4 remains at the same level despite a lower dose. Thus would likely do absolutely nothing to reduce any risk.

As jimh111 clearly states, it isn't taking levothyroxine, it is the level of levothyroxine (and includes any T4 you might still be making yourself), and only at the higher end (high or over-range FT4).

Quitting levothyroxine is likely to almost immediately cause multiple issues.

[jimh111 in reply to fifi6]

The studies show that higher fT4 within the reference interval (and above the upper limit) carry higher risks. Having an fT4 in the lower part of the reference interval is fine although thyroid patients may need a little T3 to be euthyroid. It's not T4 that is the risk but the amount of T4, a bit like good and bad levels of cholesterol.

In the general population about a third are lucky in that they have the lower normal fT4 levels associated with a longer life, just one of many genetic chances. My view is that for hypothyroid patients there is a choice of whether to give them a high normal fT4 with levothyroxine monotherapy or to add in a little T3 to allow a lower fT4. It makes sense to target the safer hormone profile. The standard approach in medicine is to aim for a healthy target, as far as it is achievable.

T4 is not bad but higher levels are associated with risk.

[fifi6 in reply to jimh111]

Thank you for your comments. I am on 100 levothyroxine and 10 liothyronine at the moment. My TSH us 0.05 (0.27 -4.20) Free T4 level 18.1 (12.00 - 22.00) what would you suggest for me to do to have the correct levels please? My endocrinologist really doesn’t seem to worry as long as they see everything in range..

[jimh111 in reply to fifi6]

'correct levels' isn't really the thing to aim for. Obviously the important factor is to be well enough to function reasonably well. You have a low TSH and ideally it would be higher. You could try reducing your levothyroxine slightly and this might bring your fT4 down and TSH up - provided it doesn't make you worse. I'm thinking in terms of a small adjustment like taking 50 mcg a couple of days a week without having to get your prescription changed, at least not until you are sure you are OK.

We can't always have ideal hormone levels and be well, that's the problem with having an illness. So, we can try aiming for 'ideal' levels but may have to compromise.