I would like to urge any reader to read the entire article and the content of the links prior to considering the implications. The research I am referring to will not apply to everyone on Levothyroxine. Many thyroid patients will do just fine on Levo and never have any issues. So, it is important to put this in that context. Having said that I believe that relevant information needs to be available to thyroid patients so that they can make informed decisions regarding their own health.
This is a very recently published study. The research showed that levothyroxine use was associated with a significantly increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers.
Levothyroxine, also known as T4, and brand names such as Synthroid, is the main medication prescribed by endocrinologists and doctors in the treatment of hypothyroidism. The prevailing endocrinology view is that Levothyroxine always works and that TSH can be used to assess the adequacy of the treatment. There are many research papers that show that these views are flawed. This new paper adds more evidence to this.
This research study was very large and included 601,733 cases of cancer and 2,406,932 controls. So, this was not a small number of people being studied. It needs to be taken very seriously.
The researchers recommend more work to understand the biological reasons for this.
However, it seems obvious to me that at least one of the most likely reasons is that Levothyroxine (T4) often does not result in the same level of FT3 and FT4 that healthy people with a working thyroid gland enjoy. All too frequently, T4 medication results in lower FT3 and higher FT4 in the patient than they had when they were once well. In some cases, this may be due to T4 dosage never being raised to a high enough level because the patient’s doctor thought TSH was too low (see my blogs regarding TSH and the research that examines the flawed use of TSH within thyroid treatment today). In other cases, various issues may have compromised the ability of the patient to convert T4 to T3 as efficiently as they used to (the loss of thyroid tissue can do this, as well as other factors – see my blogs).
Hence, in my view, some of these thyroid patients would be a lot healthier on a mix of T4 and T3 medications, rather than Levothyroxine. So, a combination of synthetic T4 & T3 or a natural desiccated thyroid (NDT) would be healthier for many thyroid patients. The reliance on TSH as the main indicator of thyroid hormone adequacy during treatment also needs to be revised.
As I mentioned in the introduction, this does not mean that all thyroid patients on Levothyroxine have an increased risk of cancer. Some thyroid patients are extremely good converters of T4 to T3 and they will of course have sufficiently good levels of T3 to have no increased risk at all. Those thyroid patients on Levothyroxine and who feel really healthy are also likely to have sufficient T3 and be completely fine also. So, it this is not a blanket issue for all thyroid patients on Levothyroxine.
This research simply points out the risk to some thyroid patients on Levothyroxine. I would think that the people in the higher risk category are those with high levels of FT4, low levels of FT3 and or high levels of reverse T3 (due to poor conversion from T4 to T3), and those that have remaining symptoms of hypothyroidism.
This research provides even more evidence that there is far too much reliance on T4 monotherapy. The faith of doctors and endocrinologists in the effectiveness of Levothyroxine is seriously flawed. Something has to change!
Here is the information on the study that I have so far:
Chieh-Chen Wu, Mohaimenul Islam, Phung Anh Alex Nguyen, Tahmina Nasrin Poly, Ching-Huan Wang, Usman Iqbal, Yu-Chuan Jack Li, Hsuan-Chia Yang. April 2021. Risk of Cancer in Long-Term Levothyroxine Users: Retrospective Population-based Study. Cancer Sci. doi: 10.1111/cas.14908.
When I first posted this I only had the link to the abstract and promised to update this post when the full-text was available:
https://pubmed.ncbi.nlm.nih.gov/33793038/
I now have the link to the full text:
https://onlinelibrary.wiley.com/doi/10.1111/cas.14908
My belief that the increased cancer risk is likely to be connected to the lower levels of T3 generated by Levothyroxine, has further support.
We know from research that dendritic cells play a central role in fighting cancer. These dendritic cells are highly dependent on T3. Research using mice with cancer concluded that T4 therapy showed no increase in the activity of the dendritic cells. However, when the mice were given T3 it helped to destroy the cancers:
https://pubmed.ncbi.nlm.nih.gov/31214123/
Another one of my blog posts that is relevant talks about the risks of high FT4 and rT3. It references a great article by Dr T. S. Smith, that discusses research showing that both the T4 hormone and reverse T3 (rT3) act on receptors on the cell wall called Integrin αvβ3 (or ‘Integrin alpha-v beta-3 receptors’ or ‘Vitronectin receptors’). Through these receptors, T4 and rT3 can cause many types of cancers to grow:
https://paulrobinsonthyroid.com/cancer-scientists-point-finger-at-t4-and-rt3-research/
This piece of research also points out the link between the T4 hormone and cancer – it is referred to in Dr Smith’s article:
https://www.frontiersin.org/articles/10.3389/fendo.2019.00565/full
Here is yet another research article that also links Levothyroxine therapy to increased cancer risk:
https://academic.oup.com/jcem/article/101/12/5030/2765090
Experience of working with thyroid patients also suggests that T4/T3 and T3 treatments tend to cause patients to get far fewer colds, sinus infections, etc. This is anecdotal evidence but it fits well with the idea of Levothyroxine treatment often providing inadequate immune system support.
I hope you found this article interesting and important.
I am also pleased to mention that the paulrobinsonthyroid blog:
https://paulrobinsonthyroid.com/blog/ is now on a list of the Top 10 Hypothyroidism Blogs on the Internet:
https://blog.feedspot.com/hypothyroidism_blogs/
Best wishes,
Paul
Just found your blog. Thanks for sharing your journey. I found the full text link, (so nice it is free to read), for this new research. I will put an ‘x’ in front of the link and another related research article link I’ll share so I don’t get marked as a spammer.
I think you may be fortunate to do well on T3 only.
Risk of cancer in long‐term levothyroxine users: Retrospective population‐based study
xhttps://onlinelibrary.wiley.com/doi/10.1111/cas.14908
Clinical Implications and Impact of Discovery of the Thyroid Hormone Receptor on Integrin αvβ3
xhttps://www.frontiersin.org/articles/10.3389/fendo.2019.00565/full
Thank you so much for the links G.
I will add the full-text link to my blog.
Re: T3 Only, I know of a great many thyroid patients (some who have had TTs), that do very well on T3 Only. The trick is to manage the dosing very carefully. It does require multi-doses and often the doses are of differing sizes and are spaced out differently in time. My Recovering with T3 book describes the protocol that I developed over a ten year period to arrive at effective T3 dosing.
Many thanks once again!
Paul
Very interesting. Since this kind of study is just conducted on healthcare data, I would love to see similar studies conducted for other countries. The paper mentions another study conducted on a Swedish population. https://pubmed.ncbi.nlm.nih.gov/32222650/
It doesn’t look like they don’t separate people taking T4 only and people taking T4+T3. One would think that the vast majority of people are taking T4 only, but we don’t know for sure. The authors didn’t mention T3 use in their list of potential confounders. It might be worth emailing them to ask if they tried including T3 as a confounder and how that affects the results. If they see that levothyroxine is linked to increased cancer risk, but levothyroxine+T3 use is not, that would be quite compelling evidence.
Paul’s hypothesis (which I agree is the most likely one we have) is that there is increased cancer risk because people need to take T3 in addition to T4. However, there is an alternative idea that maybe the levothyroxine itself is causing increased cancer risk. This seems unlikely because levothyroxine is bioidentical, but maybe it knocks the body out of homeostasis or something. Doctors that believe in this hypothesis might become even more reluctant to treat subclinical or mild cases of hypothyroidism. I hope this does not happen, since I think Paul’s hypothesis is significantly more likely to be right, and it is hard enough to get treatment for subclinical hypothyroidism already.
Hi Jay, thanks for your comments. One of the papers referred to within my blog post is by Aleck Hercbergs and he is convinced it is the T4 itself (when it is high) that is the problem. Of course in good converters of T4, the T4 level is usually not high as it goes to a healthy amount of T3. So, I believe the risk category is really those patients who are poor converters and who have had their T4 dosage raised to a high level in an attempt to eradicate symptoms. A T4 / T3 approach for these people would be far safer. This is my interpretation.
Here is the Hercbergs article again where he discusses the research: https://www.frontiersin.org/articles/10.3389/fendo.2019.00565/full
Thanks once again, Paul
Thanks for bringing light to this new information. What is considered “high FT4”?
Good question.
I think I would be concerned with very high in the range FT4 that was not converting to good levels of FT3.
Reverse T3 that was high in the range would also be a marker that the body was trying to clear excess T4.
People who convert T4 well often have mid to high in the range FT3 with only mid-range FT4 – because the T4 is being converted so well.
More than the above, if you feel fantastic and have no hypothyroid symptoms at all, and you have normal body temperature and other signs like BP, cholesterol etc. then you likely have very little to be concerned about.
This information is more to do with the thyroid patient on T4 based meds who still suffers from hypothyroid symptoms and is not converting T4 to T3 very efficiently.
Hope this helps Scout.
Best wishes, Paul
Thanks for replying. My last t4 test was a while ago in 2014 but it was 1.53 on a range of .89 to 1.76. I had been on levothyroxine for 4 years at that point.
I had my left lobe removed in 2010 and they found a microscopic follicular carcinoma but left my right lobe intact. They tried to let me go without any Synthroid but over the coming months post-surgery my TSH climbed to a high of 8 so they put me on levothyroxine. My latest TSH was 1.4. My thyroglobulin was 12 ng/l at the same visit just two weeks ago. I would be interested in your thoughts.
Thank you for your time!
My thoughts are that they need to be tracking Free T3. T3 is the active hormone.
Only FT3 improvement improves symptoms – TSH level and FT4 level are not correlated to symptoms:
https://paulrobinsonthyroid.com/only-free-t3-ft3-tracks-changes-in-symptoms-during-thyroid-treatment-research/
Best wishes, Paul