Thyroid Hormone Levels and Your Genes

The genes involved in hypothyroidism and Grave's.
The genes involved in hypothyroidism and hyperthyroidism.

Thyroid hormones are often in the news these days with more and more people recognizing the importance of the thyroid in so many functions in the body.  In 2014, the #1 prescribed drug in the US  was Synthroid, a synthetic thyroid hormone.[ref]

Many articles that I’ve read online focus on the lifestyle factors of thyroid hormone issues and never mention genetic variability. This post will dig into the genes involved in thyroid hormone production and conversion.

A good source of background information on all things thyroid is the website (and book) Stop the Thyroid Madness.  If you are unfamiliar with the ins- and-outs of thyroid hormones, I recommend that you start there first.

A quick overview (for those unfamiliar with thyroid):  thyroid hormones affect every cell in the body and control many functions such as metabolism, heart rate, body temperature, muscle contractions, and digestive functions.  The thyroid gland is located in the neck and uses iodine to create the thyroid hormones thyroxine(T4) and triiodothyronine(T3).  The rate at which the thyroid gland produces and releases thyroid hormone is controlled by the hypothalamus and the pituitary gland through thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH).

Signs of Hypothyroidism  (Wikimedia Commons)
Signs of Hypothyroidism (Wikimedia Commons)

Hypothyroidism is caused by too little thyroid hormone; hyperthyroidism is caused by too much thyroid hormone.  T3 is the active form of thyroid.  The thyroid gland produces and releases much more T4 than T3 (around 90% more), but enzymes can convert T4 to T3 in your tissues and organs.  Too much of the active T3 in cells will cause enzymes to inactivate it to reverse T3.

So you can see that thyroid hormone levels are an intricate balance between production of T4, conversion to T3, inactivation to rT3, TSH levels, and the feedback loops controlling TRH and TSH. So in addition to diet and environmental toxins, genetics can play a role at many points along the way.

Recent Studies on Thyroid levels:

According to thyroid.org, 20 million Americans currently have a thyroid disorder with even more at risk of sub-clinical hypothyroid disorders.  Why now?

I’m sure there are many reasons for the increase in hypothyroidism such as foods that we are eating and the fact that we no longer eat the thyroid glands of animals. The recently popular ketogenic (Adkins) diet may also play a small role.  But I hadn’t considered the ubiquitous role of chemicals that are found in nearly everyone’s bloodstream such as PFOA’s, BPA and phthalates until I came across several recent studies showing a relationship between thyroid hormone levels and environmental toxins.  Study results include:

  • PFAS (Perfluoroalkyl substances in cleaners, insecticides, flame retardants, carpet and fabric stain repellant, and food packaging) affect TSH levels [study]
  • BPA and phthalates (in plastics and register receipts) affect thyroid levels.[study]
  • Triclosan (previously used in antibacterial soaps) affects T3 and T4 levels as well as other markers. [study]
  • Depending on your DIO2 genes, organochlorides (in pesticides) may make a significant difference in your thyroid levels.[study]
  • Sucralose (splenda) also alters thyroid hormone levels by increasing rT3 (rat study) [study]

T4 deiodinated to T3DIO1, DIO2T4 deactivated to rT3T3 converted to T2DIO3Genetics  of thyroid hormone levels:
A person can be naturally slightly higher or lower than the average for TSH levels based on their genes.   An interesting study published in the journal of the European Society of Endocrinology looked at the heritability of thyroid hormone levels in men who had no thyroid auto-immune disease or dysfunction and found several SNPs that were responsible for approximately 50 – 90% of thyroid hormone variability.

TSHR – Thyroid stimulating hormone receptor (TSHR) gene:

“The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism.” [ref]

TSH (thyroid stimulating hormone) levels are also tied to genetic variations.  TSH levels are often the first thing that a doctor will check in regards to thyroid function, although some argue that TSH is not very useful in diagnosing hypothyroidism.

Check your 23andMe results for rs1991517:

  • CC: normal
  • GG: slightly lower average TSH [ref]

The PDE8B gene polymorphism is associated with TSH levels, specifically in those of European descent.[ref]  There are quite a few studies on this gene; a search in PubMed will give you more information.

Check your 23andMe results for rs4704397:

  • AA: increase of 0.26 uIU/ml in serum TSH [ref]
  • AG: increase of 0.13 uIU/ml in serum TSH
  • GG: no increase in serum TSH

 

The FOXE1 gene (thyroid specific forkhead transcription factor) has also been identified to increase the risk of primary hypothyroidism. [ref]

Check your 23andMe results for rs7850258:

  • AA: Lower odds of hypothyroidism (OR = 0.74)  [ref]
  • AG: Typical odds of hypothyroidism
  • GG: Slightly higher odds of hypothyroidism

 

Check your 23andMe results for rs965513 :

  • AA: decreased TSH, increased risk of thyroid cancer   [ref]
  • AG: decreased TSH
  • GG: normal

 

AutoImmune – Grave’s and Hashimoto’s

A 2012 study published in the Endocrine Journal showed that there are several SNPs in the TSHR gene that influence the risk of the autoimmune thyroid diseases (AITD), which includes Graves’ disease and Hashimoto’s thyroiditis.  The study states that “genetic factors confer 80% contribution to the etiology of AITD”.[ref]  Note that this does not mean that 80% of people with the SNPs have Graves’ or Hashimoto’s.  The prevalence of Hashimoto’s in Caucasian women is between 1 and 2% and is even less in men.[ref]

Check your 23andMe results for rs3783938:

  • TT: higher frequency of Hashimoto’s (OR 1.4)
  • CT: higher frequency of Hashimoto’s
  • CC: normal

 

Check your 23andMe results for rs12101255:

  • TT: higher frequency of Graves’ disease (OR 1.4 – 1.8) [ref]
  • CT: higher frequency of Graves’ disease
  • CC: normal

 

Check your 23andMe results for rs179247:

  • AA: increased risk of Graves’ disease (OR 1.4 – 1.8) [ref]
  • GG: normal

 

DIO1, DIO2 – Deiodinase genes for conversion of storage (T4) to active (T3)

The deiodinase 1 (DIO1) gene encodes a protein that converts T4 to T3 and is involved in the degradation of both T3 and T4.  Iodine and selenium are involved in these reactions.  [ref]  DIO2 is also involved in the conversion of T4 to T3.

Check your 23andMe results for rs2235544:

  • AA: decrease ratio of fT3 to fT4, decreased free T3  [ref]
  • CC: increased free T3 and decreased free T4

 

Check your 23andMe results for rs11206244:

  • TT: higher rT3, lower free T3  [ref]
  • CT: lower T3
  • CC: normal

 

Check your 23andMe results for rs225014: [snpedia]

  • CC: decreased DIO2 enzyme (T4 to T3 conversion)  [ref]
  • CT: decreased T4 to T3 conversion
  • TT: normal DIO2 enzyme

So why would these deiodinase polymorphisms be important?  The most common prescription for hypothyroidism is Synthroid, which is T4 only.  One reason for not doing well with Synthroid could be that the T4 is not being converted properly to T3 by the deiodinase enzymes.

Thyroid Hormone Receptors  (THRB, THRA)

Check your 23andMe results for rs28933408: [snpedia]

  • TT: thyroid hormone resistance  [ref]
  • GG: normal


Promoting Thyroid Health:

  • Selenium is essential to the conversion of T4 to T3.  Brazil nuts are a good source of selenium, and supplements are also available.
  • The dietary flavonoid kaempferol, found in apples, onions, leeks, grapes, and other fruits and vegetables, induces DIO2 increasing conversion to T3. [study]
  • There are thyroid glandular supplements (dried thyroid gland) which may — or may not — increase thyroid hormones. It is interesting to note that people historically ate most parts of animals including the thyroid gland.  Sweetbreads are the thyroid glands of calves or lambs.
  • Gluten is often pointed to as a culprit in autoimmune thyroid diseases (Graves and Hashimoto’s).  A 2003 study showed that ~5% of patients with autoimmune thyroiditis also had immune reactions to gluten.[study]  While that isn’t a huge percentage, it may be worth trialing a gluten-free diet if you have an autoimmune thyroid disease.
  • In studies, fasting and critical illnesses increase the levels of DIO3, which is the enzyme that deactivates thyroid hormone.[study]  Avoiding fasting (and illness!) should thus be better for thyroid hormone supply.
  • Light and circadian rhythms play a role in DIO3 expression as well.[study]
  • Several recent studies have also pointed to the hereditary epigenetic effects on DIO3 as well.  [study]
  • For autoimmune thyroid problems, myo-inositol and selenium have been shown to reduce antibody levels. [study]
  • Vitamin D supplement has been shown to reduce Hashimoto’s antibody levels. [study]  This is the one that I use that has coconut oil instead of soybean oil.  (Not saying that anyone should by the brand because I use it — rather that you should make sure that read the ingredients so that you don’t end up with soybean oil or cottonseed oil.)

More to read:
I encourage everyone who has thyroid problems to read and research more on this issue.  There is a lot more information out there!

Updated 4/2017

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Comments 4

  • Remarkable things here. I’m very glad to look your post.
    Thank you so much and I’m taking a look ahead to contact you.
    Will you please drop me a mail?

  • I was wondering if you ever considered changing the layout of your website?
    Its very well written; I love what youve got to say. But maybe you
    could a little more in the way of content so people could connect with it better.

    Youve got an awful lot of text for only having 1 or 2 pictures.
    Maybe you could space it out better?

  • Love this info, but I think you have 1 or 2 typos in the SNPs’ I believe the deiodinase 1 (DIO1) gene’s SNP starts with “rs” no “rrs”. And the first SNP listed yielded a C/C for me, which should be an impossible base combo if the variants are all A and G.

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