The thyroid is a master regulator of many of your body’s systems. It is integrally involved in metabolism and helps maintain body temperature, heart rate, breathing, and body weight. The thyroid is a butterfly-shaped gland that is located at the front of your throat (right below the Adam’s apple for men). [ref]
Your genes play a big role in how well your thyroid works and how your body produces and converts the different forms of thyroid hormone.
More people than ever are having problems with low thyroid levels. In 2016, the #1 prescribed drug in the US was Synthroid, a synthetic thyroid hormone with 123 million people on the drug.[ref] Thyroid hormone levels play a vital role in how you feel and in your overall good health.
If you have thyroid problems, learning which genetic variants you carry may be a way to shed some light on what is going on with your thyroid. Knowing where your genetic susceptibilities are can lead to figuring out (with your doctor) the best way to solve the problem. YOU are your own best advocate. I encourage you to learn everything you can about your thyroid health.
Background on the thyroid gland:
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).
Hypothyroidism is caused by too little thyroid hormone; hyperthyroidism is caused by too much thyroid hormone.
The active form of thyroid hormone that your body uses is T3. 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 (rT3).
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. In addition to diet and environmental toxins, genetics can play a role at many points along the way.
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.
Genetics of thyroid hormone levels:
The first thing that most doctors check on a blood test is the TSH (thyroid stimulating hormone) level. A person can be naturally slightly higher or lower than 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. Thus TSH levels naturally vary a bit from person to person.
Thyroid stimulating hormone receptor (TSHR) gene codes for a receptor protein that controls thyroid cell metabolism. [ref] TSH (thyroid stimulating hormone) levels are also tied to genetic variations of the TSHR gene. Grave’s disease is an autoimmune condition that affects about 1% of the population. In Graves’ disease, the body produces antibodies against TSHR. It is thought that one of the reasons that TSHR genetic variants are a risk factor for Graves’ is because the changes in the TSHR gene could cause a slightly different structure for the receptor protein and possibly “exacerbate autoimmune respose against TSHR in” Graves’ disease. [ref]
Check your 23andMe results for rs1991517 (v.4 only):
- CC: normal
- CG: slightly lower TSH
- GG: slightly lower TSH [ref]
Check your 23andMe results for rs179247 (v4 only):
- AA: increased risk of Grave’s [ref]
- AG: increased risk of Grave’s
- GG: normal risk of Grave’s
Check your 23andMe results for rs12101255 (v4 only):
- CC: increased risk of Grave’s [ref]
- CT: increased risk of Grave’s
- TT: normal risk of Grave’s
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. Do a search in PubMed if you need further information.
Check your 23andMe results for rs4704397 (v.4, v.5):
- 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
Check your 23andMe results for rs6885099 (v.4, v.5)
- AA: increased serum TSH [ref]
- AG: increased serum TSH
- GG: normal serum TSH
The FOXE1 gene (thyroid specific forkhead transcription factor) has also been identified to increase the risk of primary hypothyroidism[ref] and with changes in TSH levels.
Check your 23andMe results for rs7850258 (v.4, v.5):
- 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 (v.4, v.5):
- AA: decreased TSH, increased risk of thyroid cancer[ref]
- AG: decreased TSH
- GG: normal
AutoImmune Thyroid Gene Variants – 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 (v.4):
- TT: higher frequency of Hashimoto’s (OR 1.4)
- CT: higher frequency of Hashimoto’s
- CC: normal
Check your 23andMe results for rs12101255 (v.4):
- 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 (v.4):
- 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 (v.4, v.5):
- 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 (v.4, v.5):
- TT: higher rT3, lower free T3 [ref]
- CT: lower T3
- CC: normal
Check your 23andMe results for rs225014 (v.4):
- 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… A recent study showed that patients with the rs225014 CC or CT genotype preferred a combo of T3 and T4. (Here is the full text of the study to share with your doctor.)
A recent study suggests that the rs225014 variant affects the bioavailability of T4 treatment and that those with the TT geneotype may need a lower dose than those with the CC or CT genotype. (Here is the full text of the study to share with your doctor)
Rare causes of thyroid disease:
Thyroid Hormone Receptors (THRB, THRA)
The thyroid hormone receptor genes code for the receptor that brings the thyroid hormone into the target cells. Mutations in these genes cause thyroid hormone resistance. Generally, THRB or THRA mutations will cause hypothyroidism that is recognized and diagnosed in infants or children. In other words, the mutations may cause more severe symptoms that affect growth and development.[ref]
Check your 23andMe results for rs28933408 (v.4):
- TT: thyroid hormone resistance [ref]
- GG: normal
Check your 23andMe results for i5003323 (v.4):
- GG: thyroid hormone resistance [ref]
- AA: normal
Check your 23andMe results for i5003327 (v.4):
- TT: thyroid hormone resistance [ref]
- CC: normal
*Note that for anything that is rare or considered pathogenic, you should heed the warnings from 23andMe not to use their data for medical purposes. Their test information could be wrong, and for anything medically important you should probably get a second test from a clinical testing company.
If you are on thyroid medication or under the care of a doctor, please be sure to talk with your doctor about making any changes, including dietary changes, that could affect your thyroid hormone levels.
- Selenium is essential to the conversion of T4 to T3. Brazil nuts are a good source of selenium, and supplements are also available.
- Eat your fruits and veggies: The dietary flavonoid kaempferol, found in apples, onions, leeks, grapes, and other fruits and vegetables, induces DIO2 increasing conversion to T3. [study]
- Glandulars: There are thyroid glandular supplements (dried thyroid gland) which may — or may not! — increase thyroid hormones. The reviews are mixed. 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. The flip side of that is also worth noting — 95% of people with autoimmune thyroid disease may have no problem with gluten.
- Avoid fasting: In studies, fasting and critical illnesses increase the levels of DIO3, which is the enzyme that deactivates thyroid hormone.[study] Fasting (and illness!) may be hard on your supply of active thyroid hormone.
- Blocking blue light: Light and circadian rhythms play a role in DIO3 expression as well.[study] Blocking blue light in the evening (from LED bulbs, TV screens, etc) by wearing blue-blocking glasses will help to keep your circadian rhythm on track.
- Blame mom: Several recent studies have also pointed to the hereditary epigenetic effects on DIO3 as well. [study]
- Myo-insitol? For autoimmune thyroid problems, myo-inositol and selenium have been shown to reduce antibody levels. [study] (Again – the ‘talk to your doctor’ warning here…)
- Vitamin D supplement has been shown to reduce Hashimoto’s antibody levels. [study] This is the vitamin D 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 in your supplement.)
Recent studies on thyroid levels and chemical toxins:
With so many people having problems with thyroid hormone levels, the question becomes: Why now? What is causing this explosion? The foods that we are eating and the fact that we no longer eat the thyroid glands of animals probably plays a role in the hypothyroid epidemic. Additionally, chemicals that are found in nearly everyone’s bloodstream, such as PFOA’s, BPA and phthalates, have been shown in several recent studies to be related to lower thyroid levels. 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] Read more about how genes play a role in your ability to detox BPA and phthalates.
- 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 (a rat study) [study]
More to read:
I encourage everyone who has thyroid problems to read and research more on this issue. YOU are your own best advocate! There is a lot more to learn about the topic:
- Stop the Thyroid Madness II by Janie Bowthorpe (book)
- Hashimoto’s Protocol by Isabella Wentz (book)
- Detailed overview (2008): Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling
Related Genetic Lifehacks Articles:
updated and revised 9/10/18