Thyroxine, also known as T4, is the primary thyroid hormone secreted by the thyroid gland. This hormone is low or depressed in those people with hypothyroidism, and it is usually elevated in those with hyperthyroidism. Although the focus of this post will be on T4, triiodothyronine (T3) is another thyroid hormone. And because most T3 is produced via the conversion of T4 into T3, if someone has low T4 levels then they usually will have low T3 levels, although there are exceptions.
Before talking about some of the factors which can cause low T4 levels, I’d like to briefly discuss how thyroid hormone is manufactured. Because if you understand how it is formed then you will also understand some of the things which can lead to lower thyroid hormone levels. The thyroid follicles are cells in the thyroid gland, and this is where thyroid hormones are produced. You get iodide from the diet, which travels through the bloodstream to the thyroid follicular cells, which in turn takes up the iodide with the help of something called a sodium-iodide-symporter. Thyroid peroxidase is an enzyme which plays an important role in iodination, which involves the oxidation of iodide ions to form iodine atoms.
Thyroxine contains four iodine atoms, which is why it’s referred to as “T4”, and these iodine atoms attach to a tyrosine molecule. And as you might have guessed, triiodothyronine contains three iodine atoms, which is why it’s referred to as “T3”. There is also thyroglobulin, which is synthesized by the thyroid follicular cells, and this acts as a substrate for the synthesis of T3 and T4, and also stores inactive forms of thyroid hormone. So what’s important to understand is that iodine and tyrosine are important for the formation of thyroid hormone, and thyroid peroxidase and thyroglobulin also play important roles.
Hopefully you have a better understanding of how thyroid hormone is formed. Now I’d like to go ahead and look at seven reasons why you might have low T4 levels:
1. Hashimoto’s Thyroiditis. This is an autoimmune condition which involves the immune system attacking the thyroid gland. The immune system specifically attacks thyroglobulin and/or thyroid peroxidase, which in turn is what results in low or depressed thyroid hormone levels. Although many people with Hashimoto’s don’t have low T4 levels, since most medical doctors don’t do anything to address the autoimmune component, the immune system will continue damaging these structures of the thyroid gland, and as a result, over a prolonged period of time most patients with Hashimoto’s will eventually have low T4 levels.
What’s The Solution To This Problem? The goal is to address the autoimmune response. The most important factor is to try to detect and then remove the autoimmune trigger. While doing this you should do things to reduce inflammation and increase regulatory T cells, which I discussed in a separate blog post entitled “Regulatory T Cells and Thyroid Autoimmunity “.
2. Iodine Deficiency. Since iodine is necessary for the formation of thyroid hormone, it should come as no surprise that an iodine deficiency can result in low T4 levels. But how can you determine if you have an iodine deficiency? The most accurate way of testing for iodine seems to be in the urine.
What’s The Solution To This Problem? If someone has an iodine deficiency then the obvious goal should be to correct it. However, not everyone does well when taking iodine, especially many people with Hashimoto’s Thyroiditis, and so if you test positive for an iodine deficiency and are thinking about supplementing with iodine, you do need to be cautious. This is especially true if you are thinking about taking high doses of iodine, but it can also be a problem in some people even in small doses. For those people with Hashimoto’s, many times it is best to restore the health of the immune system before taking iodine.
3. Dysregulation of the HPT Axis. When talking about the formation of thyroid hormone earlier, I didn’t talk about the role of the hypothalamus and pituitary gland. These both play an important role in the signaling of thyroid hormone. Most people are familiar with thyroid stimulating hormone, which is also known as TSH. TSH is released by the pituitary gland, which tells the thyroid gland to produce more thyroid hormone. However, the hypothalamus communicates with the pituitary gland, and so if there are problems with either the hypothalamus or pituitary gland then this in turn can cause problems with the thyroid gland.
What’s The Solution To This Problem? If someone has dysregulation of the hypothalamic-pituitary-thyroid (HPT) axis, then the goal should be to improve the health of the HPT axis. Adaptogenic herbs can help to accomplish this, with ashwagandha perhaps the most well known herb which can have a positive effect on the HPT axis. Taking glandulars to support the hypothalamus and pituitary gland can also help in some cases. However, while taking adaptogenic herbs can help, stress causes dysregulation of the HPT axis, as well as the hypothalamic-pituitary-adrenal (HPA) axis, and so improving your stress handling skills is essential.
4. Tyrosine Deficiency. You learned earlier that tyrosine plays an important role in thyroid hormone production, as the iodine atoms attach to a tyrosine molecule. And while most cases of low T4 levels aren’t caused by a tyrosine deficiency, it’s still something to consider. I spoke about this in greater detail in an article I wrote entitled “Tyrosine and Thyroid Health “.
What ‘s The Solution To This Problem? If someone does have a tyrosine deficiency then they will want to increase their consumption of tyrosine-rich foods such as chicken, turkey, fish, eggs, avocados, and spinach. Taking a tyrosine supplement might also be a good idea if one has a deficiency..
5. Iron deficiency. As you have learned, the enzyme thyroid peroxidase plays an important role in thyroid hormone formation. Thyroid peroxidase is a heme-containing enzyme, which means that it is dependent on iron. And the research shows that an iron deficiency can reduce thyroid peroxidase activity, which in turn can affect thyroid metabolism (1)  (2) .
What’s The Solution To This Problem? Many people are deficient in iron, and so before ruling out an iron deficiency you want to make sure to get a complete iron panel consisting of serum iron, ferritin, iron saturation, and TIBC. If you have an iron deficiency then supplementation probably is a good idea. However, you also want to try addressing the cause of the problem, which I spoke about in an article entitled “Iron Deficiency Anemia and Thyroid Health “.
6. Environmental toxins. Certain environmental toxins can potentially inhibit thyroid activity. Numerous studies show that xenoestrogens such as BPA and flame retardants can inhibit thyroid hormone production (3)  (4)  (5) . Other studies also show that fluoride can interfere with thyroid gland function (6)  (7) . Bromide might also have an inhibitory effect on thyroid hormone (8) . Perchlorate inhibits the uptake of iodine and can decrease thyroid hormone production (9) . Heavy metals such as mercury can also inhibit thyroid hormone production (10)  (11) .
What’s The Solution To This Problem? Although it’s impossible to eliminate your exposure to environmental toxins, you of course can do things to minimize your exposure to them. For example, you want to avoid drinking bottled water on a frequent basis, reduce your exposure to flame retardants, along with fluoride, and other environmental toxins.
7. Soy and other goitrogenic foods. This one is controversial, as while there are studies which show that soy phytoestrogens can cause hypothyroidism (12) , other studies show that this isn’t the case (13) . Other studies suggest that soy only has antithyroid effects in the presence of an iodine deficiency (14) . With regards to other goitrogenic foods (i.e. cruciferous vegetables, spinach, strawberries, etc.), there are no human studies I’m aware of which show that eating these foods inhibit thyroid activity.
What’s The Solution To This Problem? Besides the possibility that soy has goitrogenic properties, soy is a common allergen, and most soy is also genetic modified. And so it might be best to minimize your consumption of soy. With that being said, some people are able to eat some organic fermented soy without a problem, although not everyone. As for other goitrogenic foods, such as cruciferous vegetables, most people are able to eat these without a problem, although if someone has a moderate to severe iodine deficiency then it might be best to play it safe and limit your consumption of these foods. However, keep in mind that cooking these foods will also reduce the goitrogenic activity.
In summary, there are numerous factors which can cause low T4 levels. Hashimoto’s Thyroiditis is the primary cause of hypothyroidism. Nutrient deficiencies can also play a role, including iodine, iron and tyrosine. Other potential causes include dysregulation of the HPT axis, certain environmental toxins, and perhaps certain goitrogenic foods.