Understanding Thyroid Blood Chemistry

Most people with thyroid and autoimmune thyroid conditions don’t have a good understanding when it comes to the different types of serum tests used to evaluate thyroid health. Although it is true that blood tests don’t tell the entire story, I do think it’s important for people who choose to follow a natural treatment protocol to at least have a basic knowledge of the different types of blood tests. As a result, I’ve decided to put together a post which discusses the most important “thyroid” blood tests.

Thyroid stimulating hormone (TSH). Although many medical doctors primarily pay attention to the TSH, it’s important to understand that the TSH is actually a pituitary hormone. The role of the TSH is to stimulate the thyroid gland to produce the thyroid hormones (T3 and T4). It is synthesized and released by the anterior pituitary gland. So when someone has a hypothyroid condition, which is characterized by low or depressed thyroid hormone levels, the pituitary gland will secrete more TSH. This explains why the TSH is high in hypothyroid conditions. Due to the decrease in thyroid hormone, greater amounts of TSH will be released. On the other hand, if someone has a hyperthyroid condition, this of course is characterized by an excess of thyroid hormone. As a result, the pituitary gland will stop secreting TSH because it doesn’t want to stimulate the thyroid gland to produce more thyroid hormone. Because of this the TSH will be depressed.

Why do most medical doctors focus on the TSH when someone with hypothyroidism or Hashimoto’s Thyroiditis is taking synthetic thyroid hormone (i.e. levothyroxine)? The reason is because taking synthetic thyroid hormone will usually help to lower the TSH, but it won’t have an effect on the actual thyroid hormone levels. So when someone has Hashimoto’s Thyroiditis and is given synthetic thyroid hormone, most medical doctors will ignore the autoimmune response, as their primarily goal is to get the TSH within the normal reference range.

There of course are a few problems with this. The first problem is that taking thyroid hormone isn’t doing anything to address the autoimmune response. Another issue is that the upper end of the lab reference ranges tend to be too high with regards to TSH. For example, a common lab reference range is between .8 and 4.5 mlU/L. However, the functional reference range is between 1.0 and 3.0, and some claim that it should be between 1.0 and 2.0. But even if you get someone’s TSH between the functional reference range, many people still don’t feel well because the underlying cause of their condition hasn’t been addressed.

Free T3 and Total T3. Triiodothyronine, also known as T3, is a type of thyroid hormone. This is the active form of thyroid hormone which is important in regulating the body’s metabolism. The free T3 represents the free form of triiodothyronine in the blood. On the other hand the total T3 represents both the free and bound form of triiodothyronine. Over 90% of T3 is bound to proteins, and while I do think there is value in testing the total T3, because the free T3 is the active form of the hormone then it makes sense to test this as well. Although some T3 is produced directly from the thyroid gland, most of the T3 is produced through the conversion of T4. In hyperthyroid conditions the free T3 and total T3 are usually high, while in hypothyroid conditions the free T3 and total T3 are usually on the low side.

Which of these two values should be tested? Well, ideally it would be great for both of them to be tested. However, if someone has to choose between the two then it really depends on what one is looking for. As an example, if someone wants to monitor the thyroid hormone levels to see if someone has high or low thyroid hormone levels, it is usually preferable to test for the Free T3 since it is the unbound form of the hormone and thus is what produces a biological response. For example, if someone has hyperthyroidism, ultimately it’s the high levels of Free T3 which lead to the hyperthyroid symptoms. On the other hand, if someone wants to determine whether T4 is being properly converted into T3, then either the total T3 or the free T3 will be fine to measure. Or they might want to look at the reverse T3, which I will discuss shortly.

T3 Uptake. Thyroid-binding globulin (TBG) is what binds thyroid hormone, and helps to carry both T3 and T4 in the bloodstream. The T3 uptake test tells us how much TBG is bound by T4. For example, when TBG concentration is decreased, less TBG is available to bind labeled triiodothyronine (T3), and more labeled T3 reagent binds to the solid-phase material (increased T3 uptake) (1). T3 uptake is typically increased with hyperthyroid conditions, and decreased with hypothyroid conditions. Keep in mind that other factors can cause an increase in T3 uptake (i.e. anabolic steroids such as testosterone), while some other factors can cause a decrease in T3 uptake, such as xenoestrogens.

Free T4 and Total T4. Thyroxine, also known as T4, is a type of thyroid hormone. Just as is the case with T3, the free T4 represents the free form of thyroxine in the blood, whereas the total T4 represents both the free and bound form of thyroxine. As I mentioned before, T4 is converted into T3. In hyperthyroid conditions the free T4 and total T4 are elevated, while in hypothyroid conditions the free T4 and total T4 are on the low side.

It’s also important to understand that synthetic thyroid hormone consists of T4. Even though it is synthetic, the body can still convert it to triiodothyronine (T3). However, some people have problems with the conversion process and are given synthetic T3 (i.e. Cytomel). Natural thyroid hormone consists of both T4 and T3, as well as T1 and T2, which I won’t be discussing in this blog post.

Which of these two values should be tested? Free T4 or total T4? As I mentioned with triiodothyronine, it would be wonderful if both the total T4 and free T4 can be tested. But if choosing only one of these tests then one wants to look at the free form of the hormone. Fortunately most endocrinologists realize this and will test for free T4. However, there are some who will only test for total T4 and not free T4.

Thyroid-Binding Globulin (TBG). I briefly mentioned this test earlier, as this is a protein that moves the thyroid hormones throughout your body. One will typically see increased TBG levels in hypothyroidism, and decreased TBG levels in hyperthyroidism. However, other factors can cause this to increase or decrease. For example, certain drugs can increase TBG levels such as oral contraceptives. Liver disease can also increase these levels, and TBG levels are normally increased during pregnancy. On the other hand, certain drugs such as prednisone, dilantin, and high doses of salicylates can decrease TBG levels.

Free Thyroxine Index (FTI). The free thyroxine index was used more commonly before the free T3 and free T4 tests were made available. It is obtained by multiplying the total T4 with the T3 uptake, and might be useful to measure thyroid function when there are abnormalities in plasma protein binding. The free thyroxine index is typically high in hyperthyroidism, and usually low in hypothyroidism.

Reverse T3 (RT3). As I mentioned earlier, T4 is converted to T3. However, some T4 is also converted to reverse T3. I won’t get into much detail about reverse T3 here, as for more information you can read a separate article I wrote entitled “Reverse T3: What You Need To Know About It“. What I will say here is that some reverse T3 is normal, but you don’t want to have too much, as this usually indicates a conversion problem between T4 and T3. And as I mentioned in the article, chronic stress frequently leads to high RT3 levels. The reason for this is because elevated cortisol levels can inhibit the conversion of T4 to T3. Since the liver is also responsible for the conversion of T4 to T3, having a liver that isn’t functioning optimally can also lead to higher levels of RT3.

Thyroid peroxidase (TPO) antibodies. Thyroid peroxidase, also known as thyroperoxidase, is an enzyme produced by the thyroid gland which helps with the production of thyroid hormone. In fact, when someone takes antithyroid medication (i.e. methimazole or PTU), this essentially is inhibiting this enzyme. Thyroid peroxidase antibodies inhibit thyroid peroxidase, and so the thyroid gland is unable to produce sufficient amounts of thyroid hormone. This typically results in elevated TSH levels. And while taking synthetic or natural thyroid hormone can help to lower the TSH, it won’t do anything to address the autoimmune response, and thus lower these antibodies. TPO antibodies are frequently high in Hashimoto’s Thyroiditis, although it’s not uncommon for those with Graves’ Disease to have elevated levels of these antibodies as well.

Thyroglobulin antibodies. Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thyroid gland (2). It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine (2). In other words, thyroglobulin is a protein produced by the thyroid gland, and it is important for the synthesis of T3 and T4. Thyroglobulin antibodies attack and damage this protein, which leads to the decreased production of thyroid hormone. Elevated thyroglobulin antibodies are common in people with Hashimoto’s Thyroiditis, although some people with Graves’ Disease can have these antibodies as well.

TSH receptor antibodies (TRAbs). There are two types of TSH receptor antibodies. Thyroid stimulating antibodies (TSAb), also known as thyroid stimulating immunoglobulins (TSI), are the main antibodies associated with Graves’ Disease. They stimulate or bind to the TSH receptors, which in turn cause the thyroid gland to produce excessive amounts of thyroid hormone. These antibodies can also attack the tissues of the eye, and can therefore cause thyroid eye disease, also known as Graves’ opthalmopathy. There are also TSH-stimulation blocking antibodies( TSBAb), which causes hypothyroidism. TSBAb-positive patients with hypothyroidism and Graves’ patients with hyperthyroidism may have both TSBAb and TSAb (3).

One important thing to keep in mind is that the absence of thyroid antibodies doesn’t necessarily rule out autoimmune thyroid disease. While testing positive for these antibodies will confirm the presence of an autoimmune thyroid condition, these antibodies can fluctuate, which is why you never want to rely on a single reading. As a result, if an autoimmune thyroid condition is suspected, yet the person tests negative for thyroid autoantibodies, it would be a good idea to test these again in a few months.

So hopefully you have a better understanding of the different types of thyroid blood tests available. While some medical doctors only test for the TSH and thyroid hormone levels, the other tests do have some value. However, also keep in mind that while these tests can provide valuable information, one can’t rely on blood tests alone. For example, just because someone has their TSH and thyroid hormone levels within the normal reference range doesn’t mean they don’t have a problem with the thyroid gland. Remember that the thyroid antibodies will develop before the TSH and thyroid hormone levels become out of range. In fact, with a condition such as Hashimoto’s Thyroiditis, the thyroid antibodies might be elevated for many years before they cause significant damage to raise the TSH and eventually decrease the thyroid hormone levels.