Most people reading this understand the importance of the thyroid gland, as it produces the thyroid hormones, which of course I’ll be discussing in this blog post. The truth is that all of these markers I’ll be discussing either directly or indirectly affect the thyroid hormones, which play an important role in regulating metabolism, gene expression, brain development, reproductive health, bone health, and wound healing.
For most of the markers I’ll list the lab reference ranges according to Labcorp and Quest Diagnostics, which are two of the most well known labs in the United States. Just keep in mind that different labs will have different reference ranges, which is why you usually want to pay attention to the optimal reference ranges I have listed below. For some markers I haven’t listed optimal reference ranges, simply because I don’t know what the optimal reference range is for every single marker.
It’s also important to mention that some markers will have different ranges for males and females, as well as different ranges based on the age of the patient. For example, according to Quest Diagnostics, the lab reference range for free T4 for those 2 to 12 years in age is 0.9-1.4 ng/dL, but those people over 20 years old should have a reference range between 0.8-1.8 ng/dL. For simplicity sake I only listed the reference ranges for adult females.
THYROID STIMULATING HORMONE (TSH)
The production of thyroid hormones is regulated by thyroid stimulating hormone (TSH), which is made by the anterior pituitary gland. TSH also influences the size of the thyroid gland. While TSH stimulates the production of thyroid hormones, these same thyroid hormones will inhibit the production of TSH. So it’s a negative feedback mechanism, as if the thyroid hormone levels get too high then the TSH will stop signaling the thyroid gland to produce thyroid hormone, and if the thyroid hormone levels get too low the TSH will increase in an effort to tell the thyroid gland to produce more thyroid hormone.
TSH during hypothyroidism. High TSH levels typically are associated with an underactive thyroid gland. In other words, if someone has depressed or less than optimal thyroid hormone levels then the TSH will typically increase. As mentioned above, what happens is that when the thyroid hormone levels become too low the pituitary gland will produce more TSH in order to stimulate the thyroid gland to produce more thyroid hormones. Sometimes the TSH will be quite elevated, where it is obvious to any doctor that the person has a thyroid problem (or possibly a pituitary issue). But what happens more frequently is that the TSH is within the lab reference range, but outside of the “optimal” reference range. Unfortunately many medical doctors don’t look at the “optimal” reference range, but will only pay attention to a marker if it is out of range.
TSH during hyperthyroidism. On the other hand, someone with an overactive thyroid (hyperthyroidism) will usually have a low or depressed TSH. The reason for this is because when someone has elevated thyroid hormone levels this will cause the pituitary gland to produce less TSH so that the thyroid gland will stop or slow down thyroid hormone production. It’s important to understand that in most cases of hyperthyroidism where someone is taking antithyroid medication (i.e. methimazole) or antithyroid herbs (i.e. bugleweed) the thyroid hormone levels will start decreasing before the TSH starts increasing. In fact, it’s very common to see someone take antithyroid medication or bugleweed who has normal thyroid hormone levels, but their TSH is still depressed. In most cases the TSH will eventually increase and normalize.
Labcorp: 0.450-4.50 uIU/ml
Quest: 0.40-4.50 uIU/ml
Optimal reference range: 1.0 to 2.0 uIU/ml
TOTAL THYROXINE (TOTAL T4)
Thyroxine, also known as T4, is a type of thyroid hormone. Approximately 85% of thyroid hormone released by the thyroid gland is T4, with approximately 15% being T3. When looking at total T4, you need to keep in mind that most of the T4 is protein-bound. In other words, most of the T4 produced by the thyroid gland (as well as T3) binds to a protein, which is then transported around the bloodstream. I’ll discuss this in greater detail when I talk about thyroid-binding globulin below.
Total T4 during hypothyroidism. Hypothyroidism is characterized by low thyroid hormone levels, including total T4. It’s important to mention that many people with Hashimoto’s thyroiditis have subclinical hypothyroidism, which is characterized by an elevated TSH and normal thyroid hormone levels. Many times in those with Hashimoto’s the total T4 will be within the lab reference range, but below the optimal reference range.
Total T4 during hyperthyroidism. Those with overt hyperthyroidism will usually have elevated total T4 levels, although there are times when I see the free T4 elevated and the total T4 on the high side, but within the lab reference range.
Labcorp: 4.5−12.0 mcg/dL
Quest: 5.1-11.9 mcg/dL
Optimal reference range: 6.0 to 11.0 pg/ml
FREE THYROXINE (FREE T4)
Free T4 represents the free form of thyroxine in the blood. When discussing total T4 I mentioned that most of the T4 is bound to a protein, with a very small percentage being free. So just to clarify the difference between total T4 and free T4, the total T4 looks at the BOTH the T4 that’s bound to a protein and the free T4 in circulation, whereas when testing the free T4 by itself this obviously is only looking at the free form of the hormone.
Free T4 during hypothyroidism. Hypothyroidism is characterized by low thyroid hormone levels, including free T4. As is the case with the total T4, if someone has subclinical hypothyroidism then they will have an elevated TSH and free T4 levels that fall within the lab reference range, although they might be less than the optimal reference range.
Free T4 during hyperthyroidism. Those with overt hyperthyroidism will have elevated free T4 levels. If someone has subclinical hyperthyroidism they will have a depressed TSH and free T4 levels that fall within the lab reference range, although sometimes they will be on the high end of the range. If someone with hyperthyroidism is receiving treatment with antithyroid medication (or antithyroid herbs), free T4 is the test of choice to determine whether the treatment is working since the TSH may remain low for weeks to months. So as I mentioned earlier, for those with a depressed TSH and elevated thyroid hormone levels who are taking antithyroid medication, it’s common to see the TSH remain depressed for quite awhile, even when the thyroid hormone levels are decreasing in response to the antithyroid medication.
Labcorp: 0.82-1.77 ng/dL
Quest: 0.8-1.8 ng/dL
Optimal reference range: 1.1 to 1.5 ng/dL
TOTAL TRIIODOTHYRONINE (TOTAL T3)
Total T3 consists of both the bound form of T3 and the free T3 in circulation. So just as is the case with total T4, with total T3 you’ll have most of the T3 bound to a protein, and a small percentage of the hormone is free, and can therefore bind to the thyroid hormone receptors. When you think about it this makes sense, as you wouldn’t want all of your thyroid hormones to bind to thyroid receptors simultaneously, and so most of them are attached to proteins, and when needed they are released and become the free form, which will bind to the thyroid hormone receptors and have physiological effects.
Total T3 during hypothyroidism. If someone has overt hypothyroidism then they will see total T3 levels below the reference range, but in subclinical hypothyroidism the total T3 will be within the lab reference range, although it might be below the optimal reference range listed below.
Total T3 during hyperthyroidism. Those with overt hyperthyroidism will usually have elevated total T3 levels.
Labcorp: 71−180 ng/dL
Quest: 76-181 ng/dL
Optimal reference range: 100-160 ng/dL
FREE TRIIODOTHYRONINE (FREE T3)
Triiodothyronine is the active form of thyroid hormone, and the free form of the hormone (free T3) is what binds to the thyroid hormone receptors.
Free T3 during hypothyroidism. If someone has overt hypothyroidism then they will have a free T3 below the lab reference range. If someone has subclinical hypothyroidism then they will have an elevated TSH and free T3 levels that fall within the lab reference range, although they might be less than the optimal reference range. It’s also important to know that many people have problems converting T4 to T3, which will show up on a lab as a normal free T4 with a low or depressed free T3, and I’ll discuss some of the common causes of conversion problems when discussing reverse T3.
Free T3 during hyperthyroidism. Those with overt hyperthyroidism will have elevated free T3 levels. If someone has subclinical hyperthyroidism they will have a depressed TSH and free T3 levels that fall within the lab reference range, although sometimes they will be on the high end of the range. It’s also worth mentioning that some patients with hyperthyroidism have “T3 toxicosis” where the T4 is normal but there is an elevation of T3 (1).
Labcorp: 2.0-4.4 pg/ml
Quest: 2.3-4.2 pg/ml
Optimal reference range: 3.0 to 3.7 pg/ml
The number “4” in T4 means that it has 4 iodine molecules, and if it loses one of them it will yield either T3 or reverse T3, depending on which iodine molecule it loses. So reverse T3 is manufactured from T4, and the role of reverse T3 is to block the action of T3. When testing the reverse T3 the main concern is having elevated levels.
Reverse T3 during hypothyroidism. One of the most common problems I see with patients is a problem converting T4 to T3. There can be numerous causes of this, but regardless of the cause, when this occurs it’s common to see an elevated reverse T3. Since most of the conversion of T4 to T3 takes place in the liver, having a liver problem can affect the conversion of T4 to T3, and thus cause an elevated reverse T3. Some of this conversion also takes place in the gut, and thus an unhealthy gut microbiome can be a factor in an elevated reverse T3. Elevated cortisol levels can also affect the conversion of T4 to T3, and even inflammation can be a factor. Anything that results in a decrease of T4 to T3 conversion can cause an elevated reverse T3.
Reverse T3 during hyperthyroidism. Most people with hyperthyroidism and Graves’ disease will have an elevated reverse T3. The reason is because with hyperthyroidism there is an excessive amount of T4, and while a lot of this will convert to T3, a good amount of reverse T3 will also be manufactured from the high levels of T4.
Labcorp: 9.2-24.1 ng/dL
Quest: 8-25 ng/dL
Optimal reference range: 10-18 ng/dL
FREE THYROXINE INDEX (FTI)
Most doctors order the free T4 instead of the free thyroxine index (FTI), although every now and then I’ll still see this on a report. The FTI is determined by the following calculation: Thyroxine (T4)/Thyroid Binding Capacity.
Hyperthyroidism usually causes increased FTI and hypothyroidism causes decreased values. The FTI isn’t something I specifically recommend for my patients to order, although some thyroid panels will include this marker.
Labcorp: 1.2-4.9 mg/dL
Quest: 1.4-3.8 mg/dL
Optimal reference range: 1.5-3.7 mg/dL
The T3 uptake measures the amount of receptor sites available on thyroxine-binding globulin (TBG). So essentially it is an indirect measurement of TBG binding capacity. The more binding sites that are available on TBG, the lower the T3 uptake will be. So for example, if someone has hyperthyroidism and has a high total T4, they will have less available binding sites since there is an excessive amount of thyroid hormone bound to those proteins, and this will usually result in a high T3 uptake. On the other hand, if someone has low total T4 levels, they will have more binding sites available on TBG, and this will have a lower T3 uptake.
Optimal reference range: 25-33%
THYROXINE-BINDING GLOBULIN (TBG)
Thyroxine-binding globulin (TBG) is manufactured by the liver, and is one of the proteins responsible for transporting thyroid hormones from blood to tissues. So both T4 and T3 bind to TBG and are transported to the target tissues. As a result, an increase or decrease of TBG can alter the total concentrations of T4 and T3 in the blood. For example, estrogen therapy (or taking oral contraceptives) can increase TBG, which means that TBG will bind to more thyroid hormones, which will decrease the free hormone available in the blood. So in this case we commonly would see a high total T4 and a low free T4.
On the other hand, corticosteroids will lower TBG levels, and so TBG will bind to less thyroid hormone levels. This will result in low total and free thyroid hormones. I know this might be a little confusing to some reading this, but the truth is that TBG is a marker that most people don’t need to test for.
Labcorp: 13−39 mcg/mL
Quest: males (12.7-25.1 mcg/mL); females (13.5-30.9 mcg/mL)
Optimal reference range: 18-27 mcg/mL
THYROID PEROXIDASE (TPO) ANTIBODIES
Thyroid peroxidase (TPO) is an enzyme involved in the synthesis of T3 and T4, as it converts iodide to iodine, and the iodine combines with tyrosine on thyroglobulin. This in turn forms T4 and T3. Anti-TPO antibodies are the most common type of thyroid autoantibody, as it is present in most people with Hashimoto’s thyroiditis, and many people with Graves’ disease also have elevated anti-TPO antibodies. Since TPO is involved in the synthesis of T3 and T4, having elevated anti-TPO antibodies can lead to the decreased enzymatic production of thyroid hormone. Anti-TPO antibodies are also frequently seen in the general population and are 5-fold more common in women than in men.
Labcorp: 0-34 IU/ml
Quest: <9 IU/ml
Optimal reference range: <9 IU/ml
Thyroglobulin is a glycoprotein that is produced by thyroid follicular cells. T4 and T3 are synthesized on thyroglobulin within the lumen of thyroid follicles. Conventional medical doctors use thyroglobulin as a tumor marker, although research shows that elevated levels can also indicate an iodine deficiency (2) (3). Because thyroglobulin is only produced by thyroid follicular cells, if someone has a total thyroidectomy they should have an undetectable thyroglobulin level, and the same is true for many people who receive radioactive iodine treatment.
Labcorp: 1.4-29.2 ng/mL
Quest: unable to find reference range
Other Lab: 1.7-56.0 ng/mL
Optimal reference range: 2.0-29.2 ng/mL
I just discussed what thyroglobulin is, and so when someone has elevated anti-thyroglobulin antibodies, this means that the immune system is damaging thyroglobulin, which over time can lead to hypothyroidism. These anti-thyroglobulin antibodies are associated with Hashimoto’s thyroiditis. When looking at the lab reference ranges from Labcorp and Quest Diagnostics you’ll see that both ranges suggest that there should be almost no anti-thyroglobulin antibodies, whereas some labs will have much higher ranges, even though they are using the same units.
Labcorp: 0.0-0.9 IU/ml
Quest: <1 or = 1 IU/ml
Other Lab: <20 IU/ml
Optimal reference range: <1 IU/ml
TSH RECEPTOR ANTIBODIES (TRAB)
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. These antibodies bind to the TSH receptor, which causes thyroid growth, increases the vascularity of the thyroid gland, and causes an excessive production of thyroid hormone.
There are also blocking TRABs, also known as thyrotropin-binding inhibiting immunoglobulins, which can be found in approximately 15% of patients with thyroid autoimmunity (4).
Regarding the reference ranges, I’m going to specifically list the ranges for the thyroid stimulating immunoglobulins below, since this is the most common antibody associated with Graves’ disease. However, it’s important to know that recently some of the labs (including Labcorp) changed the units associated with this marker. As a result, when retesting this marker it would be a good idea to use the same lab for comparison purposes.
Labcorp: 0.00-0.55 IU/L
Quest: <140% Baseline
Optimal reference range: <0.55 IU/L or <80%
Calcitonin is usually measured if someone is suspected to have medullary thyroid cancer, which is a rare form of thyroid cancer that usually causes an increase in calcitonin. As a result, it’s not something I commonly test for in my practice.
Labcorp: Male: 0.0−8.4 pg/mL; female: 0.0−5.0 pg/mL
Quest: unable to find reference range
Two Other Thyroid-Specific Diagnostic Tests Worth Mentioning:
An ultrasound uses sound waves to develop images, and many endocrinologists will recommend a thyroid ultrasound to their patients with Graves’ disease and Hashimoto’s. There are a few benefits of thyroid ultrasounds, as they are non-invasive, they don’t use ionizing radiation, and they’re not as costly as other imaging techniques (i.e. CT scan, MRI). But does this mean that everyone with a thyroid or autoimmune thyroid condition should receive a thyroid ultrasound?
I discussed this in detail in a past blog post I wrote entitled “Should You Get a Thyroid Ultrasound?” In the post I discussed the indications of a thyroid ultrasound according to the American Association of Clinical Endocrinologists. If you haven’t had a thyroid ultrasound done and are wondering if you need one I would recommend to check out this blog post.
RADIOACTIVE IODINE UPTAKE TEST
This test involves either swallowing or injecting a small amount of radioactive iodine, which allows practitioners to see how active the thyroid tissue is. The way this test works is that the thyroid gland absorbs the small dosage of radioactive iodine, and is evaluated after six hours and 24 hours. Graves’ disease is typically characterized by a high uptake of radioactive iodine.
While many endocrinologists will recommend the radioactive iodine uptake test to confirm or rule out Graves’ disease, most of the time this test is unnecessary. In fact, if someone has hyperthyroidism in the presence of elevated TSH receptor antibodies then this confirms Graves’ disease. While some doctors will recommend the radioactive iodine uptake test to see if someone has “hot” or “cold” nodules, you can’t confirm or rule out a malignant thyroid nodule with the radioactive iodine uptake test alone.
Which Of These Markers Have You Tested For?
I’d love to hear which of these markers you have tested for. I assume most reading this have had some of the basic thyroid markers (TSH, free T3, free T4), and many have also had the thyroid antibodies tested. If there are any other blood test markers and/or other thyroid-specific tests you think I should have included in this blog post please let me know!