This introductory article is one of many in-depth articles on thyroid function. This one will focus on: normal thyroid anatomy and physiology and the tests that are sometimes done to investigate thyroid health.
Basic Physiology and Anatomy
The most important anatomical structures are shown in Figure 1.
The hypothalamus creates a hormone called thyrotropin-releasing hormone (TRH). Although we can measure this in the blood, it is not done routinely. It will be tested in cases where we think the hypothalamus is dysfunctional.
TRH signals the Anterior Pituitary Gland, which then releases Thyroid Stimulating Hormone (TSH). TSH is very commonly measured. In fact, it’s one of the most commonly run blood tests. Click here for an article on the pitfalls of testing Thyroid hormone alone.
TSH then stimulates the thyroid gland, which in turn releases the thyroid hormones (T3 and T4). It is T3 and T4 that actually perform the actions of the thyroid gland (see below). Testing T3 and T4 in the blood is not always necessary, but for some people, these two tell a more complete picture of thyroid health. Click here for an article on Conversion Issues pertaining to Thyroid Hormones for a deeper explanation of when and why we must test these hormones.
Once T3 and T4 leave the thyroid gland, they can then go to any cell throughout the body. Cells will have thyroid hormone receptors – to which T3 and T4 will bind. Once bound, the target cells will undergo changes and carry out the roles of thyroid hormones.
What the Thyroid Gland Does
In reality – it’s a complex network of organs and hormones working together. It’s mainly T3 (and to a lesser extent T4) that ‘act’ on other tissues imparting the action of the thyroid gland. As Figure 1 shows above, there are many steps involved in producing T3 and T4, and each step needs to work for optimal thyroid function.
The thyroid hormones (T3 and T4) are involved in :
- Heart Rate
- Central and peripheral Nervous systems
- Metabolism (Body Weight, temperature)
- Muscle activity
- Menstrual cycles
- cholesterol metabolism
- and much more
Some Important Terms
When you read about thyroid function, some terms are used a lot – I will also refer to these terms in many of my articles.
Euthyroid State: describes NORMALLY functioning thyroid activity.
Hypothyroid State: describes LOW functioning thyroid activity.
Hyperthyroid State: describes HIGH functioning thyroid activity.
Thyroid Function Tests: These are usually blood tests. They measure things like TSH, T3, T4 and another one called reverse T3 (which will be discussed later). When assessing thyroid function, doctors will use Clinical Assessment (signs, symptoms, physical exams) as well as these Laboratory Thyroid Function Tests in making diagnoses and prescribing treatment.
Thyrotopin: another term for Thyroid Stimulating Hormone (TSH). It is made by the pituitary gland, and signals the thyroid gland to make more thyroid hormone (T3 and T4)
Normal T3 and T4 Physiology
T3 and T4 are named the way they are because it describes their composition. T3 is made up of a Tyrosine molecule and 3 iodines. T4 is made up of a Tyrosine molecule and 4 iodines.
In the normal, healthy thyroid (euthyroid state), the thyroid gland secretes about 85–90% T4 and 10–15% T3 .
T4 better for transport; T3 more biologically active
The thyroid gland releases more T4, which is actually a more stable, durable molecule than T3. T4 has to travel through the blood system to get to the tissues. Being tough and durable is useful for the trip from one place to another. However, once it gets to the tissue, T4 needs to convert to T3. T3 is actually more biologically active – meaning it binds stronger to, and produces a stronger effect on the target cells. Click here to read more about this conversion process and how some people have conversion issues which may complicate their blood work.
Bound versus Free Thyroid Hormone
The diagrams above simplified the whole relationship between T3 & T4 and TSH. In reality, when they circulate the blood, T3 and T4 are heavily (>99.5%) protein bound to thyroxine binding globulin (TBG), albumin and transthyretin (prealbumin) . These protein carriers serve one purpose – to take the thyroid hormones safely to the cells that need them.
When bound to protein, thyroid hormones are actually inactive. The remaining 0.5% of thyroid hormone is considered free. Free thyroid hormone is the only one able to act on tissue. That is to say only free hormone is biologically active. When the carrier protein with its bound thyroid hormone gets to the target cells, the thyroid hormone should be released, making it free and therefore biologically active.
Commonly Run Thyroid Function Tests
Thyroid function tests are the blood tests done to assess thyroid function; they are one of the most commonly requested lab investigations (1).
In the majority of cases, the results of thyroid function tests (TFTs) are straightforward, presenting a pattern that is readily recognised and consistent with the clinical impression of thyroid status .
Commonly, TSH will be done for routine screening of thyroid health. Even minor changes in Thyroid hormone (T3 and T4) will change TSH levels significantly . Some doctors and labs will offer T4 (and sometimes T3) for a more comprehensive look, but in most cases, TSH is measured alone.
If Thyroid hormones (T3 & T4) are low a signal is sent to the pituitary to make more TSH. TSH will then signal the thyroid gland to make more T3 and T4.
This is what happens in a hypothyroid state. The patient’s body has low amounts of thyroid hormone circulating causing a rise in TSH.
Likewise, if thyroid hormones (T3 & T4) are high a signal is sent to the pituitary to reduce TSH. This means the thyroid gland will stop making T3 and T4.
This is what happens in a hyperthyroid state. The patient’s body has high amounts of thyroid hormone circulating causing a drop in TSH.
A lot of doctors will rely solely on TSH to assess thyroid function. If TSH is high, the patient has low functioning thyroid; if TSH is low, the patient has a thyroid gland functioning too much. This works most of the time, but there are good reasons to not solely rely on TSH to assess thyroid function. Click here for an article outlining the pitfalls of relying solely on TSH.
T3 and T4 (Free and Total)
As I mentioned above, thyroid hormone (T3 and T4) exist in two forms – total and free. The thyroid hormone levels are included in some cases for a more comprehensive analysis.
Total T4 and total T3 measurements are less accurate because several medications and medical conditions can interfere with the protein carriers that bind to thyroid hormones and confuse results .
Free hormone levels are preferred as they are more indicative of true thyroid function. Measurement of the total levels is still frequently used because many laboratories cannot perform free thyroid measurements .
Reverse T3 (R-T3)
This is another product that can be made from T4. Similarly to how T3 is made through conversion of T4 through enzymatic reactions, reverse T3 can also be made. The difference between T3 and rT3 is that rT3 is not biologically active, yet it can bind where T3 normally does. It is actually a defense mechanism – when there is enough T3 in the system, rT3 will be made to protect the body from over stimulation of thyroid hormone.
Unfortunately, there can be faulty rT3 production too. This is often the case in a situation called Low T3 Syndrome – where there is adequate TSH and T4, but not enough T3 in the system. Various factors can cause pathological amounts of reverse T3 to be created, such as stress, inflammation and certain nutrient deficiencies. This topic is covered here in more depth.
Antibodies are often tested (in the blood) when autoimmune disease is suspected. There are different antibodies that can be tested, and the presence of each one points to a different pathology or disease.
Summary of Normal Findings of Common Tests
|TSH – Thyroid Stimulating Hormone||Free T4 – Thyroxine||Free T3 – Triiodothyroxine||Reverse T3- rT3||Antibodies|
|· Released by the Pituitary gland
· Stimulates the thyroid gland to make Thyroid hormones (T3 & T4)
· If TSH is high, it implies that T3 and T4 must be low (hypothyroidism)
· IF TSH is low, it implies T3 and T4 must be too high (hyperthyroidism)
|· One of two thyroid hormones produced by the thyroid gland
· T4 is made in higher proportions than T3 but T3 is more active. 85-90% of the hormone the thyroid gland produces is T4.
· Once it gets to the target cells, T4 must convert to T3
|· One of two thyroid hormones produced by the thyroid gland
· The other thyroid hormone, T4, will be converted into T3 (enzyme dependant).
· This is the one that is more active, and imparts the functions of the thyroid on the target organs
|· When there’s sufficient T3, the body will convert excess T4 into rT3.
· rT3 will bind to the same receptors of T3 but has no action
· rT3 can be made in normal situations or can be made in excess due to other reasons
|Thyroid Peroxidase Ab
· These target the enzyme (thyroid peroxidase) which converts T4 into active T3
· This targets a protein called Thyroglobulin, which is present in the thyroid gland.
· The auto-immune destruction will cause damage to the thyroid gland itself, resulting in altered thyroid hormone output.
“Naturopathic” Range: Below 2.5 mlU/L
Fertility Range: <2 mlU/L
|Normal Range: 10-23 pmol/L
|Normal Range: 3.5-6.5 pmol/L||Normal Range: 200-300 pmol/L||Normal Ranges
TPO Ab: <35
|Optimal T4/T3 range is about 5:1||Women who test positive for these anti-bodies will generally develop hypothyroidism at a rate of 20% per year. Not everyone with elevated Ab will even show signs of hypothyroidism, It’s important to know for when a woman wants to become pregnant.|
*Naturopathic Ranges: these are values that I often use instead of the lab reported ‘normal values’. It’s important to realize – the definition of reference ranges are based on being ‘disease free’. I believe there is a significant difference between being ‘disease free’ and ‘optimal’: hence the different ranges for TSH and T4.
When Labs Don’t Make Sense
As mentioned above, most cases are straightforward – an ideal situation is when the lab values make sense with the patients’ symptoms matching their results. Treatment is started and the patient responds as expected. This happens for many people, but not all.
In fact, a small, but significant number of cases do not fit this schematic for thyroid function tests . Sometimes patients have abnormal TSH and normal thyroid hormones, or abnormal thyroid hormones yet normal TSH. Another perplexing situation is a patient taking medication and their lab results still not normalizing. Establishing a correct diagnosis in these cases is critically dependent on careful clinical assessment, combined with other focused labs, radiological and genetic testing .
This topic is out of the scope of this article. Please click here for a detailed article on how to manage anomalous lab results.
Click to expand
 B. Brady, “EndocrineWeb,” endocrineweb, 07 Apr 2017. [Online]. Available: https://www.endocrineweb.com/conditions/thyroid-nodules/thyroid-gland-controls-bodys-metabolism-how-it-works-symptoms-hyperthyroi. [Accessed 12 July 2017].
 O. Koulouri, C. Moran, D. Halsall, K. Chatterjee and M. Gurnell, “Pitfalls in the measurement and interpretation of thyroid function tests,” Best Practice & Research. Clinical Endocrinology & Metabolism, vol. 27, no. 6, pp. 745-762, 2013. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857600/].
 B. Dong, “How medications affect thyroid function,” Western Journal of Medicine, vol. 172, no. 2, pp. 102-106, 2000. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070767/].
 M. Gurnell, D. Halsall and K. Chaterjee, “What should be done when thyroid function tests do not make,” Clinical Endocrinology, vol. 74, pp. 673-678, 2011. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2011.04023.x/abstract].
About the Author
I’m Johann de Chickera, a Naturopathic Doctor, practicing in Ontario, Canada. My clinical practice relies on keeping up with the most up-to-date research and continued education. This blog serves as a way to provide others with a compilation of everything I’ve learned along the way. Please click here if you’re local and want to see me in practice.