If you’ve read Part 1 of my thyroid series, you’ll know that the thyroid hormone system is responsible for regulating a huge number of body processes, and that there is more to testing the intricate hormonal system of the thyroid than just getting a TSH and calling it a day. The more you start to dive into thyroid physiology – the triggers for thyroid hormone production and conversion, the receptivity of the tissues, and the dance between the brain, the thyroid gland, and the tissues – the more you realize it’s an incredible, intricate web.
I have posted before on how it’s possible to have low thyroid symptoms even when your TSH is normal. In that post, I alluded to the idea that it is totally possible (and not that uncommon) to have hyper- or hypo-thyroid-like symptoms with a TSH that falls in the middle of the normal range. I also mention the intricacies of TSH being a pituitary hormone that responds to levels of thyroid hormone in the brain; not always properly reflecting levels of thyroid hormone acting at the tissues and organs. But before I get ahead of myself, let me introduce you to the main players when it comes to thyroid testing.
TRH (thyrotropin releasing hormone): to activate thyroid hormone production, the body sends a message to the brain that it needs increased metabolism. The hypothalamus, a region of the brain responsible for monitoring messages from the nervous and endocrine systems, delivers a message to the pituitary (another brain region) via the chemical messenger TRH that metabolism should be increased.
TSH (thyroid stimulating hormone): in response to the hypothalamus, the pituitary gland then releases TSH, which talks directly to the thyroid gland itself. TSH causes iodine to enter the thyroid, and turns on an enzyme called thyroid peroxidase (TPO) that manufactures the thyroid hormones T4 and T3.
The more TSH that is released, the stronger the signal to turn up thyroid hormone production; the lower the TSH, the weaker the signal. Classically, when thyroid hormone production drops, TSH goes up (I like to think of it as the brain yelling at the thyroid for more hormone); and when thyroid hormone production goes up, TSH drops (to turn down the signal). I consider testing TSH a preliminary look at thyroid physiology, and always read the number with a grain of salt until I see further testing.
There’s actually a body of literature that has looked at the limited utility of TSH testing. Researchers state that the TSH is a poor measure for estimating the severity of thyroid failure; they have shown that TSH levels do not correlate well with tissue levels of thyroid hormone; and they’ve questioned the utility of TSH alone to monitor thyroid hormone replacement.
T4 (thyroxine): in response to TSH from the pituitary, the thyroid produces a protein called thyroglobulin. Thyroglobulin acquires iodine molecules to produce thyroid hormone T4 (named for its four molecules of iodine), and a little bit of T3 (named for its three molecules of iodine) in the thyroid gland, thanks to the action of TPO.
T4 is the predominant hormone produced by the thyroid gland – about 94% of what it releases is T4. T4 and T3 then bind to thyroid-binding proteins, as “bound” proteins, and shuttle through the bloodstream on their way to the tissues. They are released from binding proteins at the cells, after which they are referred to as “free” hormones.
In its “free” (unbound by a carrier molecule) form, T4 has no direct hormonal activity – it can bind to cell receptors at the tissues but causes no appreciable cellular effects. However, T4 can be converted by enzyme activity at the tissues into T3 (more on this below) – the activated version of thyroid hormone. Testing the level of free T4 tells us how much precursor thyroid hormone is actually circulating in the bloodstream.
T3 (triiodothyronine): as mentioned above, T3 is the active version of thyroid hormone and only constitutes about 6% of the total hormone the thyroid releases. As it is only produced in very small amounts by the thyroid itself, the majority of T3 is formed by enzymatic breakdown from T4 predominently in the liver, but also in heart, muscle and nerve cells. Some T4 is even made active in the intestines through the action of healthy probiotic bacteria. The enzyme that removes one molecule from T4 to make T3 is called tetraiodithyronine5’deiodinase (no test later, I promise). T3 hormone in its free (unbound by carrier molecule) form, binds to receptors on every single cell in the human body, and causes a variety of cellular changes. Testing levels of free T3 is the best way to determine how much free and active thyroid hormone is available to the tissues.
rT3 (reverse T3): interestingly, not all of the T4 that the thyroid produces is converted into active free T3. About 60% is converted down this classic route, and a small and variable amount is converted into reverse T3 (rT3) – this is molecule that looks a lot like T3, but like a key that fits a lock but won’t turn it, rT3 does not cause cellular activity when it binds to the receptors. Under cases of extreme stress such as major trauma, chronic illness, or severe chronic emotional stress, rT3 production is increased. There appears to be a link between high cortisol levels and high rT3. I’ll check a reverse T3 level in someone who has an extreme imbalance of the cortisol system, has a history of chronic stress, surgery or trauma, or if we're having trouble normalizing free T3 levels with conversion nutrients, herbs or hormones.
Thyroid antibodies: it is possible for the body to manufacture autoantibodies against various components of the thyroid hormone cascade. This means that the body’s immune system is attacking itself, and an autoimmune process is happening against the thyroid. This can result in either hypothyroidism, hyperthyroidism, or (commonly) fluctuations between both states, depending on the target of the antibodies and the amount of attack currently underway. Specific antibodies are helpful to diagnose Hashimoto’s (which classically presents hypothyroid) and Graves (which classically presents hyperthyroid) diseases.
A thyroid peroxidase antibody (TPO Ab) test is the most important diagnostic indicator of Hashimoto’s – TPO makes thyroid hormones T4 and T3, and is the most common target of the immune system in Hashimoto’s. Another test called thyroglobulin antibody (TG Ab) is often also done; thyroglobulin (the protein that forms as the base of T4 and T3) is another common target in Hashimoto’s.
A test for thyroid stimulating hormone antibodies (TSH Ab) is also called a TSI test (thyroid stimulating immunoglobulin), and is used to identify Grave’s disease (though TSI can also be elevated in Hashimoto’s). These test should be done periodically if they’ve shown positive in the past, and should still be tested even if they come up negative once or twice – because of fluctuations in the immune system, the amount of antibodies can fluctuate too. For example, avoiding gluten can seriously lower the TPO antibody levels. As soon as you’ve tested positive for thyroid antibodies, however, you have a confirmed autoimmune thyroid condition and the target of treatment is not just thyroid hormone, but treating the overactivation of the immune system.
I check TPO antibodies preliminarily in every thyroid workup - and always with those trying to conceive, as elevated TPO antibodies have been associated with a harder time getting pregnant. If there is a strong picture of autoimmunity present, especially if a patient's other thyroid markers like TSH are fluctuating up and down, I may also test TGAb or TSI.
The Bottom Line on Thyroid Testing
Since I’ve rambled for a few paragraphs about each of the most important components of your thyroid to get to know, I’d like to finish with a snapshot of how I test the thyroid with a new patient. Most of my patients come in with a TSH alone, and if I see any clinical signs of hypothyroidism, hyperthyroidism, or autoimmune thyroid I run a full thyroid panel +/- antibodies and reverse T3 (below).
Typically I do these tests on almost every fertility and suspected hypo- or hyper-thyroid patients: TSH
Free T4
Free T3
TPO antibodies
+/- TG and/or TSI antibodies (if there is a strong suspicion of autoimmune thyroid)
+/- reverse T3 (if there is a strong suspicion of chronic stress)
If you’ve only had a TSH done before, and you have any of the signs or symptoms of a thyroid disorder (see my first post here), you need more involved thyroid hormone testing. Ask your doc, your ND, or speak with me at Acubalance to get a closer look.
Thanks for reading! Hope you're looking forward to my next blog in this series – Part 3: essential nutrients for your thyroid.
In health,
Dr Kali MacIsaac HBSc, ND
Naturopathic Doctor
Previous post in this series: Thyroid Series Part 1: Your Thyroid 101
Next post in this series: Thyroid Series Part 3: Essential Nutrients For Your Thyroid