Low T3, Normal TSH, and Low Thyroid Symptoms: What’s Really Going On
Low T3, Normal TSH, and Thyroid Function
If you've been told your thyroid labs are "normal" but you’re still experiencing all the symptoms of low thyroid, several really important somethings are missing from that conversation:
TSH is not an indicator of thyroid function.
TSH is made by the pituitary (a gland that sits in the brain) and gives essentially no information about the actual state of thyroid function. We’re going to put a pin in this and circle back later.
The thyroid gland itself secretes primarily T4 thyroid hormone. T4 is a prohormone.
Once T4 is taken up by the cells of the body, it can be converted (metabolized) down one of two pathways. And, this is where things get interesting.
T3 vs Reverse T3: An Alice in Wonderland Story
Remember the mushroom in Alice in Wonderland?
The Caterpillar tells Alice that one side will make her tall and the other side will make her small.
Thyroid hormone metabolism is a bit like that mushroom.
T4 can be converted into T3 (triiodothyronine), considered the “active” form of thyroid hormone that increases metabolism.
T4 → T3 → more thyroid hormone signaling → more energy production (pro-metabolic)
T4 can also be converted into reverse T3 (rT3) — widely considered an inactive metabolite.
T4 → reverse T3 → energy conservation (widely considered anti-metabolic)
One pathway favors energy production. The other favors energy conservation bringing us right back to my main premise… symptoms show up when the body’s ability to make energy goes down.
How do your cells decide whether to convert T4 to T3 or reverse T3?
Your body uses enzymes called deiodinase enzymes to direct conversion of T4 down the energy producing or energy conserving pathway.
There are three of these enzymes: D1, D2 and D3. With regards to T4:
D1 is capable of converting T4 into either active T3 or reverse T3. Contributes more to circulating levels of T3 in the blood stream.
D2 converts T4 into active T3. Largely local (within the tissue of origin) effect.
D3 converts T4 into reverse T3. Contributes more to circulating levels of reverse T3 in the blood stream.
Here’s the thing…
Different tissues express different ratios of these three deiodinase enzymes.
Expression is impacted by stress (undereating, inflammation, psychological stress).
Some tissues are impacted more than others by stress.
Why does this matter?
Low or Normal TSH and Raging Low Thyroid
The thyroid’s signal to create thyroid hormone starts in the brain. Specifically, the hypothalamus, a gland in the mid-brain that regulates all hormone axes in the body. The simple sequence is this:
TRH (made by the hypothalamus) tells the pituitary to secrete TSH, which tells the thyroid to make thyroid hormone.
The hypothalamus gland rely heavily on local deiodinase 2 (D2) activity to convert T4 into T3. As long as T4 production by the thyroid is sufficient (or even insufficient, remind me to tell you about my own two year struggle to get a diagnosis of Hashimoto’s thyroiditis sometime), the thyroid will continue to make T3. In times of chronic stress… particularly due to inflammation, or calorie deficit:
Tissues like the liver (considered one of the main organs that helps keep circulating levels of T3 in the bloodstream “in range”) downregulate D1 (the enzyme that converts T4 into T3) and upregulate D3 (the enzyme that converts T4 into reverse T3) shifting the conversion pathway of T4 to reverse T3 placing the body into energy-conservation mode.
The hypothalamus, however, increases local D2 activity (the enzyme that converts T4 into T3 and because of where this enzyme sits in the cell, keeps that T3 inside the cell for much longer than either D1 or D2). This means that TSH (the hormone most practitioners actually measure) can be normal (or even low) while you’re struggling with functionally low thyroid.
Result? You get gaslighted into believing nothing’s wrong when how well your body’s actually using thyroid hormone (T4) isn’t even being measured!
From a lab standpoint, you have no total T3, free T3, or reverse T3 values to look at (or even total and free T4 values most of the time). Now, I get piping mad about a lot of things that way too many of us are gaslighted into believing about our bodies and this is one of them. As I’m typing this, I’m kind of worried about breaking the keyboard.
And, then… symptoms get worse.
As if the weight gain, and the brittle hair/hair loss, and the adult acne, and the dry legs, and the missing libido, and the teeth grinding and poor sleep, and the weird cycles and the low appetite and the bloating after eating and the exercise intolerance weren’t enough…
Suddenly you start feeling like you can’t get enough air on your daily walk.
Or, you get diagnosed with low thyroid and placed on replacement thyroid hormone and BAM! Now you’re reacting to breakfast.
When Low Thyroid Crosses the line into Dysautonomia and MCAS
This is where the thyroid conversation gets a lot more interesting.
Low T3 doesn't necessarily stay neatly contained inside the list of symptoms we've been taught to associate with hypothyroidism.
For me, it looked like air hunger, exercise intolerance, histamine reactions, recurrent UTI symptoms (without infection), and a seeming inability to control my body temperature (and eventually orthostatic headaches).
That overlap between thyroid function, MCAS, POTS and dysautonomia deserves its own conversation. I unpack that physiology here:
If you found this article outside of Follow the Physiology, this is just one piece of the larger conversation we're having there.
Start Follow the Physiology from the beginning →
→ MCAS
