Free T3

You're exhausted, gaining weight, always cold, and your brain feels like it's wrapped in cotton. Your doctor checks your thyroid. TSH comes back normal. "Your thyroid is fine," they say.

But is it?

Here's the gap most patients never learn about: your thyroid gland mainly produces T4, a storage hormone that must be converted into T3 before your cells can use it. Most doctors check only TSH and sometimes T4. But you can have a perfectly normal TSH and T4 while your body quietly fails to convert T4 into the hormone that actually runs your metabolism ^[1]. The raw material is there. The active product is not. And unless someone checks Free T3, this conversion problem is completely invisible.

Free T3 measures the fraction of active thyroid hormone actually available to your cells right now. It's the most direct window into your metabolic pace, and it's probably not on your standard blood panel.

T3 (triiodothyronine) is the active form of thyroid hormone. It enters your cells, binds to nuclear receptors, and directly controls how fast your metabolism runs: energy production, body temperature, heart rate, mental clarity, and fat burning.

But your thyroid mostly produces T4 (thyroxine), not T3. About 80% of your T3 comes from converting T4 in the liver, kidneys, and other tissues using enzymes called deiodinases ^[2]. Only about 0.3% of T3 in the blood is "free" (unattached to carrier proteins), and this free fraction is what actually enters cells and does the work.

This is why Free T3 matters: if your body cannot efficiently convert T4 to T3, you may have plenty of raw material but not enough active hormone. You will feel hypothyroid (fatigued, cold, foggy, gaining weight) even though your TSH and T4 look normal on paper.

T3 acts through nuclear thyroid hormone receptors (TR-alpha and TR-beta), which function as ligand-activated transcription factors. When T3 binds, it switches on genes involved in mitochondrial biogenesis, uncoupling protein expression (thermogenesis), Na+/K+-ATPase activity (resting energy expenditure), and LDL receptor expression (cholesterol clearance).

Peripheral T4-to-T3 conversion is catalyzed by type 1 deiodinase (D1, primarily in liver and kidney) and type 2 deiodinase (D2, in brain, pituitary, brown fat, and thyroid). A third enzyme, type 3 deiodinase (D3), inactivates T4 by converting it to reverse T3 (rT3), an inactive metabolite. All three deiodinases are selenoproteins requiring selenium as a cofactor.

In states of illness, inflammation, caloric restriction, and chronic stress, D1 activity decreases and D3 activity increases. This coordinated shift reduces T3 and raises rT3. The resulting "low T3 syndrome" (euthyroid sick syndrome) is an adaptive energy-conservation response, but when it becomes chronic it perpetuates fatigue, metabolic slowing, and cardiovascular risk ^{[3] [4]}.