Understanding Thyroid Metabolism: A Complete Guide

Dr. Stengler: Have you ever wondered why your thyroid medication doesn't seem to be working? Your doctor prescribed thyroid hormone replacement, but you still feel tired, your metabolism is slow, you feel chilly, your sleep isn't good, your skin is dry, your joints ache, and your cognitive function isn't great. You're thinking: I'm on thyroid replacement because my labs showed hypothyroidism, but I still have these symptoms. Maybe not as bad as before, but not back to where I used to feel. And your doctor checks your TSH and free T4, says the levels look fine, and keeps the dose where it is. You're frustrated and wondering why the symptoms aren't going away.

There could be a very specific reason — and it comes down to the genetics of thyroid metabolism.

Let's quickly review: the thyroid gland, that butterfly-shaped gland in the neck below the Adam's apple, produces two main thyroid hormones — T4 and T3. It produces mostly T4, with a smaller amount of T3. In the body, T4 is converted by the liver and kidneys into the more active T3. While cell receptors can receive both T4 and T3, it's primarily T3 that enters the cell, acts on our genes, and produces the benefits we want — improved metabolism, better energy, and all the rest.

Here's the key: almost half the population has a genetic variation — also known as a single nucleotide polymorphism, or SNP — that makes them more likely to have problems converting T4 into T3. Given that thyroid medications are among the most commonly prescribed in America and around the world, that means millions of people may be genetically predisposed to poor T4-to-T3 conversion. There are other contributing factors too — selenium deficiency, imbalanced hormones like elevated cortisol from high stress — but the genetic factor is significant and often overlooked.

This is why it's so important to have your T3 levels tested — both total T3 and free T3. Most doctors don't check T3 levels, so you may never know if your levels are low-normal, below normal, or deficient. This can explain why your symptoms aren't fully resolving.

If T3 is the issue, a doctor can prescribe T3 therapy. The standard pharmaceutical form is called Cytomel, also known as liothyronine, available at regular pharmacies. Compounding pharmacies also carry T3, and I generally prefer them because they can formulate it in a sustained-release form. Regular T3 enters the system quickly and leaves quickly — within about three to four hours, much of it is already gone. Sustained-release T3 stays in the system longer, providing more consistent support for metabolism, energy, cognitive function, and other thyroid-dependent processes throughout the day.

If you're struggling with your thyroid medication and still have symptoms, look into the T3 conversion issue — it may very well be the missing piece. For more videos on thyroid and other hormone balance topics, visit my YouTube channel.

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