Thyroid Serie Article 2: Inside the Thyroid — How T3 and T4 Are Made (and What Can Disrupt the Process)

Your thyroid is a butterfly-shaped gland sitting snugly at the base of your neck, and it plays a powerful role in controlling metabolism, temperature, mood, and energy levels. But how does this small gland actually make the hormones that influence nearly every cell in your body?

The production of thyroid hormones is a multi-step biochemical dance, requiring the right signals, building blocks, enzymes, and nutrients. Let’s take a step-by-step look into this intricate process — and the many places it can go wrong.

🧪 The Raw Materials: Tyrosine + Iodine

Thyroid hormones are made from two main ingredients:

  • Tyrosine: An amino acid (from protein) that forms the backbone of thyroid hormones.

  • Iodine: A trace mineral that's essential for hormone synthesis. It provides the "I" in T3 (triiodothyronine) and T4 (thyroxine), referring to the number of iodine atoms.

But how are these two combined into powerful messengers like T3 and T4?

⚙️ The Assembly Line: Step-by-Step

  1. Thyroglobulin (Tg) Production

    • Inside the thyroid cells, the body produces thyroglobulin, a large protein made from tyrosine.

    • Thyroglobulin acts like a scaffold that holds tyrosine units in place for iodine to attach.

  2. Iodide Oxidation by TPO

    • Iodine enters the thyroid in the form of iodide (I⁻).

    • An enzyme called Thyroid Peroxidase (TPO) — with help from hydrogen peroxide (H₂O₂) — oxidizes iodide into iodine (I), its active form.

    • TPO then adds iodine to tyrosine units on thyroglobulin, creating:

      • MIT (Monoiodotyrosine) – 1 iodine attached

      • DIT (Diiodotyrosine) – 2 iodines attached

  3. Hormone Formation via Conjugation

    • TPO catalyzes the fusion of iodinated tyrosines:

      • T4 = DIT + DIT (4 iodine atoms)

      • T3 = MIT + DIT (3 iodine atoms)

      • rT3 (reverse T3) = DIT + MIT (also 3 iodine atoms, but inactive)

🧠 T4 is the main hormone produced (~90%), but T3 is the biologically active one. A small portion becomes reverse T3 (rT3) — an inactive form that acts like a hormonal brake.

🧬 Genes Involved in This Process

Several genes can affect how efficiently this production line runs:

  • TG (Thyroglobulin)

    • SNPs (e.g., rs2076740) can impair the structure or production of thyroglobulin, increasing risk for goiter, thyroid dyshormonogenesis, or autoimmunity (like Graves’ or Hashimoto’s).

  • TPO (Thyroid Peroxidase)

    • Targeted in Hashimoto’s. Autoantibodies to TPO can block iodine incorporation and impair hormone production.

  • GPX1 (Glutathione Peroxidase)

    • Protects the thyroid by detoxifying hydrogen peroxide (H₂O₂), which is a necessary but potentially damaging byproduct.

    • SNP rs1050450 (Pro198Leu): lower activity may impair this defense, increasing oxidative damage and Hashimoto’s risk.

🧂 Nutrients That Make or Break It

Hormone production relies on a few critical cofactors:

  • Iodine

    • Needed for hormone synthesis. But too little = deficiency, and too much = autoimmune risk, especially if selenium is lacking.

  • Selenium

    • Supports GPX1 and DIO enzymes (involved in T4-to-T3 conversion). Without it, oxidative damage and rT3 production increase.

  • Iron & Zinc

    • Help TPO and TRH signaling, and support thyroid receptor sensitivity.

  • Glutathione

    • Antioxidant that protects the thyroid from hydrogen peroxide buildup.

☢️ Disruptors of Thyroid Hormone Synthesis

This process is delicate — and vulnerable to disruption:

  • Goitrogens: Foods like soy, broccoli, kale, and spinach contain compounds that can block iodine uptake if eaten in excess (especially raw).

  • Environmental Toxins:

    • Chlorine and fluoride compete with iodine for absorption.

    • BPA, pesticides, and heavy metals can interfere with thyroid enzyme activity.

  • Cortisol: Chronic stress (and high cortisol) can blunt TSH production and inhibit conversion to active T3.

  • Autoantibodies: In Hashimoto’s, the immune system targets TPO and thyroglobulin, destroying the hormone-making machinery.

📉 Symptoms When This Process Fails

When your thyroid can't properly produce or activate hormones, symptoms start to appear:

  • Too little T4 or T3: fatigue, cold sensitivity, depression, weight gain, dry skin, brain fog.

  • Too much T4/T3: anxiety, insomnia, heart palpitations, weight loss, heat sensitivity.

  • Too much rT3: sluggishness, stress sensitivity, hormonal resistance.

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