Thyroid hormone transport and deiodinases !
- Mechanism
- For completeness
Almost all thyroid hormone travels attached to proteins; only a tiny free part works. Tissues turn T4 into the active T3 themselves.
Updated 2026-11-01
Also called: TBG, Free T4, Reverse T3, Deiodinases
See it in 3D: Thyroid gland · Liver · Pituitary gland
What it is
The thyroid secretes mostly T4, a prohormone, and a little T3. In blood more than 99% of both is bound to proteins, mainly thyroxine-binding globulin (TBG), transthyretin and albumin; only the free fraction enters cells and sets TSH. Inside tissues, deiodinase enzymes decide the hormone's fate: D1 and D2 activate T4 to T3, and D3 inactivates both. This explains why total T4 changes in pregnancy while the person stays euthyroid, and why T3 falls in severe illness.
How it works, step by step
- The thyroid releases T4 and T3 (ratio roughly 14–20 to 1) after cleaving thyroglobulin.
- In plasma they bind TBG, transthyretin and albumin; the bound pool is a buffer that releases free hormone as it is used.
- Free hormone enters cells through transporters (MCT8 and others), not just by diffusion.
- D1 (liver, kidney, thyroid) and D2 (brain, pituitary, brown fat, muscle) remove an outer-ring iodine: T4 → T3.
- D3 (brain, placenta, fetal tissues) removes an inner-ring iodine: T4 → reverse T3 and T3 → T2, both inactive.
- T3 binds its nuclear receptor with about tenfold more affinity than T4 and changes gene transcription.
- In fasting and severe illness D1 activity falls and D3 rises: T3 ↓, reverse T3 ↑, saving energy.
Hormone axes and feedback
Hypothalamic–pituitary–thyroid axisLesion None (normal)
Tap a box to see the hormone, or choose a lesion to see the lab pattern.
- Stimulates (+)
- Inhibits / negative feedback (−)
- Level ↑
- Level ↓
Approximate reference values (vary by laboratory)
| Parameter | Value | Note |
|---|---|---|
| Free T4 | ≈ 0.8–1.8 ng/dL | ≈ 10–23 pmol/L |
| Total T4 | ≈ 5–12 µg/dL | rises with TBG |
| Free fraction of T4 | ≈ 0.03% | |
| Half-life T4 / T3 | ≈ 7 days / ≈ 1 day |
Approximate values for a healthy adult at rest; each laboratory sets its own ranges.
Deiodinases
| Enzyme | Main sites | Reaction | Role |
|---|---|---|---|
| D1 | Liver, kidney, thyroid | T4 → T3; clears rT3 | Plasma T3; inhibited by propylthiouracil |
| D2 | Pituitary, brain, brown fat, muscle | T4 → T3 (inside the cell) | Local T3; mediates TSH feedback |
| D3 | Placenta, brain, fetal tissue | T4 → rT3; T3 → T2 | Inactivation; protects the fetus |
Clinical notes
- Pregnancy: estrogen raises TBG, so total T4 rises about 1.5-fold; free T4 is the useful test (and trimester-specific ranges are used).
- Nonthyroidal illness (sick euthyroid): low T3, high reverse T3, normal or low TSH; it is not treated as hypothyroidism.
- Large infantile hemangiomas can express D3 and cause consumptive hypothyroidism.
- MCT8 transporter defects (Allan–Herndon–Dudley syndrome): high T3 in blood but brain hypothyroidism with severe neurodevelopmental delay.
Test yourself
Think of the answer, then tap the question to see it.
A woman on oral estrogen has high total T4 and normal TSH. Is she hyperthyroid?
No. Estrogen raises TBG, so more T4 is bound and total T4 rises; free T4, which sets TSH, stays normal.
Why does TSH follow free T4 closely even though T3 is the active hormone?
Pituitary thyrotrophs use D2 to convert T4 into T3 inside the cell, so their feedback signal depends on the free T4 supply.
Why is reverse T3 high in a patient in the ICU?
Severe illness lowers D1 activity (less T4 → T3 and less rT3 clearance) and raises D3 (more T4 → rT3).
Why does T4 have a much longer half-life than T3?
T4 binds TBG with higher affinity, so a smaller free fraction is available for uptake and degradation.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Actions of thyroid hormones
- The thyroid axis: reading TSH and free T4
- Maternal physiological changes in pregnancy
- The endocrine stress response
- Hormones: types, receptors and feedback
Related conditions
In Biochemistry
- Iodothyronine deiodinases (DIO1, DIO2, DIO3)
- Transthyretin (prealbumin)
- Thyroxine (T4)
- Triiodothyronine (T3)
- Thyroid hormone synthesis
- Nuclear receptors
In Pharmacology
Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.
Sources: 17.4 The Thyroid Gland (OpenStax (Rice University), 2022); Hypothyroidism (StatPearls (NCBI Bookshelf), 2024); Anatomy, Head and Neck, Thyroid (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 77). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).
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Representative model, for educational purposes only.