5'-Deiodinase and T4 → T3 Conversion
Definition
5’-Deiodinase is the enzyme that converts T4 (inactive·precursor) to T3 (active). 80% of the T4 secreted by the thyroid is converted to T3 in peripheral tissues (liver·kidney·muscle·brain). Selenium and zinc are cofactors. Even with normal T4, weak conversion is the core mechanism of clinical hypothyroidism.
5’-Deiodinase and T4 → T3 conversion
Thyroid hormone production·distribution:
- Thyroid secretes T4 80%, T3 20%
- T4 commonly mistaken as active — actually inactive·precursor
- All target action is via T3 (active form)
- T4 → T3 conversion determines 80% of thyroid hormone action
T4 vs T3 comparison:
| Marker | T4 (thyroxine) | T3 (triiodothyronine) |
|---|---|---|
| Thyroid secretion | 80% | 20% |
| Activity | Inactive·precursor | Active form |
| Action strength | Low | 4x T4 |
| Half-life | 7 days | 1~2 days |
| Test priority | TSH·free T4 | free T3·rT3 |
5’-Deiodinase 3 isoforms:
| Isoform | Location | Role |
|---|---|---|
| D1 | Liver·kidney·thyroid | T4 → T3, blood T3 supply |
| D2 | Brain·pituitary·brown fat | Tissue-internal T3, fine modulation |
| D3 | Placenta·brain·skin | T3 → T2 (inactivation), protective |
Reverse T3 (rT3) — conversion weakness marker:
- Iodine removed from different position on T4 → rT3
- rT3 is inactive·no cellular action
- Chronic stress·fasting·infection raise rT3
- T3/rT3 ratio is direct conversion efficiency marker
Mechanism — selenium·zinc dependence
1. Selenium — absolutely essential cofactor:
- 5’-deiodinase enzyme active site contains selenocysteine (Sec)
- Selenium deficiency → enzyme activity ↓ → T4 → T3 conversion weakened
- Selenium supplementation → active T3 +22%
2. Zinc — enzyme cofactor:
- 5’-deiodinase cofactor
- Supports TSH·thyroid hormone receptor binding
- Deficiency weakens conversion
3. Other cofactors:
- Iron (ferritin): supports thyroid hormone synthesis·conversion
- Vitamin A: thyroid hormone receptor support
- B12: indirect conversion support
- Glutathione: enzyme reduction environment
4. Causes of conversion weakness:
- Selenium·zinc·iron deficiency: most common
- Chronic stress·cortisol: rT3 ↑
- Fasting·dietary restriction: adaptive mechanism reduces conversion
- Chronic infection·inflammation: cytokines block conversion
- Liver·kidney disease: D1 activity ↓
- Carnitine deficiency: mitochondrial inefficiency
- Iodine excess/deficiency: variable response
Clinical relevance
1. Normal T4 + clinical hypothyroidism = conversion weakness:
- Routine tests measure only TSH·free T4 — not T3·rT3
- Patient: chronic fatigue·depression·cognitive decline·weight gain·cold sensitivity
- Doctor: “TSH·T4 normal, you’re fine”
- Reality: T3 deficiency or rT3 ↑ → clinical hypothyroidism
- Additional tests: free T3·rT3·T3/rT3 ratio
2. T4 vs T3 prescription:
- Standard hypothyroid prescription: levothyroxine (synthetic T4) first-line
- But conversion-weak patients show poor T4 monotherapy response
- T3 prescription (liothyronine, desiccated thyroid) or T4+T3 matrix
- Some clinical validation in US·EU for T4+T3 matrix
3. Selenium·zinc supplementation trials:
- 12 weeks selenium + zinc → T3/T4 ratio +28%
- Targets conversion not visible on routine testing
- Matrix superior to singles
Nutrient·natural molecule support
Selenium:
- Target: 200μg/day (Korean diet average 50~70μg, supplementation recommended)
- Diet: 1~2 Brazil nuts, tuna, fish
- Form: selenomethionine (superior absorption)
Zinc:
- Target: 30mg/day
- Diet: oysters, beef, pumpkin seeds
- Form: bisglycinate (superior absorption)
Iron·ferritin:
- Target: ferritin 50ng/mL+
- Diet: red meat, spinach
- Anemia assessment
Vitamin A:
- Target: 700~900μg RAE/day
- Diet: carrots, pumpkin, liver
Stress·cortisol management:
- Chronic stress raises rT3
- Sleep, adaptogens, meditation
Cautions
- Hyperthyroidism·Graves’: conversion acceleration target inappropriate. Physician assessment
- Selenium·zinc overdose: 400μg+ selenium = selenosis, 40mg+ zinc = copper deficiency
- Autoimmune thyroid·Hashimoto’s: selenium first, conservative on iodine
- Drug interactions: 4-hour separation from levothyroxine·methimazole
- Pregnancy·lactation: selenium 60
70μg, zinc 1113mg, physician assessment - Conversion weakness diagnosis: free T3·rT3 testing physician assessment
- 3~6 month cumulative assessment: thyroid hormone cycle is cumulative
Frequently asked questions
Q. My T4 is normal but I have hypothyroid symptoms?
A. Conversion weakness possible. Order free T3·rT3 testing. Low T3/rT3 ratio or high rT3 indicates conversion target. Selenium + zinc + iron·ferritin assessment first step.
Q. Do routine TSH·T4-only tests miss conversion weakness?
A. Yes. With clear clinical symptoms but normal TSH·T4, additional free T3·rT3 testing needed. Conversion-weak patients commonly receive normal verdicts on routine testing.
Q. How do selenium and zinc support conversion?
A. Selenium activates the selenocysteine in 5’-deiodinase, zinc as cofactor. Deficiency → enzyme activity ↓ → conversion weakened. Matrix supplementation 12 weeks → T3/T4 ratio +28%.
Q. Is T4+T3 matrix prescription better?
A. Some clinical effect for conversion-weak patients. But T3 has short half-life, higher side-effect risk, conservative prescription. Physician coordination needed. Selenium·zinc supplementation is first-line for natural conversion support.
Q. Are selenium·zinc sufficient in Korean diets?
A. Selenium: average 5070μg (RDA 55μg, borderline). 12 Brazil nuts/day sufficient. Zinc: average 810mg (RDA 811mg, sufficient). Oysters·beef·pumpkin seeds rich.