Unit Converter
Thyroxine-binding globulin (TBG)
(Primary Transport Protein for T4 & T3 - Major Determinant of Total Thyroid Hormone Levels)
Synonyms
- TBG
- Thyroxine-binding globulin
- Serpin A7 (gene name)
- Thyroid hormone–binding globulin
- T4/T3 transport protein
Units of Measurement
- nmol/L
- mg/L
- mg/dL
- mg/100 mL
- mg%
- µg/mL
Unit Conversions
Molecular Weight of TBG ≈ 54,000–58,000 Da (~56 kDa)
nmol/L → mg/L
1 nmol/L=0.056 mg/L1\ \text{nmol/L} = 0.056\ \text{mg/L}1 nmol/L=0.056 mg/L 1 mg/L=17.8 nmol/L1\ \text{mg/L} = 17.8\ \text{nmol/L}1 mg/L=17.8 nmol/L
mg/dL → mg/L
1 mg/dL=10 mg/L1\ \text{mg/dL} = 10\ \text{mg/L}1 mg/dL=10 mg/L
mg% = mg/dL
µg/mL → mg/L
1 µg/mL=1 mg/L1\ \text{µg/mL} = 1\ \text{mg/L}1 µg/mL=1 mg/L
Description
Thyroxine-binding globulin (TBG) is the major transport protein for thyroid hormones in serum:
- Binds ~75% of circulating T4
- Binds ~70% of circulating T3
The rest is carried by:
- Transthyretin (TTR)
- Albumin
TBG levels significantly affect total T4 and total T3, but do not change free hormone levels (FT4, FT3).
Therefore, changes in TBG can mimic thyroid disease unless interpreted correctly.
Physiological Role
- Carries & stabilizes T4/T3 in circulation
- Provides a hormone reservoir
- Maintains consistent delivery of thyroid hormone to tissues
Only free hormone is biologically active; TBG-bound hormone is inactive but essential for transport.
Clinical Significance
ELEVATED TBG
(High binding → high total T4/T3, normal FT4/FT3)
Causes of High TBG
1. Pregnancy
↑ Estrogen → ↑ TBG synthesis
2. High-Estrogen States
- Oral contraceptives (OCPs)
- Hormone replacement therapy
- Tamoxifen
- SERMs
3. Genetic TBG Excess
X-linked - heterozygous females mildly elevated, males high.
4. Hepatitis / Liver Disease (early)
Increased hepatic synthesis.
5. Medications
- Methadone
- Fluorouracil
6. Neonates
Naturally higher due to immature hepatic clearance.
Effect on Thyroid Tests
- Total T4 and T3: High
- Free T4/T3: Normal
- TSH: Normal
Important: Does NOT indicate hyperthyroidism.
LOW TBG
(↓ binding → low total T4/T3, normal FT4/FT3)
Causes
1. Androgen Therapy
Reduces TBG synthesis.
2. Nephrotic Syndrome
Loss of TBG in urine.
3. Severe Liver Failure
Reduced synthesis.
4. Acute Illness / NTIS
5. Genetic TBG Deficiency
X-linked recessive
- Partial or complete deficiency
- Very low total T4/T3
- FT4 & TSH normal
6. Medications
- Glucocorticoids
- Danazol
- Phenytoin
- Carbamazepine
- High-dose aspirin
Effect on Thyroid Tests
- Total T4 and T3: Low
- Free T4/T3: Normal
- TSH: Normal
Important: Does NOT indicate hypothyroidism.
Reference Intervals
(Tietz 8E + Mayo + ARUP)
Serum TBG
- 260 – 390 nmol/L
or - 15 – 25 mg/L
(assay-dependent; ranges may vary slightly)
High TBG
400 nmol/L → high-binding state
Low TBG
< 200 nmol/L → low-binding state
Diagnostic Uses
1. Evaluate Abnormal Total T4/T3 with Normal TSH
- Distinguish binding-protein abnormalities from real thyroid disease.
2. Pregnancy Thyroid Function Assessment
Total T4 and T3 increase because of TBG.
3. Investigating Suspected Genetic TBG Disorders
4. Differentiation of NTIS (Non-thyroidal Illness)
Useful when interpreting low total T4/T3.
5. Monitoring Liver or Renal Disorders
Analytical Notes
- Measured by immunoassay (RIA, CLIA, ELISA).
- TBG variants (genetic) may cause assay underestimation or overestimation.
- Check for biotin interference in streptavidin-based assays.
- Interpretation must be paired with free T4, free T3, and TSH.
Clinical Pearls
- Total T4 is meaningless without knowing TBG status.
- In pregnancy, total T4 rises by 1.5× — FT4 is preferred.
- Low TBG can mimic hypothyroidism if only total T4 is checked.
- High TBG can mimic hyperthyroidism.
- If total T4/T3 abnormal but TSH normal — ALWAYS measure TBG.
Interesting Fact
TBG has the highest affinity for thyroid hormones among all carrier proteins, but the lowest concentration, making it the key regulator of total hormone levels.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Thyroid Binding Proteins
- ATA Guidelines - Thyroid Function Testing
- AACE Thyroid Disorders Guidelines
- Mayo Clinic Laboratories - TBG
- ARUP Consult - Thyroid Binding & Transport Proteins
- NIH / MedlinePlus - Thyroid Tests