Unit Converter
Thyroxine (total T4)
(Major Thyroid Hormone - Reflects Secretory Capacity of the Thyroid Gland)
Synonyms
- Total T4
- Thyroxine
- TT4
- Serum thyroxine
- Protein-bound + free thyroxine
Units of Measurement
- nmol/L
- µg/dL
- µg/100 mL
- µg%
- ng/mL
- µg/L
Unit Conversions
Molecular Weight of Thyroxine (T4) = 776.87 g/mol
nmol/L ↔ µg/dL
1 µg/dL=12.87 nmol/L1\ \text{µg/dL} = 12.87\ \text{nmol/L}1 µg/dL=12.87 nmol/L 1 nmol/L=0.0776 µg/dL1\ \text{nmol/L} = 0.0776\ \text{µg/dL}1 nmol/L=0.0776 µg/dL
µg/dL ↔ ng/mL
1 µg/dL=10 ng/mL1\ \text{µg/dL} = 10\ \text{ng/mL}1 µg/dL=10 ng/mL 1 ng/mL=0.1 µg/dL1\ \text{ng/mL} = 0.1\ \text{µg/dL}1 ng/mL=0.1 µg/dL
µg/dL = µg/100 mL = µg%
ng/mL ↔ µg/L
1 ng/mL=1 µg/L1\ \text{ng/mL} = 1\ \text{µg/L}1 ng/mL=1 µg/L
Description
Total T4 (thyroxine) measures all circulating thyroxine, including:
- Protein-bound T4 (≈ 99.97%)
- Free T4 (≈ 0.03%)
Because T4 is strongly bound to thyroxine-binding globulin (TBG), total T4 levels depend on thyroid status + binding proteins.
Total T4 is still useful clinically but must be interpreted with:
- TSH
- TBG status
- Free T4 (preferred test in most scenarios)
Physiological Role
T4 is the major hormone secreted by the thyroid gland. Most T4 is converted in peripheral tissues to T3, the active form.
Functions:
- Regulates basal metabolic rate
- Influences growth & bone maturation
- Controls thermogenesis
- Modulates cardiovascular, neurological, and gastrointestinal systems
- Essential for fetal brain development
Clinical Significance
HIGH TOTAL T4
1. Hyperthyroidism
- Graves’ disease
- Toxic adenoma
- Toxic multinodular goiter
- Thyroiditis (early phase)
2. Excessive Thyroxine Intake
- Over-replacement therapy
- Factitious hyperthyroidism
3. Increased TBG Levels
(total T4 high but free T4 normal)
Occurs in:
- Pregnancy
- Estrogen therapy / OCPs
- Tamoxifen
- Cirrhosis
- Hereditary TBG excess
4. Drugs that Increase T4
- Methadone
- 5-FU
- Amiodarone (early)
LOW TOTAL T4
1. Primary Hypothyroidism
- Hashimoto thyroiditis
- Post-surgery
- Post-radioiodine therapy
2. Secondary Hypothyroidism
- Pituitary TSH deficiency
- Hypothalamic TRH deficiency
3. Low TBG Levels
(total T4 low but free T4 normal)
- Androgen therapy
- Nephrotic syndrome
- Severe liver disease
- Critical illness
- Hereditary TBG deficiency
4. Drugs that Decrease T4
- Phenytoin
- Carbamazepine
- Rifampin
- Glucocorticoids
Reference Intervals
(Tietz 8E + ATA + Mayo + ARUP)
Total T4
| Population | Reference Range |
| Adults | 65 – 170 nmol/L |
| (5 – 13 µg/dL) | |
| Children | Slightly higher upper range |
| Pregnancy (TBG ↑) | Total T4 increases by 1.5× of non-pregnant upper limit |
Critical Interpretation
- > 200 nmol/L ( > 15 µg/dL) → significant hyperthyroxinemia
- < 40 nmol/L ( < 3 µg/dL) → severe hypothyroidism
Diagnostic Uses
1. Evaluation of Suspected Hypothyroidism
Interpreted with TSH and FT4.
2. Evaluation of Hyperthyroidism
3. Assessment of TBG Abnormalities
If total T4 abnormal but FT4 normal.
4. Drug-induced Thyroid Disorders
Monitoring of:
- Amiodarone
- Antiepileptics
- Estrogen therapy
5. Pregnancy Thyroid Function Testing
Total T4 increases physiologically.
Analytical Notes
- TBG levels strongly affect TT4 readings.
- Free T4 by equilibrium dialysis or immunoassay is often preferred.
- Hemolysis may cause mild interference.
- Biotin supplements may interfere with some immunoassays.
Clinical Pearls
- Total T4 is unreliable alone because binding proteins vary widely.
- Always interpret TT4 with TSH ± FT4 for correct diagnosis.
- Normal total T4 does NOT exclude hypothyroidism if TBG is low.
- Pregnancy requires adjusting TT4 interpretation (1.5× rule).
- If TT4 is abnormal but FT4 normal → think TBG abnormalities.
Interesting Fact
More than 1000 molecules of T4 bind to every single molecule of TBG - making TBG the dominant determinant of total T4 concentration in blood.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Thyroid Hormones
- American Thyroid Association (ATA) Guidelines - Thyroid Disease
- AACE Thyroid Function Testing Guidelines
- Mayo Clinic Laboratories - Total T4
- ARUP Consult - Thyroid Function
- NIH / MedlinePlus - Thyroxine