Transthyretin – physiology and clinical significance
Transthyretin is a low molecular weight transport protein that is synthesized mainly in hepatocytes and in the choroid plexus of the central nervous system. In plasma, transthyretin functions as a carrier of thyroxine (T4) and also forms a stable complex with retinol-binding protein, which enables the transport of vitamin A. Due to its short biological half-life, approximately 48 hours, transthyretin quickly reflects changes in liver protein synthesis.
Regulation of serum concentration
The serum concentration of transthyretin is influenced by several simultaneous mechanisms, including the synthetic capacity of the hepatocyte, the body's energy balance and inflammatory activity. Transthyretin is classified as a negative acute phase protein and its synthesis is downregulated in inflammatory conditions by cytokine influence, primarily via interleukin-6. This means that reduced levels can occur even with adequate nutritional intake.
In catabolic states, starvation or fasting, transthyretin concentrations often drop within a few days, making the marker more sensitive than albumin to short-term changes in protein synthesis. In cases of reduced liver cell mass, for example in advanced liver disease, an early decline in transthyretin levels is seen, often in parallel with decreased prothrombin levels.
Reference range for S-transthyretin
| Age | Reference value | Unit |
|---|---|---|
| Adults | 0.20 – 0.40 | g/L |
| 0–14 days | < 0.11 | g/L |
| 15 days – < 1 year | 0.04 – 0.24 | g/L |
| 1 – < 5 years | 0.11 – 0.23 | g/L |
| 5 – < 13 years | 0.13 – 0.26 | g/L |
| 13 – < 16 years | 0.17 – 0.31 | g/L |
| Girls 16 – < 19 years | 0.16 – 0.33 | g/L |
| Boys 16 – < 19 years | 0.20 – 0.35 | g/L |
Interpretation in clinical context
Low levels of S-transthyretin occur in protein–energy malnutrition, catabolism, inflammatory conditions and liver disease. In the presence of concomitant inflammation, an isolated decrease in transthyretin cannot be interpreted as an expression of nutritional deficiency but must be evaluated together with acute phase reactants, especially CRP. In hyperthyroidism, decreased levels are often seen as a result of increased hormonal turnover and altered protein metabolism.
In chronic liver disease, transthyretin decreases early in the course of the disease and can be used as an indicator of reduced synthesis capacity. Unlike albumin, whose half-life is approximately 20 days, transthyretin provides a more dynamic picture of the liver's current protein synthesis. Elevated levels of S-transthyretin are uncommon and in most cases lack clinical relevance.
Limitations and differential diagnosis
S-transthyretin is not an isolated nutritional marker and should not be used independently for assessing nutritional status. The marker is affected by inflammation, hormonal status and liver function, which requires simultaneous clinical assessment and complementary laboratory analyses. In clinical practice, transthyretin is therefore used as a complement to albumin, prothrombin, CRP and clinical nutritional assessments.