Examples of ECLIA and CLIA for Measuring Free Thyroxine (fT4) and Free Triiodothyronine (fT3)
Electrochemiluminescence Immunoassay (ECLIA) and Chemiluminescent Immunoassay (CLIA) are preferred methods for measuring free thyroid hormones due to their accuracy and reduced interference from autoantibodies compared to older radioimmunoassay techniques.
Comparison of ECLIA and CLIA Methods
ECLIA (Electrochemiluminescence Immunoassay)
- Specific Examples:
CLIA (Chemiluminescent Immunoassay)
- Specific Examples:
- Various automated direct one-step or two-step immunoassays using high molecular weight ligands or labeled antibodies 3
- Multiple commercial platforms from different manufacturers (specific brand names not mentioned in the evidence)
Performance Characteristics
Advantages of ECLIA over Traditional Methods
- ECLIA provides more accurate measurements in patients with triiodothyronine-binding autoantibodies compared to radioimmunoassay (RIA) 1
- In a study of patients with T3-binding autoantibodies, ECLIA measurements of fT3 produced values that correctly reflected the patients' thyroid status, while RIA showed spuriously high results 1
Limitations and Interferences
- Antiruthenium antibodies can cause interference in Roche ECLIA assays for TSH, fT4, and fT3 2
- Even the newer generation Roche fT4 assay still shows interference from antiruthenium antibodies 2
Clinical Applications
Diagnostic Utility
- Free hormone measurements (fT4 and fT3) have superseded total hormone determinations due to their higher diagnostic performance 3
- fT4 and fT3 measurements are particularly valuable when:
- Thyroid status is unstable (first months of treatment, altered L-T4 dose, subacute thyroiditis)
- Hypothalamic-pituitary function is disturbed (central hypothyroidism)
- TSH determination alone would be misleading 3
Monitoring Considerations
- For central hypothyroidism, the Endocrine Society recommends monitoring free T4 rather than TSH, targeting the upper half of the normal range 4
- When monitoring thyroid replacement therapy, free T4 levels should be used for patients with central hypothyroidism 4
Quality and Standardization Issues
Accuracy and Precision
- In a comparative study by the IFCC Working Group:
- For fT4: Only 2 of 15 immunoassays showed mean bias within 10% of the reference method
- For fT3: Only 4 of 13 immunoassays showed mean bias within 10% of the reference method
- Most assays showed negative biases up to -42% for fT4 and -30% for fT3 5
- Within-run imprecision ranged from 1.0% to 11.1% for fT4 and 1.8% to 9.4% for fT3 5
Reference Methods
- Equilibrium dialysis-isotope dilution-mass spectrometry (ED-ID-MS) is considered a reference method for free hormone measurements 5
- Direct equilibrium dialysis/RIA can be used for simultaneous measurement of fT4 and fT3 in undiluted serum 6
Clinical Pearls
- When interpreting thyroid function tests, it's essential to measure both TSH and free T4 simultaneously for accurate diagnosis 4
- In patients with suspected central hypothyroidism, free T4 measurement is more reliable than TSH 3
- When evaluating patients with non-thyroidal illness (NTI), be aware that while total T3 may be low, free T3 is often normal in approximately 83% of these patients 6
Remember that the choice between ECLIA and CLIA methods should consider potential interferences, particularly in patients with known autoantibodies to thyroid hormones.