What is the accuracy of free Triiodothyronine (T3) measurement?

Accuracy of Free T3 Measurement

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is significantly more accurate than immunoassay methods for measuring free T3, especially at low concentrations where immunoassays frequently misclassify results as normal when they are actually below reference range. 1

Measurement Methods and Their Accuracy

Gold Standard Method

• Equilibrium dialysis/radioimmunoassay (RIA) is considered the reference method for free hormone measurements, providing the most reliable results for free T3 2, 3
• Direct measurement by equilibrium dialysis is particularly important when accuracy is critical for clinical decision-making 3

Immunoassay Limitations

• At T3 concentrations between 50-113 ng/dL, immunoassay methods significantly overestimate values compared to LC-MS/MS 1
• 45% of patients classified as having normal T3 levels by immunoassay were actually below the 2.5th percentile when measured by LC-MS/MS 1
• Immunoassay correlation with TSH is inferior to LC-MS/MS measurements, potentially leading to inappropriate clinical decisions 1

Mass Spectrometry Advantages

• LC-MS/MS offers higher specificity and improved accuracy for hormone measurement 1, 4
• LC-MS/MS is less susceptible to interferences from binding protein abnormalities and other conditions that affect immunoassay results 4
• The correlation between immunoassay and LC-MS/MS is particularly poor at the extremes of the measurement range (r=0.51-0.75), precisely where accurate measurement is most clinically important 4

Clinical Implications

Impact on Patient Management

• Inaccurate free T3 measurement can affect treatment decisions, particularly regarding whether to use T4 monotherapy or combination T4/T3 therapy 1
• In patients with hypothyroid symptoms and normal T4 but low T3 by LC-MS/MS (but normal by immunoassay), T3 supplementation might be warranted but missed if relying on immunoassay results 1

Special Populations

• Free T3 measurement accuracy is particularly important in:
  • Severe non-thyroidal illness patients with low serum thyroxine binding capacity 2
  • Patients with unstable thyroid status (first months of treatment, altered L-T4 dose) 2
  • Patients with hypothalamic-pituitary disturbances where TSH is unreliable 2

Recommendations for Clinical Practice

• When accurate free T3 measurement is critical, request LC-MS/MS or equilibrium dialysis methods rather than standard immunoassays 1, 4
• Be particularly cautious of immunoassay results in the low-normal range, as these may actually represent true low values when measured by more accurate methods 1
• Consider the clinical context when interpreting free T3 results, especially in hospitalized patients where the correlation between thyroid hormones and TSH is often disrupted 4
• In cases where hypothyroid symptoms persist despite normal T4 and "normal" T3 by immunoassay, consider confirming with LC-MS/MS before ruling out T3 deficiency 1

Common Pitfalls to Avoid

• Relying solely on immunoassay results for free T3, especially when values are in the low-normal range 1
• Failing to consider the measurement method when interpreting free T3 results 1, 4
• Assuming that normal free T3 by immunoassay excludes T3 deficiency, particularly in symptomatic patients 1
• Not recognizing that the correlation between free T3 and TSH is often poor in hospitalized patients, limiting the utility of these measurements for diagnosis in this population 4