Comparison of methods for measuring free thyroxin in nonthyroidal illness

Area of Science:

• Endocrinology
• Clinical Chemistry
• Laboratory Medicine

Background:

• Severe nonthyroidal illness (NTI) is often associated with altered thyroid hormone levels, including decreased thyroxine (T4) and free T4 (FT4).
• Tumor necrosis factor-alpha (TNF-alpha) may be elevated in NTI patients.
• Accurate measurement of FT4 is essential for diagnosing thyroid dysfunction, but NTI can interfere with assay performance.

Purpose of the Study:

• To evaluate the performance of four commercial free thyroxine (FT4) assays in patients with severe nonthyroidal illness (NTI).
• To compare FT4 measurements across different assay methods and with thyroid hormone levels in euthyroid and hypothyroid subjects.
• To assess the utility of the free thyroxine index (FTI) in NTI patients.

Main Methods:

• Four commercial FT4 assays (Abbott IMx, Amersham Amerlex MAB, Nichols, and Diagnostic Products Corporation (DPC) RIA) were evaluated.
• TNF-alpha was measured using a separate assay.
• Samples from 41 NTI patients, 24 euthyroid controls, and 10 hypothyroid patients were analyzed. The Abbott IMx method was also used to measure FTI.

Main Results:

• NTI patients exhibited subnormal FT4 levels in 61% (DPC), 29% (Amerlex), and 2.4% (Nichols) of cases.
• The DPC, Amerlex, and Abbott IMx methods yielded significantly lower FT4 values in NTI patients compared to controls.
• FTI correlated poorly with FT4 in NTI patients, unlike in euthyroid and hypothyroid groups. Abbott IMx and Nichols RIA showed minimal results in the hypothyroid range for NTI patients.

Conclusions:

• Commercial FT4 assays demonstrate considerable variability in performance when measuring FT4 in NTI patients.
• The DPC and Amerlex methods frequently misclassify NTI patients as hypothyroid.
• FTI is not a reliable indicator of thyroid status in NTI patients due to poor correlation with FT4.