Analytic measurements of free thyroxine

Area of Science:

• Endocrinology
• Clinical Chemistry
• Assay Development

Background:

• The clinical utility of free thyroid hormone (TH) determinations is debated, particularly concerning the free hormone hypothesis.
• Current analytical methods for free TH assays raise concerns about their reliability and accuracy in various clinical conditions.
• The validity of the free hormone hypothesis remains a contentious issue among endocrinologists.

Purpose of the Study:

• To clarify uncertainties surrounding the clinical use of free TH determinations.
• To critically assess the analytical validity of free TH assay kits.
• To explain the physicochemical basis and limitations of widely used free TH assay kits.

Main Methods:

• Evaluation of the theoretical basis and performance of free TH assay kits using diluted samples.
• Analysis of physicochemical concepts underlying analogue-based free TH assay kits.
• Identification of sources of error in analogue-based assays, including analogue conformity and reagent additives.

Main Results:

• The free hormone hypothesis is not universally accepted, necessitating caution when interpreting free TH assay results.
• Analogue-based free TH assays are prone to errors due to non-conforming analogues and interfering reagent additives (e.g., albumin).
• Variability exists between different manufacturers' kits and even between kits from the same manufacturer, leading to differing results.

Conclusions:

• Diagnostic decisions should not solely rely on the assumption of the free hormone hypothesis's validity.
• Assay kit reliability must be judged by analytical criteria, not just performance claims in specific patient categories.
• While some kits may be useful in defined situations, complete reliance is not advised in complex cases like non-thyroidal illness (NTI) due to potential diagnostic misdirection.