| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Editorials |
Laboratory for Analytical Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Belgium
Address correspondence to the author at:, Harelbekestraat, 72, Gent, Belgium B-9000, E-mail linda.thienpont{at}ugent.be
In the field of free thyroid hormone testing, methods based on equilibrium dialysis (ED) or ultrafiltration (UF) of serum, before direct measurement of the hormone concentration in the dialysate or ultrafiltrate, are accepted to be gold standards(1). These measurement procedures, however, physically isolate the free from the protein-bound hormone fractions and have been considered too technically demanding, inconvenient, and relatively expensive for routine clinical laboratory use(2)(3). Typically, such methods are better suited for use in reference laboratories(4).
In this issue of Clinical Chemistry, Yue et al. report on the application of an ED isotope dilution–liquid chromatography/tandem mass spectrometric (ID–LC-MS/MS) procedure developed in-house for the routine determination of both serum free thyroxine (FT4) and triiodothyronine (FT3)(5). The procedure makes use of several recent developments: ED devices that allow simultaneous assay of small volumes of 96 samples, on-line sample preparation techniques, and high-end LC-MS/MS instrumentation with sufficient sensitivity for measurement of thyroid hormone concentrations at the picomole per liter level.
This report by Yue et al. marks a major step forward in the analysis of serum free thyroid hormones. The reference technology has now been made available for the routine laboratory, and controversies may now be resolved regarding the validity of free thyroid hormone determinations by some immunoassays [e.g., (6)(7)(8)(9)]. Interestingly, Yue et al. report on method comparison studies with 2 immunoassays that show excellent correlation with the newly developed ED ID–LC-MS/MS procedure but at the same time, reveal standardization problems.
Although the ED ID–LC-MS/MS procedure brings many potential benefits, it also poses some problems. In view of the aforementioned controversy regarding the validity of current methods for measuring free thyroid hormone, interest in the development of in-house ED or UF ID–LC-MS/MS procedures is likely to be extraordinary. Consequently, it is to be expected that many procedures will be developed worldwide, using different separation techniques (UF or ED) under different conditions (e.g., serum prediluted or not, pH buffered at 7.4 or not, assays performed at room temperature or at the recommended 37 °C). To prevent discrepant measurement results caused by such variations, the need for thorough validation of the procedures, preferably by an internationally accepted reference measurement procedure performed in a recognized reference laboratory, cannot be overemphasized(3). Without such confirmatory studies, the validity of ED or UF ID–LC-MS/MS for free thyroid hormone measurement may be compromised by uncontrolled proliferation of assay procedures.
Additionally, laboratory-developed in-house tests that directly compete with commercial tests may necessitate a modified regulatory environment. In the most extreme view, clinical laboratories that develop in-house tests could be regarded as manufacturers of medical devices and therefore would require more stringent evaluation. In that connection, it is worth mentioning that the Working Group on Standardization of Thyroid Function Tests of the IFCC recently proposed an ED ID–LC-MS/MS procedure as candidate international conventional reference measurement procedure for FT4 in serum(10)(11). Currently, this Working Group is preparing for a method comparison study of serum FT4 measurement with the participation of immunoassay manufacturers and laboratories that have developed in-house ED or UF ID–MS assays for FT4.
Acknowledgments
Grant/Funding Support: None declared.
Financial Disclosures: L.M.T. is director of a reference laboratory at Ghent University.
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
