Abstract
In the euthyroid person, absolute free thyroxine concentrations remain constant and correlate with the tissue hormone level, its biologic effect and the metabolic status of the patient. However, most circulating thyroid hormone is bound to plasma proteins and only a minute amount is in the unbound free form. Studies have shown that current free thyroxine immunoassays are binding protein dependent. Novel high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS) methods have successfully dealt with problems inherent in many immunoassays for thyroid hormones and afforded improved specificity and accuracy in thyroid hormone measurements. We emphasize problems with thyroid hormone testing employing immunoassays including direct and indirect thyroid hormone immunoassays, sample processing, methods of free hormone separation and review the emerging role of liquid chromatography-tandem mass spectrometry in thyroid hormone testing. The latest generation of tandem mass spectrometers has superior limits of quantification, permitting omission of previously employed derivatization steps. Liquid chromatography-tandem mass spectrometry affords the specificity, precision, and limits of quantification necessary for the reliable measurement of thyroid hormones, enhancing diagnostic capabilities, and affording the profiles of the iodothyronines and thyronamines. These methods are especially important in states of disease and during pregnancy when protein binding is a factor that interferes with other methods for thyroid hormone analysis.