Tandem Mass Spectrometry Improves the Accuracy of Free Thyroxine Measurements During Pregnancy

Abstract

Objective-Pregnancy is a time of rapidly changing demands on the thyroid axis, and knowledge of thyroid hormone levels, especially during the first trimester, is important for ensuring maternal and fetal health. The thyroid hormone assays currently in use become more inaccurate at extremes of binding protein concentrations and when heterophilic antibodies are present. Pregnancy is characterized by both these conditions, making accurate determination of free thyroid hormone levels by conventional direct analog immunoassay methods difficult. The objective of this study was to characterize the performance of a novel tandem mass spectrometric assay for free thyroxine during the physiologic conditions of pregnancy.Design-Healthy women without a history of thyroid abnormalities were recruited from the obstetrics and gynecology and endocrinology clinics of a university medical center and their thyroid status was monitored. Free thyroxine levels were assessed by both immunoassay and tandem mass spectrometry during the course of their pregnancy. Serum thyrotropin levels were also measured. The distributions of free thyroid concentrations obtained by the two assays were compared.Main outcome-The tandem mass spectrometry and immunoassay values did not correlate well with each other. However, tandem mass spectrometry values correlated well with the current gold standard equilibrium dialysis values. Moreover, the good agreement between equilibrium dialysis and tandem mass spectrometry was maintained across all weeks of gestation.Conclusions-We conclude that tandem mass spectrometry has a superior performance to immunoassay for the measurement of free thyroxine during pregnancy. Furthermore, it is ideally suited to generating trimester-specific reference intervals for free thyroxine levels. Future studies will determine if it is a better assay to use in most clinical circumstances.

Second-Trimester Reference Intervals for Thyroid Tests: The Role of Ethnicity

“…The use of tandem mass spectrometry may improve the accuracy of FT4 measurements during pregnancy (25 ). This technique is resistant to potential interference from heterophile antibodies, which may affect measurements by immunoassay throughout pregnancy (26,27 ).…”

CONTROVERSIES IN ENDOCRINOLOGY: On the need for universal thyroid screening in pregnant women

“…In contrast, the measurement of maternal FT 4 with the immunoassay techniques currently used presents some difficulties due to insufficient accuracy by virtue of the interference of pregnancy-modified plasma proteins. It has been recently shown that certain FT 4 immunoassays can be quite similar to tandem mass spectrometry, which in turn has proven to have a high correlation with equilibrium dialysis, which is the gold standard for measurement of FT 4 during pregnancy (75,76). The determination of total T 4 (TT 4 ) has also been proposed as an alternative method for evaluating thyroid function during pregnancy, as TT 4 measurements are performed by a more robust methodology than those used for FT 4 .…”

“…Although FT 4 measurement during pregnancy has some technical problems and its concentrations are particularly low in the third trimester compared with the nonpregnant population, the combination of a robust screening parameter such as TSH, as the first line approach, complemented with FT 4 measured with a method showing a good correlation with equilibrium dialysis or tandem mass spectrometry, which could allow a realistic and reliable protocol for detecting TD early in pregnancy. In the near future, tandem mass spectrometry, which has shown a very good correlation with equilibrium dialysis during gestation (76), may be the technique to be used for such purposes. Another factor to consider during pregnancy is the observed inverse relationship between FT 4 and weight (127,128).…”

Changes of Thyroid Function Tests in Pregnancy and Contribution of Trimester Specific Reference Ranges to Diagnosis

“…Measurement of fT4 in the dialysate or ultrafiltrate of serum samples using liquid chromatography/tandem mass spectrometry appears to be the most reliable method and when this is used, fT4 concentrations were shown to decrease gradually with advancing gestational age, particularly between the 1 st and 2 nd trimester. 12,13 This assay is relatively expensive and not universally available. Routine fT4 assays (and probably fT3 assays) frequently fail to meet performance standards in pregnant women, owing to increases in TBG and decreases in albumin concentrations that cause the immunoassay to be unreliable.…”