Inverse log-linear relationship between thyroid-stimulating hormone and free thyroxine measured by direct analog immunoassay and tandem mass spectrometry

Hendrick E. Van Deventer, Damodara R. Mendu, Alan T. Remaley, Steven J. Soldin

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

BACKGROUND: Accurate measurement of free thyroxine (FT4) is important for diagnosing and managing thyroid disorders. Most laboratories measure FT4 by direct analogue immunoassay methods. The validity of these methods have recently been questioned. The inverse log-linear relationship between FT4 and thyroidstimulating hormone (TSH) is well described and provides a physiological rationale on which to base an evaluation of FT 4 assays. METHODS: The study included 109 participants for whom FT4 measurement was requested by their clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH and albumin results. FT4 and TSH were measured by use of the Siemens Immulite immunoassay (IA). FT4 was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/ MS) (MS-FT4). RESULTS: The inverse log-linear correlation coefficient between TSH and FT4 was significantly better (P<0.0001) for MS-FT4 (0.84, 95% CI, 0.77- 0.88) than for IA-FT4 (0.45, 95% CI, 0.29-0.59). IA-FT4 showed a significant correlation with albumin (Spearman correlation coefficient 0.45, 95% CI, 0.29-0.5, P<0.0001) and thyroxine-binding globulin (TBG) (Spearman correlation coefficient 0.23, 95% CI, 0.05- 0.41, P<0.02). In contrast, FT4 measurement by LC-MS/MS did not show a significant correlation with albumin or TBG. CONCLUSIONS: The inverse log-linear relationship between FT4 and TSH was significantly better for FT4 measured by LC-MS/MS than by IA. The MS-FT4method therefore provides FT 4 results that agree clinically with those obtained for TSH. Additionally, the significant correlation between IA-FT4 with albumin and TBG suggests that this FT4 method depends on binding protein concentrations and consequently does not accurately reflect FT4.

Original languageEnglish (US)
Pages (from-to)122-127
Number of pages6
JournalClinical Chemistry
Volume57
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

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Direct analogs
Thyrotropin
Tandem Mass Spectrometry
Thyroxine
Immunoassay
Mass spectrometry
Thyroxine-Binding Globulin
Hormones
Albumins
Liquid chromatography
Liquid Chromatography
Assays
Carrier Proteins
Thyroid Gland

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Inverse log-linear relationship between thyroid-stimulating hormone and free thyroxine measured by direct analog immunoassay and tandem mass spectrometry. / Van Deventer, Hendrick E.; Mendu, Damodara R.; Remaley, Alan T.; Soldin, Steven J.

In: Clinical Chemistry, Vol. 57, No. 1, 01.2011, p. 122-127.

Research output: Contribution to journalArticle

Van Deventer, Hendrick E. ; Mendu, Damodara R. ; Remaley, Alan T. ; Soldin, Steven J. / Inverse log-linear relationship between thyroid-stimulating hormone and free thyroxine measured by direct analog immunoassay and tandem mass spectrometry. In: Clinical Chemistry. 2011 ; Vol. 57, No. 1. pp. 122-127.
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abstract = "BACKGROUND: Accurate measurement of free thyroxine (FT4) is important for diagnosing and managing thyroid disorders. Most laboratories measure FT4 by direct analogue immunoassay methods. The validity of these methods have recently been questioned. The inverse log-linear relationship between FT4 and thyroidstimulating hormone (TSH) is well described and provides a physiological rationale on which to base an evaluation of FT 4 assays. METHODS: The study included 109 participants for whom FT4 measurement was requested by their clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH and albumin results. FT4 and TSH were measured by use of the Siemens Immulite immunoassay (IA). FT4 was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/ MS) (MS-FT4). RESULTS: The inverse log-linear correlation coefficient between TSH and FT4 was significantly better (P<0.0001) for MS-FT4 (0.84, 95{\%} CI, 0.77- 0.88) than for IA-FT4 (0.45, 95{\%} CI, 0.29-0.59). IA-FT4 showed a significant correlation with albumin (Spearman correlation coefficient 0.45, 95{\%} CI, 0.29-0.5, P<0.0001) and thyroxine-binding globulin (TBG) (Spearman correlation coefficient 0.23, 95{\%} CI, 0.05- 0.41, P<0.02). In contrast, FT4 measurement by LC-MS/MS did not show a significant correlation with albumin or TBG. CONCLUSIONS: The inverse log-linear relationship between FT4 and TSH was significantly better for FT4 measured by LC-MS/MS than by IA. The MS-FT4method therefore provides FT 4 results that agree clinically with those obtained for TSH. Additionally, the significant correlation between IA-FT4 with albumin and TBG suggests that this FT4 method depends on binding protein concentrations and consequently does not accurately reflect FT4.",
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AU - Soldin, Steven J.

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AB - BACKGROUND: Accurate measurement of free thyroxine (FT4) is important for diagnosing and managing thyroid disorders. Most laboratories measure FT4 by direct analogue immunoassay methods. The validity of these methods have recently been questioned. The inverse log-linear relationship between FT4 and thyroidstimulating hormone (TSH) is well described and provides a physiological rationale on which to base an evaluation of FT 4 assays. METHODS: The study included 109 participants for whom FT4 measurement was requested by their clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH and albumin results. FT4 and TSH were measured by use of the Siemens Immulite immunoassay (IA). FT4 was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/ MS) (MS-FT4). RESULTS: The inverse log-linear correlation coefficient between TSH and FT4 was significantly better (P<0.0001) for MS-FT4 (0.84, 95% CI, 0.77- 0.88) than for IA-FT4 (0.45, 95% CI, 0.29-0.59). IA-FT4 showed a significant correlation with albumin (Spearman correlation coefficient 0.45, 95% CI, 0.29-0.5, P<0.0001) and thyroxine-binding globulin (TBG) (Spearman correlation coefficient 0.23, 95% CI, 0.05- 0.41, P<0.02). In contrast, FT4 measurement by LC-MS/MS did not show a significant correlation with albumin or TBG. CONCLUSIONS: The inverse log-linear relationship between FT4 and TSH was significantly better for FT4 measured by LC-MS/MS than by IA. The MS-FT4method therefore provides FT 4 results that agree clinically with those obtained for TSH. Additionally, the significant correlation between IA-FT4 with albumin and TBG suggests that this FT4 method depends on binding protein concentrations and consequently does not accurately reflect FT4.

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