title: Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods.
abstract: OBJECTIVE
  Patients with non-thyroidal illness syndrome have many abnormalities in thyroid hormone tests. Such patients have medical comorbidities associated with low serum proteins and are on multiple medications that interfere with thyroid hormone measurement by immunoassay platforms. It is unknown if these thyroid hormone measurements reflect physiologic conditions or if they are artifacts of testing methodology.
  
  
  METHODS
  Fifty patients were selected from the intensive care unit (ICU) from our institution. Total and free thyroid hormones in plasma were measured by gold standard liquid chromatography-tandem mass spectrometry (LC-MSMS). The results were compared to the Roche Cobas 6000. Patient medical comorbidities and binding protein levels were assessed.
  
  
  RESULTS
  Concentrations of total 3,5,5'-triidothyronine (TT3) and total thyroxine (TT4) were significantly more likely to be low by LC-MSMS compared to immunoassay. Free 3,5,5'-triidothyronine (FT3) levels were similar by immunoassay and LC-MSMS. However, FT4 concentrations were mildly elevated for many patients when measured by ultrafiltration LC-MSMS (19/50, 38%) compared to 1/50 (2%) when measured by immunoassay (p=0.0001). Decreased albumin and thyroxine binding globulin were common and patients were on an average of 11.7±5.0 medications, all factors known to interfere with results found on immunoassays.
  
  
  CONCLUSIONS
  Marked discrepancies in thyroid hormone measurement were noted between reference LC-MSMS and a common immunoassay platform. It is hypothesized that T4 binding to low affinity albumin is displaced by several drugs, raising concentrations of FT4 by LC-MSMS compared to immunoassay, and that the immunoassay values are falsely decreased due to low binding proteins in our patient population.
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Welsh
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Stolze
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States.
authors.forename: Trisha R
authors.initials: TR
authors.lastname: Podsiadlo
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States. Electronic address: steven.soldin@nih.gov.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Soldin
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D007118:Immunoassay; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013959:Thyroid Diseases / Q000097:blood / Q000175:diagnosis*; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014284:Triiodothyronine; D013974:Thyroxine
keywords: Free thyroid hormone; Immunoassay; LC-MSMS; Total thyroid hormone