A multicenter evaluation of dysthyroxinemia in a defined patient cohort

Mario H.J. Vogt 1 , Judith A.P. Bons 2 , Marcel J.W. Janssen 3 , Andre Naus 1 , Wytze Oosterhuis 4 , Joop ten Kate 5 ,  and Paul P.C.A. Menheere 2
  • 1 Department of Clinical Chemistry and Hematology, Laurentius Hospital, Roermond, The Netherlands
  • 2 Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands
  • 3 Department of Clinical Chemistry and Hematology, Viecuri Medical Center, Venlo, The Netherlands
  • 4 Department of Clinical Chemistry and Hematology, Atrium Medical Center, Heerlen, The Netherlands
  • 5 Department of Clinical Chemistry and Hematology, Orbis Medical Center, Sittard-Geleen, The Netherlands
Mario H.J. Vogt, Judith A.P. Bons, Marcel J.W. Janssen, Andre Naus, Wytze Oosterhuis, Joop ten Kate and Paul P.C.A. Menheere


Background: In the region Limburg (The Netherlands) almost all of the five participating laboratories use a different immunoassay platform to determine thyroid stimulating hormone (TSH) and free thryoxine (FT4). With the frequent transfer of patients within the region, harmonization of test result interpretation is necessary. In this study, we investigated dysthyroxinemia classification between participating laboratories and developed procedures for improvement.

Methods: Two ring surveys with an interval of 2 years were performed. Four patient groups (n=100) with different dysthyroxinemia classification were based on biochemical results of the Autodelphia analyzer. Samples were tested in five participating laboratories. In each group the percentage of patients classified with dysthyroxinemia was calculated and differences were analyzed by the Fisher’s exact test.

Results: After the first survey, the percentage of patients with hyperthyroxinemia was more than 20% lower in three laboratories compared to the other two. Bhattacharya analysis revealed that the upper reference limit of FT4 was 20%–30% too high in two laboratories. Adjustments of reference ranges appeared to be effective in the second survey. The third laboratory reported significantly lower percentages of patients with hyperthyroxinemia in the second survey. New FT4 reference ranges were determined for this laboratory, resulting in adequate classification of hyperthyroxinemia.

Conclusions: This study illustrates the potential of a multicenter evaluation of dysthyroxinemia in a biochemical-defined patient cohort. In particular, classification of hyperthyroxinemia differed between laboratories. Adjustments of reference ranges resulted in better agreement of dysthyroxinemia classification. Even using internal and external quality assurance programs, application of multicenter ring surveys is advised to prevent inadequate reference ranges.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.