CAMPUS INNENSTADT MEDIZINISCHE KLINIK UND POLIKLINIK IV
LB-11
ENDOKRINOLOGISCHES LABOR
Inter-laboratory comparison of IGF-I concentrations measured by an automated immunoassay: Results from a multicentre study across Europe Philipp Grimminger 1, Jan Frystyk 2, Oliver Blankenstein3, Berthold P Hauffa4, Gudmundur Johansson5, Anneke C Muller Kobold6, Jürgen Kratzsch7, Etienne Cavalier 8, Alessia Piazza9, Christian Wüster 10, Phillip Monaghan11, Michael Droste12, Yolanda B de Rijke13, Martin Bidlingmaier 1 1 Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany, 2 Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark, 3 Labor Berlin - Charité Vivantes GmbH, Fachbereich Endokrinologie & Stoffwechsel, Berlin, Germany, 4 Abteilung für pädiatrische Endokrinologie und Diabetologie, Zentrum für Kinderheilkunde und Jugendmedizin, Klinik für Kinderheilkunde II – Universität Duisburg-Essen, Essen, Germany, 5 Department of Endocrinology, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 6 Dept. of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands, 7 Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Universitätsklinikum Leipzig, Leipzig, Germany, 8 Department of Clinical Chemistry, University of Liège, CHU de Liège, Liège, Belgium, 9 Immunodiagnostic Systems S.A., Liège , Belgium, 10 Hormon- & Stoffwechselzentrum, MED Facharztzentrum, Mainz, Germany, 11 The Christie Pathology Partnership, The Christie Hospital, Manchester, UK, 12 Praxis für Endokrinologie und Diabetologie – Oldenburg, Oldenburg, Germany, 13 Depts of Internal Medicine and Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands. Contact:
[email protected]
Materials and Methods
Introduction Measurement of Insulin-like Growth-factor I (IGF-I) is key in diagnosis and monitoring of Growth Hormone (GH) related diseases. Considerable variability between results from different assays, but also between different laboratories using the same assay was a major concern in the past. Recently, we reported age- and sexspecific reference intervals for IGF-I measured by a new automated assay (IDS-iSYS)a. We now evaluated the between laboratory agreement of measurements of IGF-I using this assay in laboratories across Europe.
52 samples (serum; normal n=20, GH deficiency/GH excess n=20, QC samples n=12) were aliquoted, distributed to participating laboratories (n=13) and measured using one batchb of the IDS-iSYS IGF-I assay. Results were reported in mass units (ng/mL). SD scores based on the reference intervalsa were calculated by the LMS formula in 7 labs.
58th Symposium of the German Endocrine Society, Lübeck, 18. -21. March 2015
Results IGF-I concentrations from 20 to 650 ng/mL were observed for the patients’ samples (Figure 1), while for the QC samples (Figure 3) the range was from 13 to 1056 ng/mL. Due to the lack of a gold standard for the measurement of IGF-I, results were compared to the mean values of all laboratories (the all participants mean, APM). Passing-Bablok Fits showed that the individual laboratories results (ILR) are very close to the APM: slopes between 0.963 and 1.045 were calculated for the correlation of the patients’ samples and between 0.961 and 1,049 for the correlation of the QC samples. A closer analysis of the differences from each ILR to the APM with Bland Altman plots (Figure 2) confirms this observation: a mean Bias between -3.32% and +4.89% (mean -0.00%) for serum samples and between -7.49% and +4,83% (mean -0.11%) for QC samples. 95% of all results (concentrations) were within +/-8.6% of the APM. Corresponding SD scores ranged from -4.18 to +6.79 and were highly correlated between labs (0.974 to 1.037).
Fig 1. Results of all laboratories: IGF-I of Patients’ samples compared to all participants mean (APM).
Fig 2. Bland Altman plots for the IGF-I results of the patients’ samples in each laboratory. The relative Difference for each sample is compared to the all participants mean (APM). Fig 3. IGF-I results of the QC samples for all laboratories. 2 outliers were excluded (see asterisk).
Fig 4. SD Scores on the IGF-I results of the patients’ samples for 7 participating laboratories.
Discussion and Summary Our data demonstrate very good agreement of IGF-I concentrations measured by the IDS-iSYS assay in laboratories across Europe, especially in real patients’ samples. SD scores calculated by the same mathematical method also exhibit strong agreement between laboratories. Harmonisation of assay reagents and statistical methods to calculate SD scores is key to reduce between laboratory differences in determination and interpretation of IGF-I data. a
Bidlingmaier et al, J Clin Endocrinol Metab. 2014 May;99(5):1712-21
b
Bidlingmaier et al, Lot-to-Lot Stability of the IDS-iSYS IGF-I Immunoassay, Poster at the ENDO 2015
