title: Gaps in the traceability chain of human growth hormone measurements.
abstract: BACKGROUND
  Human growth hormone (hGH) is measured for the diagnosis of secretion disorders. These measurements fall under the EU Directive 98/79/EC on in vitro diagnostic medical devices requiring traceability of commercial calibrator values to higher-order reference materials or procedures (Off J Eur Communities 1998 Dec 7;L 331:1-37). External quality assessment schemes show large discrepancies between results from different methods, even though most methods provide results traceable to the recommended International Standard (IS 98/574). The aim of this study was to investigate possible causes for these discrepancies.
  
  
  METHODS
  We investigated the commutability and recovery of hGH in reconstituted IS 98/574. We tested different reconstitution protocols and used 4 different serum matrices for spiking. These IS preparations were measured together with serum samples. We quantified hGH by 5 different methods in 4 different laboratories.
  
  
  RESULTS
  Results from the different methods correlated well for the serum samples. Mean discrepancies between results from different methods were ≤20%. None of the IS preparations was commutable for all the method comparisons. The recovery of hGH in preparations of IS 98/574 depended on the reconstitution protocol (>10-fold differences) and background matrix (relative differences ≤17% for different serum matrices).
  
  
  CONCLUSIONS
  The use of different protocols for reconstitution and spiking of hGH reference preparations affects quantification by immunoassays, potentially leading to a bias between commercial methods, despite the use of calibrators with values claimed to be traceable to the same higher-order reference material.
authors.affiliation: Institute for Reference Materials and Measurements (IRMM), Joint Research Centre, European Commission, Geel, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Boulo
authors.forename: Katja
authors.initials: K
authors.lastname: Hanisch
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: Cristian-Gabriel
authors.initials: CG
authors.lastname: Arsene
authors.forename: Mauro
authors.initials: M
authors.lastname: Panteghini
authors.forename: Guy
authors.initials: G
authors.lastname: Auclair
authors.forename: Catharine
authors.initials: C
authors.lastname: Sturgeon
authors.forename: Heinz
authors.initials: H
authors.lastname: Schimmel
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zegers
mesh_terms: D002352:Carrier Proteins / Q000097:blood; D002853:Chromatography, Liquid; D019382:Human Growth Hormone / Q000097:blood* / Q000592:standards; D006801:Humans; D007118:Immunoassay / Q000379:methods; D013058:Mass Spectrometry; D012015:Reference Standards
chemical_list: D002352:Carrier Proteins; D019382:Human Growth Hormone; C051815:somatotropin-binding protein