Comparison of pituitary and recombinant human thyroid-stimulating hormone (rhTSH) in a multicenter collaborative study: Establishment of the First World Health Organization Reference Reagent for rhTSH

Background: The increasing use of recombinant-DNA-derived materials in ther apy and diagnosis poses a new challenge for biological standardization, tha t of developing reference preparations appropriate for both the native and recombinant products. Here we report the results of an international collab orative study that was carried out under the auspices of WHO to assess the suitability of a preparation of recombinant thyroid-stimulating hormone (rT SH; 94/674) to serve as a potential standard for the calibration of diagnos tic immunoassays compared with the International Reference Preparation (IRP ) for human TSH (80/558). Methods: Coded samples were provided to the 33 laboratories in the study, a nd participants were asked to perform TSH assays currently in use in their laboratories. Twenty-eight laboratories contributed 93 immunoassays in 41 d ifferent method-laboratory combinations, and an additional 5 laboratories c ontributed bioassay data. All data were analyzed centrally at the National Institute for Biological Standards and Control. Results: The results obtained in different laboratories and with different assay systems revealed significant variability between estimates of rTSH re lative to the IRP. These ranged from 5.51 mIU (95% limits, 3.95-7.67 mIU) p er ampoule by RIA to 7.15 mIU (95% limits, 6.7-7.63 mIU) per ampoule by imm unofluorometric assay. However, the results showed that the assignment of a value of 6.70 mIU per ampoule of 94/674 would give reasonable continuity w ith the IRP in many assay systems. Conclusions: The preparation was established as the First WHO Reference Rea gent for TSH, human, recombinant, to provide a means of validating assay pe rformance and to maintain continuity with the IRP without compromising clin ical data. (C) 1999 American Association for Clinical Chemistry.