© Schattauer 2015 Nuklearmedizin 1/2015 1 Keywords TSH, reference range, thyroid hormones Summary Setting the reference range for thyrotropin (TSH) remains a matter of ongoing controver- sy. Patients, methods: We used an indirect method to determine the TSH reference range post hoc in a large sample. A total of 399 well characterised subjects showing no evidence of thyroid dysfunction were se- lected for definition of the TSH reference li- mits according to the method of Katayev et al.. To this end, the cumulative frequency was plotted against the individual logarithmic TSH values. Reference limits were calculated by extrapolating the middle linear part of the regression line to obtain the cut-offs for the 95% confidence interval. We also examined biological variation in a sample of 65 sub- jects with repeat measurements to establish reference change values (RCVs). Results: Based on these, the reference interval ob- tained by the novel technique was in close agreement with the conventionally estab- lished limits, but differed significantly from earlier recommendations. Discussion: Follow- ing unverified recommendations could result in a portion of patients with subclinical thyroid dysfunctions being missed, an important con- sideration in a setting with a high prevalence of thyroid autonomy. Conclusion: Indirect post hoc verification of reference intervals from a large retrospective sample is a modern ap- proach that gives plausible results. The method seems particularly useful to assess the adequacy and performance of reference limits reported or established by others in a particu- lar setting. The present data should encourage re-evaluation of reference systems on a broader scale. Schlüsselwörter TSH, Referenzbereich, Schilddrüsenhormone Zusammenfassung Die vorliegende Arbeit befasst sich mit dem Referenzbereich des Thyreotropins (TSH). Patienten, Methoden: Mit der indirekten Me- thode von Katayev et al. wurde der Referenz- bereich von TSH post hoc in einer Gruppe von insgesamt 399 gut untersuchten Personen ohne klinisch fassbare Zeichen einer Schild- drüsendysfunktion erhoben. Dafür wurde die kumulierte Häufigkeit gegen die logarith- mierten TSH-Werte aufgetragen. Der mittlere, lineare Bereich, der dem 95%-Konfidenz- intervall der Regressionsgerade entsprach, war der Referenzbereich. Zudem wurde die biologische Variabilität der Referenzwerte in einer Gruppe von 65 Personen mit Mehrfach- messungen bestimmt. Ergebnisse: Der so be- stimmte Referenzbereich stimmte gut mit ak- tuellen, konventionell erhobenen Referenz- daten überein. Allerdings ergaben sich signi- fikante Unterschiede zu früheren Empfehlun- gen. Diskussion, Schlussfolgerung: Die indi- rekte Post-hoc-Bestimmung des TSH-Refe- renzbereichs aus einer retrospektiven Stich- probe ist ein moderner Ansatz, der plausible Ergebnisse liefert. Die Methode erscheint gut geeignet, um vorgegebene Referenzwerte zu verifizieren. Die vorliegenden Daten sollten Kliniker motivieren, auf diese Weise ihre eige- nen Referenzbereiche festzulegen. Original article Reference range for thyrotropin Post hoc assessment R. Larisch 1 ; A. Giacobino 1 ; W. Eckl 1 ; H.-G. Wahl 2 ; J. E. M. Midgley 3 ; R. Hoermann 1 1 Klinik für Nuklearmedizin, Klinikum Lüdenscheid, Germany; 2 Institut für Laboratoriumsmedizin, Klinikum Lüdenscheid, Germany; 3 North Lakes Clinical, Ilkley, UK Correspondence to: Prof. Dr. Rolf Larisch Department of Nuclear Medicine, Klinikum Luedenscheid, Paulmannshoeher Str 14 58515 Luedenscheid, Germany E-mail: rolf.larisch@klinikum-luedenscheid.de Thyrotropin-Referenzbereich Post-hoc-Festsetzung Nuklearmedizin 2015;54:- http://dx.doi.org/10.3413/Nukmed-0671-14-06 received: June 6, 2014 accepted in revised form: December 17, 2014 epub ahead of print: January 8, 2015 Modern thyroid laboratory evaluation of thyroid function relies heavily on the pitu- itary hormone thyrotropin (TSH), and the more subtle thyroid dysfunctions termed subclinical hypothyroidism or hyperthy- roidism are exclusively based on TSH measurement (3). With the advent of third generation assays techniques have reached a high standard of assay sensitivity and me- thodological reliability. However, a still unresolved controversy has surrounded the determination of the refer- ence range of TSH, particularly its upper limit (4, 5, 13, 19, 22, 27). A lack of standardisation and harmon- isation among the various commercially available methods has added to the contro- versy (24, 25). This makes it mandatory for each institution to establish its own refer- ence ranges. The American Clinical and Laboratory Standards Institute has pub- lished guidelines how to proceed with the For personal or educational use only. No other uses without permission. All rights reserved. Note: Uncorrected proof, epub ahead of print online Downloaded from www.nuklearmedizin-online.de on 2015-01-14 | User: linde.degrande@ugent.be | IP: 157.193.187.242