Reference range for thyrotropin

 

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Summary

Setting the reference range for thyrotropin (TSH) remains a matter of ongoing controversy. 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 selected for definition of the TSH reference limits 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 subjects with repeat measurements to establish reference change values (RCVs). Results: Based on these, the reference interval obtained by the novel technique was in close agreement with the conventionally established limits, but differed significantly from earlier recommendations. Discussion: Following unverified recommendations could result in a portion of patients with subclinical thyroid dysfunctions being missed, an important consideration 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 approach 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 particular setting. The present data should encourage re-evaluation of reference systems on a broader scale.

Zusammenfassung

Die vorliegende Arbeit befasst sich mit dem Referenzbereich des Thyreotropins (TSH). Patienten, Methoden: Mit der indirekten Methode von Katayev et al. wurde der Referenzbereich von TSH post hoc in einer Gruppe von insgesamt 399 gut untersuchten Personen ohne klinisch fassbare Zeichen einer Schilddrüsendysfunktion erhoben. Dafür wurde die kumulierte Häufigkeit gegen die logarithmierten 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 Mehrfachmessungen bestimmt. Ergebnisse: Der so bestimmte Referenzbereich stimmte gut mit aktuellen, konventionell erhobenen Referenzdaten überein. Allerdings ergaben sich signifikante Unterschiede zu früheren Empfehlungen. Diskussion, Schlussfolgerung: Die indirekte Post-hoc-Bestimmung des TSH-Referenzbereichs aus einer retrospektiven Stichprobe 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 eigenen Referenzbereiche festzulegen.

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