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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 57, Issue 2


A multicenter study for the evaluation of the reference interval for TSH in Italy (ELAS TSH Italian Study)

Aldo Clerico
  • Corresponding author
  • Laboratory of Cardiovascular Endocrinology and Cell Biology, Department of Laboratory Medicine, Fondazione CNR-Regione Toscana Gabriele Monasterio, Scuola Superiore Sant’Anna, Via Trieste 41, 56126 Pisa, Italy
  • Email
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/ Tommaso Trenti / Rosalia Aloe
  • Dipartimento di Biochimica ad Elevata Automazione, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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/ Ruggero Dittadi
  • U.O.C. Laboratorio Analisi, Ospedale dell’Angelo, AULSS3 Serenissima, Mestre, Venezia, Italy
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/ Sara Rizzardi
  • Laboratorio Analisi Aziendale (SC), Azienda Socio-Sanitaria Territoriale di Cremona, Istituti Ospitalieri, Cremona, Italy
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/ Marco Migliardi / Roberta Musa
  • Dipartimento di Biochimica ad Elevata Automazione, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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/ Mariella Dipalo
  • Dipartimento di Biochimica ad Elevata Automazione, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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  • De Gruyter OnlineGoogle Scholar
/ Concetta Prontera / Silvia Masotti / Veronica Musetti / Renato Tozzoli
  • Clinical Pathology Laboratory, Department of Laboratory Medicine, Azienda per l’Assistenza Sanitaria n.5, Pordenone Hospital, Pordenone, Italy
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/ Andrea PadoanORCID iD: https://orcid.org/0000-0003-1284-7885 / Marcello Bagnasco /
Published Online: 2018-07-17 | DOI: https://doi.org/10.1515/cclm-2018-0541



The aims of this study were: (1) to calculate reliable thyroid stimulating hormone (TSH) reference intervals using laboratory databases; (2) to evaluate the relationship between TSH, sex and age values in different large Italian populations.


The TSH values stored in the laboratory information system of clinical laboratories of four Italian city hospitals, including 146,801 TSH measurements (with the respective age and sex data of individuals) were taken in consideration. Assuming a log-normal distribution, to log-transformed TSH values were applied the Dixon’s iterative principle in order to exclude the outliers. At the end of this iterative process 142,821 log-transformed TSH results remained. The four clinical laboratories measured serum TSH concentrations using the same TSH immunoassay method (Access TSH 3rd IS, using UniCel DxI platform).


The TSH reference interval calculated in the present study (0.362–5.280 mIU/L) is similar to that suggested by the manufacturer for the Access TSH 3rd IS assay (0.45–5.33 mIU/L). TSH values in females were significantly higher than in males (females: mean=2.06 mIU/L; standard deviation [SD]=1.26 mIU/L; n=101,243; males: mean=1.92 mIU/L; SD=1.19 mIU/L; n=41,578; p<0.0001). Moreover, a negative linear relationship was observed between TSH throughout all interval age values (from 0 to 105 years).


The results of the present multicenter study confirm that data mining techniques can be used to calculate clinically useful reference intervals for TSH. From a pathophysiological point of view, our results suggest that some Northern populations of Italy might still suffer some harmful effects on the thyroid gland due to mild to moderate iodine intake deficiency. Specific clinical trials are needed to confirm these results.

This article offers supplementary material which is provided at the end of the article.

Keywords: data mining technique; immunoassay methods; population study; reference intervals; thyroid stimulating hormone (TSH)


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About the article

Corresponding author: Prof. Aldo Clerico, MD, Coordinator, Laboratory of Cardiovascular Endocrinology and Cell Biology, Department of Laboratory Medicine, Fondazione CNR-Regione Toscana Gabriele Monasterio, Scuola Superiore Sant’Anna, Via Trieste 41, 56126 Pisa, Italy, Phone: +39 3152133, Fax: +39 3152024

Received: 2018-05-23

Accepted: 2018-06-18

Published Online: 2018-07-17

Published in Print: 2018-12-19

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 2, Pages 259–267, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2018-0541.

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