TSH Reference Interval Studyin Japan
Dr. Akira Hishinuma
Dokkyo Medical University, Mibu, Tochigi, Japan

Background• IFCC C-STFT (International Federation of Clinical Chemistry and Laboratory Medicine
Standardization of Thyroid Function Tests) performed TSH harmonization study (phase IV, Clin
Chem 2017;63:1248-60), which enabled 13 IVD manufacturers to report harmonized TSH valuesto clinicians.
• Japan Thyroid Association, Japan Society of Clinical Chemistry, Japanese Society of Laboratory
Medicine, and Japanese Committee for Clinical Laboratory Standards, represented by Akira
Hishinuma, approached Ministry of Health, Labour and Welfare of Japanese government (MHLW)
to have TSH measurements harmonized.
• MHLW contacted Japan Association of Clinical Reagents Industries (JACRI).
• JACRI (all IVD companies) agreed to harmonize TSH.
• Committee of Standardization of Japanese Society of Laboratory Medicine planned andconducted the study with 10 IVD manufactures who have sales permission by MHLW.

Study Population• 120 healthy individuals• Ages 20-60, Average BMI 21• No thyroid illness or serious disease (i.e. hepatic, renal, diabetes, endocrine, and others) is diagnosed to avoid nonthyroid illness.
• No medication which affects thyroid function• No radiological examination with contrast medium containing iodide or radiation therapy in the neck• No OCT drugs for weight loss (Chinese drugs may contain thyroid hormone itself)• Not pregnant or lactating• Living in Japan• Normal values for total protein, AST, ALT, γ-GTP, Cre, Glucose, Na, K, Cl, Triglyceride, Total cholesterol, HBsAg, HCV Ab,HIV, TPO Ab, Tg Ab

ABC
DEFGHIJMEAN
-0.34
-4.34
-5.15
-1.25
2.24
2.10
7.29
3.13
-0.18-3.51

SD
4.21
3.37
6.47
9.27
2.83
2.74
3.61
4.16
6.96
5.51

Distribution of reported results by manufacturer
The mean average differences of the IVD manufacturers from APTM10 were from -5.15% to 7.29%,
whereas the highest SD of the IVD manufacturers was 9.27%.
Therefore, we judged that the phase IV study of C-STFT is assured
and the re-calibrated values will be used without further adjustment in Japan.

According to the above study, each IVD manufacturer is requested to report theIFCC C-STFT (phase IV) value by the end of March, 2021.
To obtain the phase IV values, the following coefficients should be multiplied tothe current kit values which were listed in the phase IV study.
(The order of manufacturers is different from A～J of the previous slide.)
Marketing Authorization Holder in Japan
Abbott Japan Co.,Ltd.
LSI Medience Corporation
Ortho-Clinical Diagnostics
FUJIFILM Wako Pure ChemicalCorporation
Siemens Healthcare Diagnostics K.K.
Sysmex Corporation
Tosoh Corporation

ST AIA-PACK TSH

FUJIREBIO Inc.

Lumipulse® G TSH
Access HYPERsensitive hTSH（Cat. No. 33820
Access2 Immunoassay System）
Elecsys TSH （material number : 08429324190
cobas e 601 module）

Beckman Coulter Inc.
Roche Diagnostics K.K.

Assay NameARCHITECT TSH
STACIA CLEIA TSH
VITROS® TSH New

Instruments/platforms
ARCHITECT i2000SR System
STACIA®
VITROS® 5600

coefficient
to be released
1.30
new kit is planned

Accuraseed TSH

Accuraseed®

1.09

TSH3-Ultra
HISCLTSH Assay Kit

ADVIA Centaur XP
Automated Immunoassay System HISCL®-5000
AUTOMATED IMMUNOASSAY ANALYZER AIA2000
Lumipulse® G1200

1.00
1.07
0.92
to be released
to be released
0.98

The reference interval (RI) of Japanese adults (20～60 years of age)
calculated by APTM10 is 0.61～4.23 mIU/L.