Royal Prince Alfred Hospital

and University of Sydney

Harmonisation of TFTs
Harmonisation Workshop
May 2015

Paul Williams Harmonisation May 2015

 Talk Outline
IFCC initiatives C-STFT (Committee for
standardisation of thyroid function tests).
TSH Examples of assays differences
TSH Reference interval changes
FT4 assay differences and problems
Ranges in Pregnancy . Any Consensus ?
Paul Williams Harmonisation May 2015 From Beastall, G. C_STFT report
UK consensus meeting on thyroid reference intervals (RIs) March 2013
Paul Williams Harmonisation May 2015 From Beastall, G. C_STFT report
UK consensus meeting on thyroid reference intervals (RIs) March 2013
From Thienpont report to C-SFT and FDA (APTM AA procedures Trimmed mean)
From Graham Beastall IFCC report
TSH Assays in Australia

Examples
 TSH Comparison RPAH Immulite Vs Roche non pregnant samples

TSH y = 0.8935x + 0.0244

R = 0.9563

6
Immulite 2000

0
0 2 4 6 8 10

Roche Modular
 Fresh Data from Hobart Immulite vs
Roche TSH (last week)
45
40
y = 1.1882x - 0.4003
35 R = 0.9975
30
25
Cobas

20
15
10
5 Series1
0 Linear (Series1)
-5 0 10 20 30 40
Immulite

6
y = 0.9251x + 0.2117
5 R = 0.9688

4 Series1
Linear (Series1)
Cobas

3
Linear (Series1)
2

1
Data provided by Parameswaran,
0
0 2 Immulite 4 6
Venkateswaran in Hobart
 TSH
6

5
Roche y = 1.1602x + 0.0921
TSH R = 0.9302
4

3
TSH
2 Linear (TSH)

0
0 1 2 3 4 5 6

Immulite TSH

Data From RPAH Immulite Vs Roche TSH Matched for FT4 Pregnant samples
Ann Clin Biochem 2007; 44: 203208
Roche Single step assay
Some Background on TSH assays

With Thanks for the work of Carol

Spencer
Data Provided by Prof. K Sikaris
Harmonised TSH looks to be very
promising for TSH Assays
Can we implement an All procedures
trimmed mean recalibration and
harmonise the Reference intervals ?
 What About FT4 and FT3 ?

Do we wait for standardisation to be

complete and assays to be recalibrated ?
This could be slow because of reluctance to
re-register assays by the Manufacturers.
All assays will increase 30-50% what will be
the clinicians reaction ?
Roche Single step assay
15th IFCC-Conference Clinical Chemistry and Laboratory Medicine Barcelona Spain 2003
Just using assay specific Reference ranges, would we diagnose
the same patients ?
 Multiple line comparison between Values
Thienpont Roche and Abbott
110

100 THP_M
Roche
90 Abbott
80
FT4
70
pmol/L
60

50

40

30

20
0 2 4 6 8 10 12
Data Provided by Prof. K Sikaris
 Recent Data from Hobart Immulite vs
45
Roche FT4 4
+1.96 SD

40 3.3

y = 1.1882x - 0.4003 2

35 R = 0.9975
30

Immulite FT4 - Cobas FT4

0
Mean
-0.8
25 -2
Cobas

20 Series1
-4

15 Linear (Series1) -1.96 SD

-4.8

10 -6

5 -8
10 15 20 25 30 35 40
0 Mean of Immulite FT4 and Cobas FT4

-5 0 10 20 30 40
Immulite

25
Low Free T4
4

y = 1.3533x - 5.4021 3 +1.96 SD

20 R = 0.8311 2.8

Immulite_FT4 1 - Cobas_FT4 1
1
15
Cobas

Mean
0
-0.1
Series1
10 -1

Linear (Series1) -2

5 -3
-1.96 SD
-2.9

-4

0 10 12 14 16 18
Mean of Immulite_FT4 1 and Cobas_FT4 1
20 22

0 5 10 15 20
Immulite
Data provided by Parameswaran, Venkateswaran
 70%

60%
Percentage Elevated fT4

50%
Centaur>20
40%
E170>21
DXL>21
30%
Architect>19
20%

10%

0%
to 0.03 to 0.3 to 5.0 to 50
to 0.1 to 1.0 to 10 >50
TSH

Data Provided by Prof. K Sikaris

Thank You for your attention.

Are we able to start the

discussion ?
 FT4 Manufacturers Reference Range TSH Manufacturers Reference Ranges
30 6
25 5

TSH mIU/L
20 4
FT4 pmol/L

15 3
10 2
5 1
0 0
A SC SD SV SI RC V B A SC SD SV SI RC V B
FT4 Low 9 11.5 9.8 9.8 10.3 12 10 7.9 TSH Low 0.35 0.55 0.36 0.36 0.4 0.27 0.46 0.34
FT4 Mid 14 17.1 14.3 14 14.3 17 14.1 11.1 TSH MID 2.7 2.7 2 2 2.2 2.2 2.6 3
FT4 High 19 22.7 18.8 18.8 24.5 22 28.2 14.4 TSH High 4.9 4.8 3.7 3.7 4 4.2 4.7 5.6

FT3 Manufacturers Reference Ranges

9
8
7
FT3 pmol/L

6
5
4
3
2
1
0
A SC SD SV SI RC V B
FT3 Low 2.6 3.5 3.4 3.3 2.8 3.1 4.3 3.8
FT3 mid 4.2 5 4.8 4.37 4.7 5 6.2 4.9
FT3 high 5.7 6.5 6.1 6.1 6.5 6.8 8.1 6
Data Provided by Prof. K Sikaris
 Manufacturer Defined RI (MD-RI)
Pregnancy Paediatric
Abbott No No
Siemens Advia Centaur No Yes
Siemens Dimensions EXL No Yes
Siemens Vista No Yes
Siemens Immulite Trimester TSH and FT4 Yes detailed
Roche Cobas Elecsys Trimester FT4 Yes
Vitros Trimester FT4 and FT3 No
Beckman Access Trimester FT4 No

4/8 5/8
 Differences between FT4
immunoassays

FT4 ASSAY
Abbott 2-step
Siemens Advia Centaur High MW analogue ?
Siemens Dimensions High MW analogue ?
Siemens Vista
Siemens Immulite High MW analogue ?
Roche Cobas Elecsys 1-step
Vitros Competitive IMA
Beckman Access ??
From Thienpont report to C-SFT and FDA
Table 1. Comparison of TSHs from pregnant women without thyroid disease
* Mann-Whitney-Wilcoxon Test
Table 2. Comparison of TSHs from 112 real world samples
* Mann-Whitney-Wilcoxon Test

TSH (mIU/L) DPC Immulite Roche E-170 Comparison *

N=70 results 2000
Median 1.22 1.51 P<0.001
(IQR) (0.73) (0.84)
2.5th to 97.5th 0.008-4.8 0.03-5.64
centile

Table 2. Comparison of TSHs from 112 real world samples

* Mann-Whitney-Wilcoxon Test

TSH (mIU/L) DPC Immulite 2000 Roche E-170 Comparison *

N=112 results

Median 1.22 1.39 P<0.001

(IQR) (1.66) (2.02)
2.5th to 97.5th 0.004-60 0.005-64.5
centile
Data Provided by Prof. K Sikaris
Data Provided by Prof. K Sikaris
 TSH Methods
E170/ e 601/e 602 (cobas 6000- IA) 74
Roche Diagnostics Elecsys 2010/cobas e411 6
Roche Diagnostics Hitachi cobas c501/c502 2
Abbott ARCHITECT (i1000,i2000,i4000) 70
Abbott ARCHITECT c8000 1
Abbott ARCHITECT i1000SR 7
Abbott AxSYM / AxSYM+ 1
Dimension Vista 4
VITROS ECi /ECi Q 8
VITROS 3600/5600(i ) 17
VITROS 5,1 F S/5600 (c) 1
ADVIA Centaur/ADVIA Centaur XP 52
ADVIA Centaur CP 4
Beckman Coulter Access/Access 2
Beckman Coulter UniCel DxI 600/800 27
Immulite/Immulite 1000 1
Immulite 2000/2000 XPi 1
 Free T4
Roche Diagnostics Elecsys 2010/cobas e411 6
Roche Diagnostics Hitachi cobas c501/c502 2
E170/ e 601/e 602 (cobas 6000- IA) 71
Immulite 2000/2000 XPi 1
Dimension Vista 1
ADVIA Centaur/ADVIA Centaur XP 53
ADVIA Centaur CP 4
Beckman Coulter UniCel DxI 600/800 26
Beckman Coulter Access/Access 2
VITROS ECi /ECi Q 5
VITROS 5,1 F S/5600 (c) 1
VITROS 3600/5600(i ) 13
Abbott ARCHITECT c8000 1
Abbott ARCHITECT i1000SR 6
Abbott ARCHITECT (i1000,i2000,i4000) 67
Abbott AxSYM / AxSYM+ 1
A-Abbott, SC Siemens Centaur, SD Siemens Dimension, SI Siemens
Immulite, RC Roche Cobas, V Vitros, B Beckman Coulter.
A-Abbott, SC Siemens Centaur, SD Siemens Dimension, SI Siemens
Immulite, RC Roche Cobas, V Vitros, B Beckman Coulter.