ms_06445896190V3.

Elecsys Tg II
Elecsys 2010
MODULAR ANALYTICS E170
06445896 190 100 cobas e 411
cobas e 601
cobas e 602

English patients and patients with recurrence of disease who need further diagnosis
and treatment. Alternatively, institutional cut‑off levels can be established to
Please note tailor the follow-up strategies to the local patient population and the
Thyroglobulin (Tg) determinations can be affected by the presence of Tg thyroglobulin test used.8,9,10,13
autoantibodies (anti‑Tg) in some patient samples. These autoantibodies All Tg results should be interpreted in conjunction with the total clinical
presentation of the patient, including symptoms, clinical history, data from
may interfere with the assay used to measure Tg, causing false high or additional tests (i.e. neck ultrasound, whole body scan) and other
false low Tg values.1,2 appropriate information.
The measured Tg value of a patient’s sample can also vary depending on Tg determinations can be affected by the presence of Tg autoantibodies
the assay used. The laboratory finding must therefore always contain a causing false high or false low Tg values. Therefore anti‑Tg determinations
statement on the Tg assay method used. Tg values determined on patient are recommended for all Tg samples to rule out this interference.1,2
samples by different assays cannot be directly compared with one Test principle
another and could be the cause of erroneous medical interpretations. If Sandwich principle. Total duration of assay: 18 minutes.
there is a change in the Tg assay procedure used while patient ▪ 1st incubation: Tg from 35 µL of sample, a biotinylated monoclonal
monitoring, the Tg values obtained upon changing to the new procedure Tg‑specific antibody and monoclonal Tg‑specific antibodies labeled with
must be confirmed by parallel measurements with both methods.2,3 a ruthenium complexa) react to form a sandwich complex.
Intended use ▪ 2nd incubation: After addition of streptavidin-coated microparticles, the
complex becomes bound to the solid phase via interaction of biotin and
Immunoassay for the in vitro quantitative determination of thyroglobulin in streptavidin.
human serum and plasma. Determination of Tg is used as an aid in
monitoring after thyroid ablation. ▪ The reaction mixture is aspirated into the measuring cell where the
microparticles are magnetically captured onto the surface of the
The electrochemiluminescence immunoassay “ECLIA” is intended for use electrode. Unbound substances are then removed with
on Elecsys and cobas e immunoassay analyzers. ProCell/ProCell M. Application of a voltage to the electrode then induces
Summary chemiluminescent emission which is measured by a photomultiplier.
Thyroglobulin (Tg) is a glycoprotein with a molecular weight of ▪ Results are determined via a calibration curve which is instrument-
approximately 660 kDa.4 Tg is synthesized in large quantities by the specifically generated by 2‑point calibration and a master curve provided
thyrocytes and released into the lumina of the thyroid follicles. Production of via the reagent barcode.
Tg is stimulated by TSH, intrathyroidal iodine deficiency and the presence a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy) )
of thyroid-stimulating immunoglobulins.
Reagents - working solutions
Tg plays a decisive role in the synthesis of the peripheral thyroid hormones
T3 and T4. It contains about 130 tyrosine residues, some of which can be The reagent rackpack is labeled as TG II.
iodinated to monoiodo- and diiodothyrosine (MIT and DIT) in the presence
of TPO (thyroid peroxidase) and iodide.3 The subsequent coupling of MIT M Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5 mL:
and DIT to form T3 and T4 also takes place on the Tg‑matrix with the Streptavidin-coated microparticles 0.72 mg/mL; preservative.
involvement of TPO.5
R1 Anti‑Tg-Ab~biotin (gray cap), 1 bottle, 9 mL:
During synthesis of Tg by the thyrocytes and the transport of Tg to the
follicles, small quantities of the protein can pass into the bloodstream. Biotinylated monoclonal anti‑Tg antibody (mouse) 1 mg/L; Bis‑Tris
Accordingly, low concentrations of Tg can be found in the blood of healthy buffer 50 mmol/L, pH 6.3; preservative.
individuals not suffering from thyroid diseases.
R2 Anti‑Tg‑Ab~Ru(bpy) (black cap), 1 bottle, 9 mL:
Elevated Tg concentrations have been reported in different thyroid
conditions like Hashimoto’s disease, Graves’ disease, thyroid adenoma, Monoclonal anti‑Tg antibodies (mouse) labeled with ruthenium
and thyroid carcinoma. The determination of Tg can also be helpful to complex 3.1 mg/L; Bis‑Tris buffer 50 mmol/L, pH 6.3; preservative.
distinguish between subacute thyroiditis and factitious thyrotoxicosis. In
cases of congenital hypothyroidism the determination of Tg can be used to Precautions and warnings
differentiate between the complete absence of the thyroid gland and thyroid For in vitro diagnostic use.
hypoplasia or other pathological conditions.5,6,7 Exercise the normal precautions required for handling all laboratory
The main application of Tg testing is the post‑operative follow‑up of patients reagents.
with differentiated thyroid carcinoma (DTC). As the thyroid gland is the only Disposal of all waste material should be in accordance with local guidelines.
known source of Tg, the serum Tg level will drop to a very low or Safety data sheet available for professional user on request.
undetectable concentration after total or near‑total thyroidectomy and Avoid foam formation in all reagents and sample types (specimens,
successful radioiodine ablation of the residual thyroid tissue. In patients calibrators and controls).
who have undergone a partial thyroidectomy Tg levels will still be
measurable depending on how much tissue is remaining after surgery. Reagent handling
Detectable levels of serum Tg after total thyroidectomy are indicative of The reagents in the kit have been assembled into a ready‑for‑use unit that
persistent or recurrent DTC. In consequence significantly increasing Tg cannot be separated.
levels are interpreted as a sign of recurrence of the disease.8,9,10,11,12,13
All information required for correct operation is read in from the respective
Using very sensitive Tg assays an increased number of reagent barcodes.
‘thyroglobulin‑positive’ patients may be observed, even if patients show no
clinical evidence of disease.13 These patients cannot be defined as Storage and stability
disease‑free and should be monitored according to current guidelines. Store at 2‑8 °C.
Different cut‑off values are published to distinguish between monitoring Do not freeze.
2017-09, V 3.0 English 1/4
ms_06445896190V3.0

Elecsys Tg II
Store the Elecsys reagent kit upright in order to ensure complete ▪ 12102137001, AssayTip/AssayCup Combimagazine M,
availability of the microparticles during automatic mixing prior to use. 48 magazines x 84 reaction vessels or pipette tips, waste bags
Stability: ▪ 03023150001, WasteLiner, waste bags
▪ 03027651001, SysClean Adapter M
unopened at 2‑8 °C up to the stated expiration date
Accessories for all analyzers:
after opening at 2‑8 °C 84 days (12 weeks)
▪ 11298500316, Elecsys SysClean, 5 x 100 mL system cleaning
on the analyzers 28 days (4 weeks) solution
Specimen collection and preparation Assay
Only the specimens listed below were tested and found acceptable. For optimum performance of the assay follow the directions given in this
document for the analyzer concerned. Refer to the appropriate operator’s
Serum collected using standard sampling tubes or tubes containing manual for analyzer‑specific assay instructions.
separating gel.
Resuspension of the microparticles takes place automatically prior to use.
Li‑heparin, K2‑ and K3‑EDTA plasma. Read in the test‑specific parameters via the reagent barcode. If in
Stable for 48 hours at 15‑25 °C, 72 hours at 2‑8 °C, 1 month at ‑20 °C.14 exceptional cases the barcode cannot be read, enter the 15‑digit sequence
Freeze only once. of numbers.
The sample types listed were tested with a selection of sample collection MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers:
tubes that were commercially available at the time of testing, i.e. not all PreClean M solution is necessary.
available tubes of all manufacturers were tested. Sample collection systems Bring the cooled reagents to approximately 20 °C and place on the reagent
from various manufacturers may contain differing materials which could disk (20 °C) of the analyzer. Avoid foam formation. The system
affect the test results in some cases. When processing samples in primary automatically regulates the temperature of the reagents and the
tubes (sample collection systems), follow the instructions of the tube opening/closing of the bottles.
manufacturer.
Centrifuge samples containing precipitates before performing the assay. Calibration
Traceability: This method has been standardized against CRM (Certified
Do not use heat‑inactivated samples. Reference Material) 457, of the BCR (Community Bureau of Reference) of
Do not use samples and controls stabilized with azide. the European Union.15
Ensure the samples, calibrators and controls are at 20‑25 °C prior to Every Elecsys reagent set has a barcoded label containing specific
measurement. information for calibration of the particular reagent lot. The predefined
Due to possible evaporation effects, samples, calibrators and controls on master curve is adapted to the analyzer using the relevant CalSet.
the analyzers should be analyzed/measured within 2 hours. Calibration frequency: Calibration must be performed once per reagent lot
Materials provided using fresh reagent (i.e. not more than 24 hours since the reagent kit was
registered on the analyzer). Renewed calibration is recommended as
See “Reagents – working solutions” section for reagents. follows:
Materials required (but not provided) ▪ after 1 month (28 days) when using the same reagent lot
▪ 06445900190, Tg II CalSet, for 4 x 1 mL ▪ after 7 days (when using the same reagent kit on the analyzer)
▪ 11731416190, PreciControl Universal, for 2 x 3 mL each of ▪ as required: e.g. quality control findings outside the defined limits
PreciControl Universal 1 and 2 or
06445918190, PreciControl Thyro Sensitive, for 4 x 2 mL Quality control
▪ 03609987190, Diluent MultiAssay, 2 x 16 mL sample diluent For quality control, use PreciControl Universal or PreciControl Thyro
Sensitive.
▪ Anti‑Tg assay, to verify the presence of antibodies to Tg in patient In addition, other suitable control material can be used.
samples (e.g. Anti‑Tg assay, 04738578191)
Controls for the various concentration ranges should be run individually at
▪ 06513107190, Tg II Confirmatory Test least once every 24 hours when the test is in use, once per reagent kit, and
▪ Distilled or deionized water following each calibration.
▪ General laboratory equipment The control intervals and limits should be adapted to each laboratory’s
individual requirements. Values obtained should fall within the defined
▪ Elecsys 2010, MODULAR ANALYTICS E170 or cobas e analyzer limits. Each laboratory should establish corrective measures to be taken if
Accessories for Elecsys 2010 and cobas e 411 analyzers: values fall outside the defined limits.
▪ 11662988122, ProCell, 6 x 380 mL system buffer Follow the applicable government regulations and local guidelines for
quality control.
▪ 11662970122, CleanCell, 6 x 380 mL measuring cell cleaning
solution Calculation
▪ 11930346122, Elecsys SysWash, 1 x 500 mL washwater additive The analyzer automatically calculates the analyte concentration of each
sample (either in ng/mL or µg/L).
▪ 11933159001, Adapter for SysClean
Interpretation of the results
▪ 11706802001, Elecsys 2010 AssayCup, 60 x 60 reaction vessels
When interpreting the test results the possibility of anti‑Tg antibodies in the
▪ 11706799001, Elecsys 2010 AssayTip, 30 x 120 pipette tips sample should be taken into account. Results should be either confirmed
Accessories for MODULAR ANALYTICS E170, cobas e 601 and with the confirmatory test (e.g. Elecsys Tg II Confirmatory Test) or
cobas e 602 analyzers: preferably verified by the determination of anti‑Tg (e.g. Elecsys Anti‑Tg
assay).1,2
▪ 04880340190, ProCell M, 2 x 2 L system buffer
Limitations - interference
▪ 04880293190, CleanCell M, 2 x 2 L measuring cell cleaning
solution The assay is unaffected by icterus (bilirubin < 1128 µmol/L or < 66 mg/dL),
hemolysis (Hb < 0.373 mmol/L or < 0.6 g/dL), lipemia (Intralipid
▪ 03023141001, PC/CC‑Cups, 12 cups to prewarm ProCell M and < 22.8 mmol/L or < 2000 mg/dL) and biotin (< 123 nmol/L or < 30 ng/mL),
CleanCell M before use IgG ≤ 2 g/dL, IgA ≤ 1.6 g/dL and IgM ≤ 0.5 g/dL.
▪ 03005712190, ProbeWash M, 12 x 70 mL cleaning solution for run Criterion: Recovery within ± 10 % of initial value for samples ≤ 2 ng/mL or
finalization and rinsing during reagent change ± 25 % of initial value for samples > 2 ng/mL.
▪ 03004899190, PreClean M, 5 x 600 mL detection cleaning solution

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Elecsys Tg II
Samples should not be taken from patients receiving therapy with high The Limit of Blank, Limit of Detection and Limit of Quantitation were
biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin determined in accordance with the CLSI (Clinical and Laboratory Standards
administration. Institute) EP17‑A2 requirements.
No interference was observed from rheumatoid factors up to a The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of
concentration of 600 IU/mL. analyte‑free samples over several independent series. The Limit of Blank
There is no high-dose hook effect at Tg concentrations up to corresponds to the concentration below which analyte‑free samples are
120000 ng/mL. found with a probability of 95 %.
In vitro tests were performed on 17 commonly used pharmaceuticals. No The Limit of Detection is determined based on the Limit of Blank and the
interference with the assay was found. standard deviation of low concentration samples. The Limit of Detection
corresponds to the lowest analyte concentration which can be detected
The following special thyroid drugs were tested with concentrations shown (value above the Limit of Blank with a probability of 95 %).
in the table below. No interference with the assay was found. Criterion:
Recovery within ± 10 % of initial value. The Limit of Quantitation is defined as the lowest amount of analyte in a
sample that can be accurately quantitated with a total allowable error of
Drug Concentration (μg/mL) ≤ 30 %.
Iodid 0.2 When reporting results below LoQ a higher uncertainty needs to be taken
into consideration.
Carbimazol 30
Dilution
Thiamazol 80 Samples with Tg concentrations above the measuring range can be diluted
Propylthiouracil 300 with Diluent MultiAssay. The recommended dilution is 1:10 (either
automatically by the MODULAR ANALYTICS E170, Elecsys 2010 or
Perchlorat 2000 cobas e analyzers or manually). The concentration of the diluted sample
Propranolol 240 must be > 50 ng/mL.
After manual dilution, multiply the result by the dilution factor.
Amiodaron 200
After dilution by the analyzers, the MODULAR ANALYTICS E170,
Prednisolon 100 Elecsys 2010 and cobas e software automatically takes the dilution into
Hydrocortison 200 account when calculating the sample concentration.
Fluocortolon 100 Expected values
3.5-77 ng/mL
Octreotid 0.3
These values correspond to the 2.5th and 97.5th percentiles of results
L-T3 0.5 obtained from a total of 478 healthy Caucasian subjects (254 males,
224 females).
D-T3 0.5
Each laboratory should investigate the transferability of the expected values
L-T4 5 to its own patient population and if necessary determine its own reference
D-T4 5 ranges.
In rare cases, interference due to extremely high titers of antibodies to Specific performance data
analyte‑specific antibodies, streptavidin or ruthenium can occur. These Representative performance data on the analyzers are given below.
effects are minimized by suitable test design. Results obtained in individual laboratories may differ.
Tg determinations can be affected by the presence of anti‑thyroglobulin Precision
antibodies (anti‑Tg) or by non‑specific effects in patient sera. Results Precision was determined using Elecsys reagents, pooled human sera and
should be either confirmed with the Tg recovery test (e.g. Elecsys Tg II controls in a protocol (EP5‑A2) of the CLSI (Clinical and Laboratory
Confirmatory Test) or preferably verified by the determination of anti‑Tg Standards Institute): 2 runs per day in duplication each for 21 days (n = 84).
(e.g. Elecsys Anti‑Tg assay).1,2 The following results were obtained:
MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers:
Elecsys 2010 and cobas e 411 analyzers
Make sure that in the Special Wash List (Screen → Utility → Special Wash
→ Immune) the Elecsys Tg II assay is combined with Anti‑Tg. Repeatability Intermediate
precision
From test Step To test Step 0 Step 1 Step 2
Sample Mean SD CV SD CV
Anti-Tg 1 Tg II - x -
ng/mL ng/mL % ng/mL %
The described additions to the Special Wash List have to be entered Human serum 1 0.180 0.010 5.5 0.017 9.2
manually. Please refer to the operator's manual.
For diagnostic purposes, the results should always be assessed in Human serum 2 1.11 0.024 2.2 0.034 3.0
conjunction with the patient’s medical history, clinical examination and other Human serum 3 1.59 0.019 1.2 0.042 2.6
findings.
Human serum 4 89.3 2.71 3.0 3.71 4.2
Limits and ranges
Measuring range Human serum 5 247 6.14 2.5 7.83 3.2
0.04‑500 ng/mL (defined by the Limit of Detection and the maximum of the Human serum 6 470 9.14 1.9 17.9 3.8
master curve). Values below the Limit of Detection are reported as PC Ub)1 20.8 0.421 2.0 1.08 5.2
< 0.04 ng/mL. Values above the measuring range are reported as
> 500 ng/mL (or up to 5000 ng/mL for 10‑fold diluted samples). PC U2 67.0 0.900 1.3 3.39 5.1
Lower limits of measurement b) PC U = PreciControl Universal
Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation
(LoQ)
Limit of Blank = 0.02 ng/mL
Limit of Detection = 0.04 ng/mL
Limit of Quantitation = 0.1 ng/mL with a total allowable error of ≤ 30 %

2017-09, V 3.0 English 3/4

Elecsys Tg II
MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers 11 Mazzaferri EL, Robbins RJ, Spencer CA, et al. A Consensus Report of
the Role of Serum Thyroglobulin as a Monitoring Method for Low-Risk
Repeatability Intermediate Patients with Papillary Thyroid Carcinoma. J Clin Endocrinol Metab
precision 2003;88:1433-1441.
Sample Mean SD CV SD CV 12 Zucchelli G, Iervasi A, Ferdeghini M, et al. Serum thyroglobulin
ng/mL ng/mL % ng/mL % measurement in the follow-up of patients treated for differentiated
thyroid cancer. Q J Nucl Med Mol Imaging 2009;53:482-489.
Human serum 1 0.289 0.014 4.8 0.017 5.9
13 Elisei R, Pinchera A. Advances in the follow-up of differentiated or
Human serum 2 1.10 0.028 2.5 0.050 4.5 medullary thyroid cancer. A Nat Rev Endocrinol 2012;8:466-475.
Human serum 3 1.56 0.031 2.0 0.062 4.0 14 Guder WG, Narayanan S, Wisser H, et al. List of Analytes;
Human serum 4 87.5 2.90 3.3 4.09 4.7 Preanalytical Variables. Brochure in: Samples: From the Patient to the
Laboratory. GIT-Verlag, Darmstadt 1996:20/21. ISBN 3-928865-22-6.
Human serum 5 242 5.85 2.4 10.4 4.3
15 Feldt-Rasmussen U, Profilis C, Colinet E, et al. Purification and
Human serum 6 456 10.4 2.3 19.8 4.3 assessment of stability and homogeneity of human thyroglobulin
reference material (CRM 457). Exp Clin Endocrinol 1994;102:87-91.
PC U1 19.5 0.419 2.2 0.896 4.6
16 Bablok W, Passing H, Bender R, et al. A general regression procedure
PC U2 61.1 1.20 2.0 2.52 4.1 for method transformation. Application of linear regression procedures
for method comparison studies in clinical chemistry, Part III.
Method comparison J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.
A comparison of the Elecsys Tg II assay (y) with a commercial assay (x)
using clinical samples gave the following correlations: For further information, please refer to the appropriate operator’s manual for
the analyzer concerned, the respective application sheets, the product
Number of samples measured: 94 information and the Method Sheets of all necessary components (if
available in your country).
Passing/Bablok16 Linear regression
A point (period/stop) is always used in this Method Sheet as the decimal
y = 0.936x + 0.105 y = 0.917x + 0.877 separator to mark the border between the integral and the fractional parts of
τ = 0.892 r = 0.981 a decimal numeral. Separators for thousands are not used.
The sample concentrations were between approximately 0.2 and Symbols
300 ng/mL. Roche Diagnostics uses the following symbols and signs in addition to
those listed in the ISO 15223‑1 standard (for USA: see
Analytical specificity https://usdiagnostics.roche.com for definition of symbols used):
The following cross‑reactivities were found, tested with thyroglobulin
concentrations of approximately 5 and 50 ng/mL: Contents of kit
Cross-reactant Concentration tested Cross-reactivity Analyzers/Instruments on which reagents can be used
% Reagent
TSH 1000 mIU/L 1.94 Calibrator
TBG 200000 ng/mL 0.008 Volume after reconstitution or mixing
References GTIN Global Trade Item Number
1 Erali M, Bigelow RB, Meikle AW. ELISA for thyroglobulin in serum:
recovery studies to evaluate autoantibody interference and reliability of COBAS, COBAS E, ELECSYS and PRECICONTROL are trademarks of Roche. INTRALIPID is a trademark of
thyroglobulin values. Clin Chem 1996;42(5):766-770. Fresenius Kabi AB.
All other product names and trademarks are the property of their respective owners.
2 Spencer CA, LoPresti JS. Technology Insigth: measuring thyroglobulin Additions, deletions or changes are indicated by a change bar in the margin.
and thyroglobulin autoantibody in patients with differentiated thyroid © 2017, Roche Diagnostics
cancers. Nat Clin Pract Endocrinol Metab 2008;4(4):223-233.
3 Clark P, Franklyn J. Can we interpret serum thyroglobulin results? Ann
Clin Biochem 2012;49:313–322.
4 Malthiéry Y, Lissitzky S. Primary structure of human thyroglobulin Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim
deduced from sequence of its 8448-base complementary DNA. Eur J www.roche.com
Biochem 1987;165:491-498.
5 Kronenberg HM, Melmed S, Polonsky KS, et al. Williams Textbook of
Endocrinology. Saunders Elsevier, Philadelphia, 12th edition, 2011.
6 Torréns JI, Burch HB. Serum thyroglobulin measurement. Utility in
clinical practice. Endocrinol Metab Clin North Am 2001;30(2):429-467.
7 Pacini F, Pinchera A. Serum and tissue thyroglobulin measurement:
Clinical applications in thyroid disease. Biochemie 1999;81:463-467.
8 Pacini F, Schlumberger M, Dralle H, et al. European consensus for the
management of patients with differentiated thyroid carcinoma of the
follicular epithelium. Eur J Endocrinol 2006;154:787–803.
9 Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid
Association Management Guidelines for Patients with Thyroid Nodules
and Differentiated Thyroid Cancer. Thyroid 2009;19(11):1-48.
10 Pitoia F, Ward L, Wohllk N, et al. Recommendations of the Latin
American Thyroid Society on diagnosis and management of
differentiated thyroid cancer. Arq Bras Endocrinol Metab
2009;53(7):884-897.

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