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Technical Briefs |
1
Lab. Univ. de Phys. Biol., URA CNRS 1173, Service de Méd. Interne, CHRU, Strasbourg, France;
2
Service Central de Méd. Nucléaire, Clin. Marc Linquette, CHRU, Lille, France;
3
Boehringer Mannheim, Tutzing, Germany;
a address for
correspondence: Inst. de Phys. Biol., Faculté de Méd., F-67085 Strasbourg Cedex, France: fax 33 3 88 14 48 79, e-mail sapin{at}alsace.u-strasbg.fr
Immunoassays on the fully automated Elecsys® 2010 analyzer (Boehringer Mannheim, Meylan, France) involve the electrochemiluminescent reaction of Ru(II) Tris(bipyridyl) with tripropylamine combined with a magnetic microparticle separation after short incubation times with low sample volumes [1]. The thyrotropin (TSH) assay, which requires a high sensitivity [2], has an 18-min incubation time and 50-µL sample volume. In the present study we assessed the analytical and clinical performances of this TSH assay during 5 weeks in June and July of 1996. Assays were performed in singleton according to the manufacturer's instructions with two different lot numbers. Results were compared with those of the Immulite TSH3G assay (Behring Diagnostic, Rueil Malmaison, France). The procedures were performed in accordance with the Helsinki Declaration of 1975, as revised in 1983.
Interassay reproducibility was assessed by repeated analysis (n = 12) of 12 patients' frozen sera and of the TSH3G Immulite control serum. CVs were <5% at TSH >0.06 mU/L, 10.4% at TSH of 0.018 mU/L, and 14.9% at TSH of 0.014 mU/L. "Functional sensitivity" (CV = 20%) was <0.014 mU/L; therefore Elecsys TSH can be considered a third-generation TSH assay (3). Carryover might be a problem with such an assay (4). Two samples with low TSH concentrations (<0.005 mU/L) were assayed immediately after a sample of high TSH concentration (191 mU/L). Carryover was <0.3:10 000 and so should not affect the precision profile (4). For practical purposes we adopted a lower working limit for the Elecsys TSH of 0.01 mU/L.
One serum (TSH = 100 mU/L) was diluted from twofold to 512-fold in universal diluent (Boehringer Mannheim) and one serum (1 mU/L) from twofold to 64-fold in a sample from a hyperthyroid patient (<0.005 mU/L). The linearity was satisfactory with found values 97–106% and 100–107% of expected, respectively.
Elecsys TSH results (y) from 318 samples were related to those obtained with the Immulite method (x) over the range 0.005–100 mU/L according to the equation: y = 1.18x - 0.08 (r = 0.981, Sy|x = 2.81). Over the range 0.005 to 1 mU/L (n = 153) the equation was: y = 1.15x + 0.005 (r = 0.974, Sy|x = 0.09). Results were significantly higher by the Elecsys method (P <0.001, Wilcoxon's matched pairs signed rank test).
Clinical results are shown in Fig. 1
. TSH was assayed in sera obtained from 102 euthyroid control
patients (51 ambulatory, 51 hospitalized; age range 16–75 years). Log
transformation of the data yielded a reference range (mean ± 2
SD) of 0.50–4.36 mU/L. TSH was >4.36 mU/L in 41 sera from patients
with hypothyroidism (35 overt and 6 subclinical) and <0.30 mU/L in 46
sera from patients with hyperthyroidism (33 overt and 13 subclinical).
We propose a reference range from 0.30 to 4.36 mU/L that, without
decreasing sensitivity for dysthyroidism, includes low normal TSH
values (5). In 31 euthyroid patients between 75 and 92
years of age, TSH was increased in two and decreased in three. Severe
nonthyroidal ill (NTI) patients (n = 68) may have transiently high
or low TSH (6)(7). In these samples Elecsys
and Immulite showed similar and satisfactory performances.
Specificities were respectively 100% vs 99% in euthyroid control
patients, 84% vs 81% in old patients, and 84% vs 85% in NTI
patients; sensitivities were 100% vs 100% in hyperthyroid patients
and 100% vs 97.5% in hypothyroid patients. In 13 patients receiving
L-thyroxine (l-T4) suppressive
doses for thyroid cancer treatment, TSH values were <0.30 mU/L
by both kits and well correlated (r = 0.964,
Sy|x = 0.029).
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In six sera from hyperthyroid patients, of which three contained heterophile antibodies, showing falsely increased TSH values as measured by another immunometric assay, Elecsys TSH was low, consistent with the clinical status of the patient. Interference seems to be very rare with this assay, which involves a chimeric (mouse/human) labeled antibody. In a serum from an euthyroid patient containing anti-avidin antibodies, Elecsys TSH was normal (2.0 mU/L), in agreement with the Immulite value (1.5 mU/L). Contrary to other methods also involving a streptavidin-coated solid phase (8), Elecsys TSH seems not to be disturbed by these antibodies. These lacks of interference are worth noting since, according to Laurberg (9), nonspecific TSH values are the most common cause of nonsuppressed TSH in hyperthyroidism and should be considered before other causes such as pituitary tumors or pituitary resistance to thyroid hormones.
In conclusion, the Elecsys TSH assay showed a high degree of reproducibility (third-generation TSH assay). It provided a clear separation between eu-, hyper-, and hypothyroid patients. Its specificity was also very satisfactory: lack of interference from heterophile antibodies or from less specific origin, no carryover. These characteristics tend to give to the Elecsys TSH a very good diagnostic potential and reinforce TSH as a cost-effective front-line thyroid function test.
Acknowledgments
We thank S. Doffoel from the MGEN Laboratory in Strasbourg for providing us the ambulatory control samples and Boehringer Mannheim France for the Elecsys 2010 analyzer as well as the corresponding reagents.
References
The following articles in journals at HighWire Press have cited this article:
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  J. Kratzsch, G. M. Fiedler, A. Leichtle, M. Brugel, S. Buchbinder, L. Otto, O. Sabri, G. Matthes, and J. Thiery New Reference Intervals for Thyrotropin and Thyroid Hormones Based on National Academy of Clinical Biochemistry Criteria and Regular Ultrasonography of the Thyroid Clin. Chem., August 1, 2005; 51(8): 1480 - 1486. [Abstract] [Full Text] [PDF]
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H. A. Hendriks, W. Kortlandt, and W. M. Verweij Standardized Comparison of Processing Capacity and Efficiency of Five New-Generation Immunoassay Analyzers Clin. Chem., January 1, 2000; 46(1): 105 - 111. [Abstract] [Full Text] [PDF]
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M. A. Navarro, T. Palencia, M. R. Bonnin, and P. Rosel Daily BlankCell Procedure in Elecsys 2010 Improves the Reproducibility of Thyrotropin, Free Thyroxine, and Triiodothyronine Clin. Chem., August 1, 1998; 44(8): 1772 - 1773. [Full Text] [PDF]
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