Interference in thyroid‐stimulating hormone determination

Marco Balerna

Interference in thyroid‐stimulating hormone determination

Marco Balerna

2010, European Journal of Clinical Investigation

visibility

…

description

3 pages

link

1 file

Eur J Clin Invest 2010; 40 (8): 756–758Background Thyroid‐stimulating hormone (TSH) measurement plays a major role in the diagnosis of thyroid disorders. Despite the good quality of immunochemical tests measuring TSH levels, the presence of interfering substances can sometimes alter the TSH results.Design We reported the case of a 79‐year‐old man affected by primary autoimmune hypothyroidism hospitalized for pneumonia. A TSH value > 100 mIU L‐1 (reference: 0.44 mIU L‐1) was found at admission. No signs and symptoms of hypothyroidism were found upon clinical examination and serum concentration of the free thyroxine (FT4) was normal.Results Serum treatment in heterophile antibody blocking tubes did not change the TSH result in our assay, while normal levels were found in a different immunoassay method. An abnormal pattern was found in protein electrophoresis at admission, with IgG / j and IgM / k monoclonal bands proved in immunofixation. Interestingly, the disappearance of mono...

DOI: 10.1111/j.1365-2362.2010.02315.x BRIEF COMMUNICATION Interference in thyroid-stimulating hormone determination Mauro Imperiali*, Paola Jelmini*, Biagio Ferraro*, Franco Keller*, Roberto della Bruna*, Marco Balerna* and Luca Giovanella† * Ente Ospedaliero Cantonale, Bellinzona, Switzerland, †Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland ABSTRACT Background Thyroid-stimulating hormone (TSH) measurement plays a major role in the diagnosis of thyroid disorders. Despite the good quality of immunochemical tests measuring TSH levels, the presence of interfering substances can sometimes alter the TSH results. Design We reported the case of a 79-year-old man affected by primary autoimmune hypothyroidism hospitalized for pneumonia. A TSH value > 100 mIU L-1 (reference: 0.44 mIU L-1) was found at admission. No signs and symptoms of hypothyroidism were found upon clinical examination and serum concentration of the free thyroxine (FT4) was normal. Results Serum treatment in heterophile antibody blocking tubes did not change the TSH result in our assay, while normal levels were found in a different immunoassay method. An abnormal pattern was found in protein electrophoresis at admission, with IgG / j and IgM / k monoclonal bands proved in immunofixation. Interestingly, the disappearance of monoclonal bands was paralleled with a normalization of the TSH value. Conclusions We suggest in this study that the TSH determination might be influenced by the presence of transient paraproteins. Keywords Interference, monoclonal gammopathy, TSH. Eur J Clin Invest 2010; 40 (8): 756–758 Thyroid-stimulating hormone (TSH) measurement in blood is the most reliable test to diagnose all common forms of hypoand hyperthyroidism, particularly in outpatients. However, stress, drugs, nutritional status, chronic or acute diseases as well as heterophile antibodies might interfere with the TSH measurement. We report in this study the case of a 79-year-old man hospitalized for pneumonia. At admission, C-reactive protein (CRP) level was 53 mg L)1 (reference < 5 mg L)1), procalcitonin (PCT) 0Æ65 lg L)1 (reference < 0Æ25 lg L)1), creatinine 128 lmol L)1 (reference < 107 lmol L)1) with an estimated glomerular filtration rate (eGFR) of 47 mL min)1 1Æ73 m)2 (reference 88–180 mL min)1 1Æ73 m)2), ASAT 205 U L)1 (reference < 41 U L)1), ALAT 93 U L)1 (reference < 41 U L)1), c-GT 327 U L)1 (reference < 61 U L)1), total bilirubin 28Æ5 lmol L)1 (reference < 19 lmol L)1) and direct bilirubin 15Æ3 lmol L)1 (reference < 8Æ6 lmol L)1). A homogeneous shadowing of the middle and lower lobe of the right lung was found by chest X-ray examination; liver and kidneys were normal in ultrasound examination. Antibiotic and 756 European Journal of Clinical Investigation Vol 40 support therapies (i.e. intravenous fluids, oxygen therapy) were started and pneumonia progressively resolved; the patient was then transferred from medicine department to rehabilitation clinic (day +12) and finally dismissed (day +44) with a CRP of 15 mg L)1, creatinine of 151 lmol L)1 with an estimated glomerular filtration rate (eGFR) of 39 mL min)1 1Æ73 m)2, ASAT of 22 U L)1, ALAT of < 10 U L)1 and total bilirubin of 11Æ3 lmol L)1. The patient was under thyroxine (Euthyrox; Merck Schweiz AG, Zug, Switzerland) treatment (75 lg pro diem) because of autoimmune hypothyroidism (i.e. autoimmune thyroiditis, AIT). Consequently, the serum TSH was measured at admission (3rd generation HYPERSENSITIVE hTSH, UniCel DxC 880i platform; Beckman-Coulter, Nyon, Switzerland); a significant increase at > 100 mIU L)1 (reference 0Æ4–4 mIU L)1) was found. A typical explanation for elevated TSH in an elderly patient on thyroid hormone replacement is hypothyroidism as a result of noncompliance with thyroxine substitution at home. However, serum free-thyroxine (FT4) concentration was found to be in the upper third of the reference interval in our patient INTERFERENCE IN TSH DETERMINATION (18Æ8 pmol L)1; reference 7Æ5–21Æ1 pmol L)1), as expected in adequately treated patients who are clinically euthyroid [1]. In addition, serum FT4 value measured in our laboratory 6 months before hospitalization on a UniCel DxC 880i platform was 19Æ2 pmol L)1, with a corresponding serum TSH of 0Æ586 mIU L)1. Critical illness is characterized by multiple abnormalities in thyroid homoeostasis (i.e. nonthyroid illnesses, NTI). The most prominent alterations are low serum triiodothyronine (T3) and elevated reverse T3 (rT3), leading to the general term low T3 syndrome, while serum TSH levels are generally normal or reduced. Accordingly, serum FT3 was measured in our patient and a normal level was found (4Æ00 pmol L)1; reference 3Æ80– 6Æ00 pmol L)1). Looking at these data, both suboptimal compliance and NTI were unlike in our patient. An interference in TSH measurement was then hypothesized and the serum TSH (day +1) with result of TSH > 100 mIU L)1 was retested in another immunological method (Architect i2000SR; Abbott Diagnostic, Zug, Switerland). In this study, a normal serum TSH level was found (0Æ43 mIU L)1; reference 0Æ27–4Æ2 mIU L)1) suggesting a method-specific interference on TSH measurement by Beckman-Coulter UniCel DxC 880i platform. Immunological methods are known to be prone to false positive or negative results because of the presence of heterophilic antibodies [2]. A patient’s sample, pre-treated with the heterophilic blocking reagent (HBT, Scantibodies Laboratory, Santee, CA, USA) to get rid of heterophilic antibodies, was re-analysed % of variation in repeated TSH measurements TSH (mIU mL–1) (a) (b) on UniCel DxC 880i platform. No differences were found in results obtained before and after serum treatment in HBT, excluding interferences caused by heterophilic antibodies. The TSH was then monitored over a period of 44 days by performing sequential TSH measurements in duplicate on UniCel DxC 880i platform. While initial values were increased and showed a great variability (i.e. > 200%), a progressive reduction in TSH levels was observed over time, with a corresponding trend in analytical variability (Fig. 1a). A pathological protein electrophoresis pattern with IgG ⁄ j and IgM ⁄ k monoclonal bands in immunofixation was found in sera obtained at admission (Fig. 1b). Interestingly, both TSH value and TSH variability were simultaneously normalized with the disappearance of the monoclonal bands in electrophoresis (Fig. 1b). Despite a reduced variability rate, an isolated spike in TSH concentration still occurred on day 15. At that moment however, the TSH value of 33Æ1 mIU L)1 decreased to 2Æ05 and 2Æ43 mIU L)1 after 2-fold and 4-fold dilution with suppressed human serum respectively. In addition, a TSH value of 2Æ79 mIU L)1 was measured on Architect i2000SR (Abbott Diagnostic), that is in line with the value found on the Beckman platform after dilution. Globally, our data suggest a method-specific transient interference on the TSH measurement on UniCel DxC 880i platform as a result of a transient paraproteinemia. Paraproteins induction because of infectious disease has been already Electrophoresis (top) and immunofixation (bottom) on day 1 of hospitalization 100 80 60 40 20 Electrophoresis on the last day of hospitalization (day 40) 4 g L–1 300 200 100 0 10 20 30 Days after hospitalization 40 ELP G A M K L Figure 1 (a) Mean of 2 TSH measurements as well as percentage of variation in the TSH determination are shown (Beckman intraseries variability data from 2Æ49% to 5Æ83% for TSH levels ranging between 28Æ60 and 0Æ027 mIU L)1 respectively). (b) Electrophoresis and immunofixation on the first day of hospitalization showing pathological protein electrophoresis pattern are shown. As comparison, a normal electrophoresis performed during the last day of hospitalization is reported. Arrow indicates the quantification of the monoclonal peak. European Journal of Clinical Investigation Vol 40 757 M. IMPERIALI ET AL. described in the literature [3,4]. Accordingly, monoclonal bands were present at admission while disappeared with the resolution of pneumonia in our patient. From literature it is also known that paraproteins can interfere with immunometric methods [5]. Monoclonal IgA proved to interfere with the determination of total T3 and T4 but not with TSH measurement [5]. However, Ross et al., recently reported two cases of antibodies interfering with TSH measurement. In one of these cases, the addition of heterophilic blocking reagent to the sample was not sufficient for the correction of the interference but an abnormal peak of the IgM-immunoglobulin was present. Removal of IgM antibodies was correlating with a prompt normalization of the TSH level [6]. This case strictly resembles that of our patient; in our case, however, the TSH normalization occurred after spontaneous disappearance of the monoclonal peaks. This highlights that a transient paraproteinemia might be a source of interference during the determination of TSH levels. As heterophilic antibodies treatment is not always successful, it is important to underline the role of clinical informations, retesting in different assays and dilution test to give the most reliable TSH results for patients with clinically inappropriate results. Acknowledgements We would like to warmly thank the clinicians and the nurses of the Department of Internal medicine of the Ospedale Civico di Lugano for the collaboration in collecting the blood samples. Disclosures ⁄ conflict of interest The authors declare that they have no competing interests. Author contributions MI drafted the manuscript and conceived the study. PJ drafted the manuscript. BF carried out the immunoassay. FK drafted www.ejci-online.com the manuscript and conceived the study. RDB drafted the manuscript and conceived the study. MB drafted the manuscript and conceived the study. LG drafted the manuscript and conceived the study. Address EOLAB-Dipartimento di Medicina di Laboratorio, Ente Ospedaliero Cantonale, Bellinzona, Switzerland (M. Imperiali, P. Jelmini, B. Ferraro, F. Keller, R. della Bruna, M. Balerna); Divisione di Medicina Nucleare e Centro Malattie Tiroidee, Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland (L. Giovanella). Correspondence to: Luca Giovanella, MD, Divisione di Medicina Nucleare e Centro Malattie Tiroidee, Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland. Tel.: +41-91-811 86 72; fax: +41-91-811 82 50; e-mail: [email protected] Received 11 December 2009; accepted 23 April 2010 References 1 Demers CM, Spencer CA. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003;13:1–95. 2 Tate J, Ward G. Interferences in immunoassay. Clin Biochem Rev 2004;25:105–20. 3 Sève P, Turner R, Stankovic K, Perard L, Broussolle C. Transient monoclonal gammopathy in a patient with Bartonella quintana endocarditis. Am J Hematol 2006;81:115–7. 4 Strobel SL. Transient paraproteinemia: an intriguing immunological anomaly. Ann Clin Lab Sci 2003;33:265–70. 5 Cissewski K, Faix JD, Reinwein D, Moses AC. Factitious Hyperthyroxinemia due to a monoclonal IgA in a case of multiple myeloma. Clin Chem 1993;39:1739–42. 6 Ross HA, Menheere PPCA, Thomas CMG, Mudde AH, Kouwenberg M, Wolffenbuttel BHR. Interference from heterophilic antibodies in seven current TSH assays. Ann Clin Biochem 2008;45:616–8. 758 ª 2010 The Authors. Journal Compilation ª 2010 Stichting European Society for Clinical Investigation Journal Foundation

Log In

Interference in thyroid‐stimulating hormone determination

Related papers

Related papers

Related topics