Undetectable Serum Thyroglobulin Due to Negative Interference of Heterophile Antibodies in Relapsing Thyroid Carcinoma

Giovanella, Luca; Ghelfo, Antonella

doi:10.1373/clinchem.2007.093229

Cited by 40 publications

(31 citation statements)

References 4 publications

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“…However, HAb may also bind to the capture antibody preventing the binding of analyte and/or detection antibody causing false negative or falsely low results (5). Accordingly, we observed a case of HAb-induced false negative Tg measurement in a patient with lymph-node metastases from DTC (7). Therefore, we decided to examine the prevalence of significant HAb interferences in our current Tg assay systematically by evaluating a large cohort of samples with all concentrations of Tg.…”

Section: Introductionmentioning

confidence: 99%

Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma

Giovanella¹,

Keller

Ceriani

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: To examine the prevalence of significant interference from heterophile antibodies (HAb) in the measurement of serum thyroglobulin (Tg), we evaluated a large cohort of samples from patients with differentiated thyroid carcinoma (DTC). Methods: Serum Tg measurements were performed in 406 serum samples before and after incubation of each serum sample in heterophile-blocking tubes (HBT) at room temperature for 1 h. We calculated the difference between the original Tg value and the value obtained after HBT treatment. We considered any sample showing an absolute percent difference )3 SD from the mean percent difference as being affected by HAb interference. Results: We identified five patients (1%) as showing interference from HAb. Of these, three (60%) showed a false positive or falsely increased Tg concentration without any recurrence following clinical work-up; two (40%) showed a false negative or falsely reduced Tg levels, and metastases were detected in both cases by imaging procedures. Conclusions: HAb may increase as well as reduce the measured Tg in a significant number of patients. A positive HAb interference should be suspected if Tg elevation does not fit the clinical pictures. A negative interference is a more challenging problem because increases in Tg generally occur as the first sign of recurrence of DTC. Therefore, treatment using HBT tubes of all sera referred for Tg measurement should be considered in order to prevent both unwarranted investigations or therapy, and delayed diagnosis of recurrence in patients affected by DTC. Clin Chem Lab Med 2009;47:952-4.

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Section: Introductionmentioning

confidence: 99%

Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma

Giovanella¹,

Keller

Ceriani

et al. 2009

Clinical Chemistry and Laboratory Medicine

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“…HAMA interference arises when antibodies that recognize murine proteins are present in the patient serum and interact with the capture and/ or labeled monoclonal antibody reagents. These reactions simulate the presence of thyroglobulin in the specimen, and can create a falsely elevated result and, rarely, a false-negative result (12,33). Our assay uses antibodies derived from rabbit (polyclonal) and mouse (monoclonal), which potentially decrease the interference by heterophilic antibodies, because it is more unusual that one patient has antibodies reacting against immunoglobulins from two different species.…”

Section: Discussionmentioning

confidence: 99%

“…HAMA is a potential problem for all immunometric assays, since most of them are based on monoclonal antibodies produced in mice. In the case of Tg assays, as in most other immunometric assays, the presence of HAMA can lead to false-positive (most of the time), or false-negative results (11,12). The potential presence of HAMA is still a challenge, but accumulated knowledge has paved the way to deal adequately with the phenomenon most of the time (13).…”

Section: Introductionmentioning

confidence: 99%

Development, characterization and clinical validation of new sensitive immunofluorometric assay for the measurement of serum thyroglobulin

Nakabashi

Biscolla

Kasamatsu

et al. 2012

Arq Bras Endocrinol Metab

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OBJECTIVE: In the last decade, data published stressed the role of highly-sensitive thyroglobulin (Tg) assays in the follow-up of differentiated thyroid carcinoma (DTC) patients. The present study describes a new, highly-sensitive Tg assay, compares it with an available commercial assay, and validates it in the follow-up of DTC patients. SUBJECTS AND METHODS: The immunofluorometric high-sensitivity Tg assay is based on monoclonal and polyclonal antibodies produced at our laboratories. It was validated in 100 samples of 87 patients with DTC submitted to total thyroidectomy, 87% of whom also received radioiodine. For correlation, all samples were also tested using a commercial Tg assay (Beckman Access) with functional sensitivity (FS) of 0.1 ng/mL. RESULTS: The new method showed FS of 0.3 ng/mL. The correlation between the two methods was good (r = 0.74; p < 0.0001). The diagnostic sensitivity was 88.9%, and it was increased to 100% when combined with neck US. CONCLUSION: This new, high-sensitivity Tg assay presented a good correlation with Beckman Access assay and with the clinical outcome of the patients. The continuous availability of a validated assay is an additional advantage for long term follow-up of DTC patients. Arq Bras Endocrinol Metab. 2012;56(9):658-65

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“…For IMA tests HAMA mainly produces a false increase (56) and more rarely false negative Tg values (57). One should consider interference caused by HAMA if the measured Tg concentration does not correspond to the patient's clinical status and, if possible, Tg in the presence of HAMA should be measured by RIA.…”

Section: Interference With Serum Factorsmentioning

confidence: 99%

Measuring Thyroglobulin Concentrations in Patients with Differentiated Thyroid Carcinoma

Savin¹,

Cvejić²,

Mijatović³

et al. 2010

Journal of Medical Biochemistry

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Kratak sadr`aj: Tiroidni karcinomi su naj~e{}i maligni endo krini tumori. Tireoglobulin (Tg), specifi~ni protein {ti -ta ste `lezde, najva`niji je tumorski marker u tireoidnoj onkologiji. Kod pacijenata sa diferentovanim karcinomima tireo ideje, nakon operativnog le~enja, koncentracija Tg odre|uje se radi otkrivanja rezidualnog tumorskog tkiva ili postojanja lokalnih, odnosno udaljenih metastaza. Na koncentraciju Tg u serumu uti~u: masa prisutnog tireoidnog tkiva (benignog ili malignog), intenzitet stimulacije receptora za tireostimuli{u}i hormon (TSH) i sposobnost tumorskih }elija da sinteti{u i lu~e Tg. Savremene metode, imunometrijske (IMA) i radioimunolo{ke (RIA), kojima se odre|uje koncentracija Tg u serumu ispitanika, imaju odre|ena ograni~enja koja mogu da umanje klini~ki zna~aj dobijenih rezultata. Usled metodolo{kih razlika, koncen tra cije Tg u istim uzorcima seruma, izmerene razli~itim testo vima, mogu se razlikovati. Faktori koji mogu prouzrokovati razlike u izmerenim koncentracijama Tg su brojni: razli~iti referentni materijali, razlike u specifi~nosti primarnih i sekundarnih antitela za antigenske determinante Tg, razli ~it afinitet vezivanja tih antitela za epitope Tg, i interfe ren cija serumskih faktora. Princip testa, kao i eventualno prisu stvo TgAt u serumima ispitanika, mo `e uticati na izmerenu koncentraciju Tg. Svako odstupanje izmerenih koncentra cija Tg od stvarnih vrednosti mo`e imati ozbiljne posledice: la`no niske vrednosti Tg mogu odlo`iti neophodni tretman pacijenata, dok la`no pove}ane vrednosti Tg mogu prouzrokovati nepotrebni stres, ili ~ak tretman pacijenata. I pored ograni~enih mogu}nosti savreme nih metoda, odre|ivanje koncentracije Tg u serumu pacije nata operisa nih od diferentovanog tiroidnog karcino ma je koristan test za otkrivanje pogor{anja bolesti i za pra}enje efekata tera pije.Klju~ne re~i: diferentovani tireoidni karcinom, imunometrijski test, tireoglobulin, tireoglobulinska antitela Summary: Thyroid carcinomas are the most common malignant endocrine tumors. Thyroglobulin (Tg), a specific thyroid protein, is the most important tumor marker in thyroid oncology. After total thyroidectomy or radioiodine therapy, detectable or increasing serum Tg levels in patients with differentiated thyroid carcinoma indicate persistence of active thyroid tissue or cancer recurrence. Serum Tg concentration primarily reflects three variables: the mass of differentiated thyroid tissue present; the degree of thyrotropin receptor stimulation and the intrinsic ability of the tumor to synthesize and secrete Tg. Measurement of serum Tg by current immunometric (IMA) and radioimmunological (RIA) assays encounters some methodological problems which can diminish its clinical importance. Discrepancy between the results for Tg using different methods may be caused by: different reference materials, specific properties of the primary and secondary antibodies for antigenic determinants on Tg and diverse binding affinities of these epitopes, together with interference by serum factors (usually antibo...

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Undetectable Serum Thyroglobulin Due to Negative Interference of Heterophile Antibodies in Relapsing Thyroid Carcinoma

Cited by 40 publications

References 4 publications

Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma

Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma

Development, characterization and clinical validation of new sensitive immunofluorometric assay for the measurement of serum thyroglobulin

Measuring Thyroglobulin Concentrations in Patients with Differentiated Thyroid Carcinoma

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