Comparison of the influence of thyroglobulin antibodies on serum thyroglobulin values from two different immunoassays in post surgical differentiated thyroid carcinoma patients

Stanojević-Pirković, Marijana; Savin, Svetlana; Cvejić, Dubravka; Djukic, Aleksandar; Jeremic, Marija; Zivancevic-Simonovic, Snezana

doi:10.1002/jcla.20339

Cited by 24 publications

(15 citation statements)

References 26 publications

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“…Tg has been reported to be method dependent (56)(57)(58), and the interassay variation can vary between 43% and 65% in healthy subjects (35,57,59). To overcome interassay variation and allow for comparisons between studies, a certified Tg reference material (i.e., CRM-457) has been produced as a quality-control material for assay standardisation (60).…”

Section: Methods To Measure Tg Concentrationmentioning

confidence: 99%

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Feei

Skeaff²

2014

Thyroid

133

110

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Background: Thyroglobulin, produced exclusively by the thyroid gland, has been proposed to be a more sensitive biomarker of iodine status than thyrotropin or the thyroid hormones triiodothyronine and thyroxine. However, evidence on the usefulness of thyroglobulin (Tg) to assess iodine status has not been extensively reviewed, particularly in pregnant women and adults. Summary: An electronic literature search was conducted using the Cochrane CENTRAL, Web of Science, PubMed, and Medline to locate relevant studies on Tg as a biomarker of iodine status. Since urinary iodine concentration (UIC) is the recommended method to assess iodine status in populations, only studies that clearly reported both Tg and UIC were included. For the purpose of this review, a median Tg <13 lg/L and a median UIC ‡100 lg/L (UIC ‡150 lg/L for pregnant women) were used to indicate adequate iodine status. We excluded studies conducted in subjects with either known thyroid disease or those with thyroglobulin antibodies. The search strategy and selection criteria yielded 34 articles of which nine were intervention studies. The majority of studies (six of eight) reported that iodine-deficient pregnant women had a median Tg ‡13 lg/L. However, large observational studies of pregnant women, including women with adequate and inadequate iodine status, as well as well-designed intervention trials that include both Tg and UIC, are needed. In adults, the results were equivocal because iodine-deficient adults were reported to have median Tg values of either <13 or ‡13 lg/L. Only studies in school-aged children showed that iodine-sufficient children typically had a median Tg <13 lg/L. Some of the inconsistent results may be partially explained by the use of different methodological assays and failure to assess assay accuracy using a certified reference material. Conclusions: These data suggest that Tg does hold promise as a biomarker of iodine deficiency. However, it is associated with limitations. A median Tg cutoff of 13 lg/L warrants further investigation, particularly in adults or pregnant women, as there is a lack of both observational and intervention studies in these groups.

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Section: Methods To Measure Tg Concentrationmentioning

confidence: 99%

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Feei

Skeaff²

2014

Thyroid

133

110

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“…Although assays are calibrated against the same International Reference Preparation [World Health Organization (WHO) first international reference preparation 65/93], the values reported by different methods are highly variable because of TgAb heterogeneity among patients, compounded by assay sensitivity and specificity differences (4,6,(17)(18)(19)(20)(21). Over recent years it has become apparent that serial TgAb concentrations can be monitored as a surrogate tumor marker (4,9,10,15,(22)(23)(24)(25)(26)(27)(28)(29). Because TgAb concentrations reported by different methods can vary 100-fold for the same specimen, it is critical to use the same method to monitor changes in TgAb concentrations (6,17,19,22).…”

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confidence: 99%

“…Previous studies have suggested that Tg RIA methodology is more resistant to TgAb interference than IMA, although interference causing falsely low or high serum Tg RIA values can occur in some TgAb-positive patients (1,6,23,24). Irrespective of whether the Tg IMA or RIA result is valid for any given serum, one recognized hallmark of TgAb interference is discordance between the Tg IMA vs. Tg RIA values (low/undetectable Tg IMA vs. higher/detectable Tg RIA) (4,6,25,26).…”

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confidence: 99%

Current Thyroglobulin Autoantibody (TgAb) Assays Often Fail to Detect Interfering TgAb that Can Result in the Reporting of Falsely Low/Undetectable Serum Tg IMA Values for Patients with Differentiated Thyroid Cancer

Spencer¹,

Petrović²,

Fatemi³

2011

The Journal of Clinical Endocrinology & Metabolism

151

112

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Many specimens with interfering TgAb were misclassified as TgAb negative using manufacturer-recommended cutoffs. It is recommended that assay AS limits be used to detect TgAb to minimize false-negative misclassifications. However, for two of four assays, AS limits failed to detect interfering TgAb in 20-30% of cases. TgAb methods were too qualitatively and quantitatively variable to establish conversion factors that would allow a change in method without disrupting serial TgAb monitoring.

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“…Thus, determining Tg in the same serum sample in different laboratories can give different values. Factors causing differences in the serum concentrations of Tg obtained using diffe rent tests are numerous: different reference materials, non-harmonized standards for the same reference material, different specificity and also the affinity of primary and secondary antibodies for Tg epitopes, interference of serum factors, primarily thyroglobulin autoantibodies (39-41) with pri mary and secondary TgAb in the diagnostic kits (42)(43)(44)(45). These differences between methods do not allow comparison of results and practically prevent interpretation of changes in Tg levels noted using different methods, such as changes in tumor size or the appearance of metastatic tissue.…”

Section: Methodological Problems In Determining Tgmentioning

confidence: 99%

“…Interpretation of TgAb concentra tions as a surrogate tumor marker is possible if tests from the same manufacturer are used during the monitoring of a patient, if possible in the same laboratory. Despite standardization according to the international reference material, MRC 65/93, commercial tests for TgAb have different sensitivities, specificities and measured absolute values (45,46,59,69,73), most probably due to differences in test specificities for different conformation epitopes of TgAb (69,71,74). A declining trend for TgAb over a long time period is a good sign of treatment efficacy (surgery/radioiodine ablation).…”

Section: Measuring Tgab In Serummentioning

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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Comparison of the influence of thyroglobulin antibodies on serum thyroglobulin values from two different immunoassays in post surgical differentiated thyroid carcinoma patients

Cited by 24 publications

References 26 publications

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Current Thyroglobulin Autoantibody (TgAb) Assays Often Fail to Detect Interfering TgAb that Can Result in the Reporting of Falsely Low/Undetectable Serum Tg IMA Values for Patients with Differentiated Thyroid Cancer

Measuring Thyroglobulin Concentrations in Patients with Differentiated Thyroid Carcinoma

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