Antithyroglobulin antibodies in patients with differentiated thyroid carcinoma: methods of detection, interference with serum thyroglobulin measurement and clinical significance

Abstract

Antithyroglobulin antibodies (TgAb) were measured using a chemiluminescent immunoassay (ICMA) and an agglutination test. TgAb laboratory and clinical interference with Tg measurements were assessed. The course of TgAb concentration and disease status were compared during 3 years after initial treatment. The agglutination test failed to detect all titers < 10IU/mL (ICMA). Interference from TgAb was common at high titers, but even low antibody titers (< 5IU/mL) were able to interfere with Tg measurement. Cases of distant metastases with undetectable Tg (by IRMA) and those apparently free of disease and without thyroid remnants with Tg> 2ng/ml (by RIA) were identified among patients with TgAb. The exogenous Tg recovery test was normal (> 80%) by the two methods in 22% of patients with TgAb and confirmed laboratory interference. Absence of reduction in TgAb levels was a marker of persistent disease. In conclusion, TgAb should be determined by immunoassays; interference with Tg measurements occurred mainly but not always at high concentrations, with a normal Tg recovery test not excluding this interference. The behavior of TgAb is related to disease persistence or cure. Anticorpos anti-tireoglobulina (TgAb) foram medidos por um imunoensaio de quimioluminescência (ICMA) e um teste de aglutinação. Avaliamos a interferência clínica e laboratorial dos TgAb com as medidas de Tg. A evolução da concentração dos TgAb e o estado da doença foram comparados durante 3 anos após o início do tratamento. O teste de aglutinação falhou em detectar todos o títulos <10UI/mL (ICMA). Interferência dos TgAb foi comum com títulos altos, mas mesmo títulos baixos dos anticorpos (<5UI/mL) interferiram na medida de Tg. Casos com metástases à distância e Tg indetectável (por IRMA) e aqueles aparentemente livres da doença e sem remanescentes tireoidenos com Tg >2ng/ml (por RIA) foram identificados entre pacientes com TgAb. O teste de recuperação da Tg exógena foi normal (>80%) por ambos os métodos em 22% dos pacientes com TgAb, confirmando a interferência laboratorial. Ausência de redução dos níveis de TgAb foi um marcador de persistência da doença. Em conclusão, TgAb deve ser determinada por imunoensaios; interferência com as medidas de Tg ocorreram principalmente mas não somente em altas concentrações, com um teste normal de recuperação de Tg não excluindo esta interferência. O comportamento dos TgAb está relacionado à persistência ou à cura da doença.

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

“…Whatever the factors responsible for the different methods reporting different values, this study emphasized that a change in TgAb method would severely disrupt the use of TgAb concentrations as a surrogate tumor marker and that this problem could not be overcome by deriving between-method conversion factors (1,4,9,15). Given the high prevalence of TgAb in DTC found in this (23.8%) and other studies, it is critical to ensure that specimens do not contain TgAb before authenticating a serum Tg result because even low levels of TgAb can interfere with Tg measurement (4,6,21,26). Direct TgAb measurement is generally recommended in preference to an exogenous Tg recovery test because studies have shown that Tg recoveries do not reliably detect the presence of interfering TgAb (1,6,8,14,26,37,39).…”

“…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).…”

“…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). The current study used a low Tg IMA to Tg RIA ratio (below the 2.5th percentile for TgAb negative controls) to indicate the presence of TgAb interference.…”

Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Taskforce

“…The presence of these antibodies usually interferes with serum thyroglobulin measurement and recovery assays do not appear to accurately predict this interference (198,295). Decreasing antibody levels are correlated with "disease-free" status while increasing levels suggest persistent disease (199,296).…”

Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus

“…4. The presence of TgAb in the serum can elicit false low Tg results in immunometric assays (136). Therefore, investigation of TgAb is mandatory, Figure 2.…”