The prevalence of circulating thyroid autoantibodies (TgAb or antithyroid peroxidase) was increased nearly 3-fold in patients with differentiated thyroid cancers (DTC) compared with the general population (40% vs. 14%, respectively). Serum TgAb (with or without antithyroid peroxidase) was present in 25% of DTC patients and 10% of the general population. Serial postsurgical serum TgAb and serum Tg patterns correlated with the presence or absence of disease. Measurements of serum Tg were made in 87 TgAb-positive sera by a RIA and two immunometric assay (IMA) methods to study TgAb interference. TgAb interference, defined as a significant intermethod discordance (>41.7% coefficient of variation) between the Tg RIA and Tg IMA values relative to TgAb-negative sera, was found in 69% of the TgAb-positive sera. TgAb interference was characterized by higher Tg RIA vs. IMA values and was, in general, more frequent and severe in sera containing high TgAb concentrations. However, some sera displayed marked interference when serum TgAb was low (1-2 IU/mL), whereas other sera with very high TgAb values (>1000 IU/mL) displayed no interference. An agglutination method was found to be too insensitive to detect low TgAb concentrations (1-10 IU/mL) causing interference. Exogenous Tg recovery tests were an unreliable means for detecting TgAb interference. Specifically, the exogenous Tg recovered varied with the type and amount of Tg added and the duration of incubation employed. Further, recoveries of more than 80% were found for some sera displaying gross serum RIA/IMA discordances. The measurement of serum Tg in DTC patients with circulating TgAb is currently problematic. It is important to use a Tg method that provides measurements that are concordant with tumor status. IMA methods are prone to underestimate serum when TgAb is present, increasing the risk that persistent or metastatic DTC will be missed. The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC. Furthermore, as serial serum TgAb measurements paralleled serial serum Tg RIA measurements, TgAb concentrations may be an additional clinically useful tumor marker parameter for following TgAb-positive patients. Disparities between serial serum Tg and TgAb measurements might alert the physician to the possibility of TgAb interference with the serum Tg measurement and prompt a more cautious use of such data for clinical decision-making.

/pdf/serum-thyroglobulin-autoantibodies-prevalence-influence-on-yhz00gbdsc.pdf

Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma.

The presence of human thyroglobulin (HTg) in serum of patients was identical by immunological criteria to the serum standard used in the radioimmunoassay. The serum thyroglobulin levels in untreated patients with differentiated thyroid carcinoma ranged from 22.0 to 445.0 ng/ml with a mean of 144.3 +/- 46.5 ng/ml (SEM) (n = 10). The mean serum thyroglobulin measured postoperatively in seven of these patients was 6.4 +/- 1.5 ng/ml, not statistacally different from the mean level of 5.1 +/- 0.49 ng/ml (range 0-20.7 ng/ml) observed in 71 out of 95 control subjects with detectable HTg levels. By contrast serum HTg levels were normal or undetectable in subjects with medullary carcinoma of the thyroid. HTg levels were within normal limits in sera of patients who had previously undergone successful therapy for a differentiated thyroid carcinoma and in whom no metastases could be documented. The mean level for this group was 4.9 +/- 0.51 ng/ml (n = 43). In contrast, patients with documented metastases had a mean serum thyroglobulin level of 464.9 +/- 155.6 ng/ml (n = 6). The data support the thesis that in differentiated thyroid carcinoma serum thyroglobulin levels are elevated when metastases develop after initial treatment. It is proposed that the measurement of thyroglobulin in the serum represents a simple and valuable adjunct in the posttreatment follow-up of patients with differentiated thyroid cancer.

/pdf/elevated-serum-thyroglobulin-a-marker-of-metastases-in-1rnabvl7b4.pdf

Elevated serum thyroglobulin. A marker of metastases in differentiated thyroid carcinomas.

(Second of Two Parts) Circulating Thyroglobulin For several decades, thyroglobulin was thought to be confined to the thyroid gland. This view can no longer be defended since thyroglobulin has unque...

Control of Thyroglobulin Synthesis and Secretion

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

This study was designed to investigate quantitatively the interference of thyroglobulin autoantibodies in the RIA of human thyroglobulin (hTG). Anti-hTG autoantibodies were combined with purified hTG to produce samples with known antibody titers and hTG concentrations. These samples were analyzed in the RIA. By using anti-human globulin serum it was first shown that immune complexes formed between labeled hTG and human anti-hTG. It was then shown that the most important factor in determining the direction of the interference was the specificity of the precipitating (second) antiserum with respect to these immune complexes. When the precipitating antiserum was specific, i.e. did not recognize human antibodies, the immune complexes remained in the supernatant and the measured hTG concentration was falsely elevated. When the precipitating antiserum cross-reacted with human antibodies, the direction of the interference depended on the sample volume. At small volumes there was false depression while at large volumes there was false elevation of apparent hTG levels, depending on the capacity of the precipitating antiserum to combine with human antibodies. Anti-hTG titers far below those detected by the tanned-red cell hemagglutination test had very large effects, to the point where measurements of hTG could not be made, when a cross-reactive precipitating antiserum was used. Therefore, the procedure which investigators have used until now, to exclude samples with anti-hTG hemagglutination titers above an arbitrary limit, is not adequate. It is necessary, until methods are developed which avoid the problem of autoantibody interference, to characterize each assay to determine the limits of anti-hTG that can be tolerated. The factors which influence anti-hTG interference in the hTG RIA are 1) the specificity of the precipitating antiserum, 2) the sample volume, 3) the maximum tracer binding, and 4) the anti-hTG titer.

Radioimmunoassay of human thyroglobulin: effect of antithyroglobulin autoantibodies.

A radioimmunoassay for the detection of thyroglobulin in human serum having a sensitivity of 10 ng/ml is described showing that conventional techniques can be applied to the assay of large globular proteins. In 60% of normal sera the assay was positive. The serum of athyreotic cretins gave negative results. The active material exhibited the same behavior as native thyroglobulin when assayed at multiple dilutions and when subjected to ultracentrifugation and electrophoresis; furthermore, it could be absorbed out with insoluble preparations of rabbit or human antithyroglobulin antibodies. It was concluded that the assay was specific for thyroglobulin and that this protein is commonly present in an undegraded form in normal human serum. The implications of these findings are discussed in relation to theories of auto-immunity. (Endocrinology 81: 421, 1967)

Identification and estimation of undegraded thyroglobulin in human serum.

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Identification and estimation of undegraded thyroglobulin in human serum.