Determination of Serum-Thyroglobulin by a Hæmagglutination-Inhibition Test

375

113

A B S T R A C T A specific and reproducible double antibody radioimmunoassay for the measurement of thyroglobulin (HTg) in human serum has been developed. Since antithyroglobulin autoantibodies combine with the ["3'I] HTg tracer, antibody-positive sera were rejected for measurement. Specificity is demonstrated in that thyroid analogous such as thyroxine (T4), triiodothyronine (T3) monoiodotyrosine (MIT) and diiodotyrosine (DIT) did not crossreact. Sera previously reacted with anti-HTg-Sepharose contained no immunoassayable HTg. Finally, sera obtained from patients after total thyroid ablation for thyroid carcinoma did not contain demonstrable HTg. The sensitivity of the assay is 1.6 ng/ml, and HTg was detectable in 74% of 95 normal subjects. The mean concentration was 5.1 ng/ml ±0.49 SEM (range < 1.6-20.7 ng/ml). Day to day variation in HTg levels is large in some euthyroid subjects and nearly absent in others. HTg was detectable in 90% of the sera obtained in 23 pregnant women at delivery in whom a mean concentration of 10.1 ng/ml ±1.3 SEM was observed. The mean level for the corresponding newborn infants at birth was 29.3 ng/ml ±4.7 SEM a value significantly higher than the mean maternal HTg concentration (P < 0.001). A group of 17 thyrotoxic individuals all had elevated HTg levels; the mean for this group was 344.8 ng/ml ±90.7 SEM. In the acute phase of subacute thyroiditis HTg was also elevated in all of 12 patients, and the mean for this group was 136.8 ng/ml ±74.6 SEM.

Section: Serum Samplementioning

confidence: 99%

Radioimmunoassay for Measurement of Thyroglobulin in Human Serum

Herle¹,

Uller²,

Matthews³

et al. 1973

375

113

“…From the studies of Hjort (1), Assem (2), and Roitt and Torrigiani (3), it became clear that the occurrence ofTG is not restricted to the thyroid gland but appears also in the circulation of vertebrates at species-specific concentrations (4-6).…”

Section: Introductionmentioning

confidence: 99%

Extrathyroidal release of thyroid hormones from thyroglobulin by J774 mouse macrophages.

Brix

Herzog²

1994

Thyroglobulin appears in the circulation of vertebrates at species-specific concentrations. We have observed that the clearance of thyroglobulin from the circulation occurs in the liver by macrophages. Here we show that the thyroid hormones T3 and T4 were released by incubation of mouse macrophages (J774) with thyroglobulin. Thyroid hormone release was a fast process, with an initial rate of -20 pmol T4/mg per min and 0.6 pmolT3/mg per min, indicating that macrophages preferentially release T4. The bulk of released thyroid hormones appeared after 5 min ofincubation ofmacrophages with thyroglobulin, whereas degradation of the protein was detectable only after several hours. During internalization ofthyroglobulin, endocytic vesicles and endosomes were reached at 5 min and lysosomes at 60 min. T4 release started extracellularly by secreted proteases and continued along the endocytic pathway of thyroglobulin, whereas T3 release occurred mainly intracellularly when thyroglobulin had reached the lysosomes. This shows that the release of both hormones occurred at distinct cellular sites. Our in vitro observations suggest that macrophages in situ represent an extrathyroidal source for thyroid hormones from circulating thyroglobulin. (J. Clin. Invest. 1994Invest. .93:1388Invest. -1396

“…Several previous investigations cast serious doubts on the theory that thyroglobulin is a secluded antigen confined to the thyroid gland in man (1)(2)(3). In recent years data showing the presence of thyroglobulin in blood were extended to studies in patients with various pathologic states of the thyroid gland (4,5).…”

Section: Introductionmentioning

confidence: 99%

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

Herle¹,

Uller²

1975

269

A B S T R A C T The presence of human thyroglobulin (HTg) in serum of patients with differentiated thyroid carcinoma was studied. The thyroglobulin detected in the serum of such 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 statistically 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.