Thyroid cysteine proteinases that catalyze release of thyroxine from thyroglobulin and thyroxine-containing peptide
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Thyroglobulin
Thyroglobulin immunometric "sandwich" assays (IMA) have taken over competitive radioimmunoassays, but this assay remains problematic. A human thyroglobulin reference material (CRM 457) has been prepared but is not widely used. That constitutes the main cause of very marked between kit variability of thyroglobulin results. High-dose hook effect, which can falsely decrease the result of a serum with high concentration of thyroglobulin, is not exceptional in one-step assays and should be systematically checked. Selection of monoclonal antibodies with no cross-reactivity with anti-thyroglobulin autoantibodies or of polyclonal antibodies with very high affinity, have reduced the frequency of interference due to autoantibodies, but did not abolish it. Recovery test is used to detect such interference, but with insufficient sensitivity. In fact, recovery determination can be influenced by the nature of thyroglobulin added to the serum (not identical to endogenous thyroglobulin), by the delay of incubation of exogenous thyroglobulin and serum autoantibodies and by the amount of added thyroglobulin. In addition, recovery is often wrongly expressed as the observed/theoretic ratio of final concentrations instead of added concentrations. In untreated Graves' disease patients and despite normal recovery test, thyroglobulin measured by IMA is lower when anti-thyroglobulin autoantibodies are present. Consequently, thyroglobulin result should be interpreted in function of presence or absence of autoantibodies. Development of total (free and autoantibody bound) thyroglobulin assay would be useful to evaluate assay and recovery test performances.
Thyroglobulin
Polyclonal antibodies
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Thyroglobulin
Sodium dodecyl sulfate
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Thyroglobulin measurement is useful for the follow up of patients subjected to total thyroidectomy for differentiated thyroid carcinoma. Thyroglobulin autoantibodies may interfere with its determination.To measure thyroglobulin autoantibodies and their interference with thyroglobulin determination.The presence of thyroglobulin autoantibodies was investigated in 801 serum samples sent to the laboratory for measurement of thyroglobulin levels. A serum was considered positive for these autoantibodies when radioactivity corresponding to 125I-thyroglobulin bound to thyroglobulin autoantibodies, precipitated with human gamma globulin, exceeded in 1.4 times that of a negative sera pool. In positive sera, thyroglobulin autoantibody concentration was measured and its interference with thyroglobulin radioimmunoassay was assessed through a recuperation test using exogenous thyroglobulin.Thyroglobulin autoantibodies were detected in 149 sera (18.6%). Of these, 65 had a recuperation that fluctuated between 1 and 80%. Thyroglobulin autoantibody concentration was negatively correlated with recuperation percentages (r = -0.64; p < 0.001) but not with thyroglobulin concentrations (r = 0.08). Thyroglobulin was higher in positive sera with a recuperation over 80% than in sera with a recuperation of less than 80% (12.7 +/- 1.7 and 5.9 +/- 0.6 ng/ml, respectively; p < 0.001).Thyroglobulin autoantibodies interfere with thyroglobulin measurement by radioimmunoassay, sequestering variable amounts of thyroglobulin. The presence of these autoantibodies must be investigated prior to thyroglobulin determination.
Thyroglobulin
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Thyroglobulin
Pathogenesis
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High concentration of thyroglobulin antibodies (TgAb) is a major limiting factor of thyroglobulin measurements in patients with differentiated thyroid cancer. We investigated whether thyroglobulin antibody added to serum samples could interfere with the thyroglobulin assay. Thyroglobulin levels in serum samples with different concentrations of thyroglobulin were measured by electrochemiluminescence immunoassay before and after the addition of increasing concentrations of thyroglobulin antibody using the secondary calibrator solution of the thyroglobulin assay kit containing sheep thyroglobulin antibody to reach thyroglobulin antibody levels within or near to the reference range. Thyroglobulin and thyroglobulin antibody concentrations were also measured in 134 serum samples from 27 patients after thyroid ablation. There was a strong negative association (slope = -1.179) between thyroglobulin antibody and thyroglobulin concentrations in samples with added thyroglobulin antibody (beta = -0.86; P < 0.001). Changes in thyroglobulin concentrations were described mathematically as loss of thyroglobulin% = -0.2408 x Ln(thyroglobulin antibody IU/ml) + 0.1944. Thyroglobulin concentrations were significantly lower than those calculated from experiments with added thyroglobulin antibody in 26/134 samples from patients after thyroid ablation. We conclude that if the same TgAb interference exists in the presence of naturally occurring human TgAb, our observation may prove to be useful during follow-up of patients with differentiated thyroid cancer. However, further studies are needed to explore the clinical relevance of thyroglobulin antibody levels within or near to the reference range in monitoring these patients.
Thyroglobulin
Reference range
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Thyroglobulin
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Thyroglobulin
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We have studied human thyroglobulin of extremely low iodine content obtained from a goitrous cretin who had no measurable peroxidase activity in his thyroid gland. Thyroglobulin from these patients is of interest because of the possibility that poorly iodinated thyroglobulin is particularly susceptible to dissociation and proteolysis. In the present study our data indicated that poorly iodinated thyroglobulin isolated under conditions inhibiting proteolysis possessed properties similar to normal human thyroglobulin in its secondary, tertiary, and quaternary structures.
Thyroglobulin
Proteolysis
Thyroid peroxidase
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