Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma.
01 Apr 1998-The Journal of Clinical Endocrinology and Metabolism (Endocrine Society)-Vol. 83, Iss: 4, pp 1121-1127
TL;DR: The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC and may be an additional clinically useful tumor marker parameter for following T gAb- positive patients.
Abstract: 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.
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University of Colorado Boulder1, Harvard University2, Mayo Clinic3, Boston University4, University of Pennsylvania5, University of Pittsburgh6, University of Siena7, University Health Network8, Institut Gustave Roussy9, Oregon Health & Science University10, University of Texas MD Anderson Cancer Center11, Duke University12, University of Cincinnati13, Memorial Sloan Kettering Cancer Center14, MedStar Washington Hospital Center15
TL;DR: Evidence-based recommendations are developed to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer and represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...
10,501Â citations
Cites background or methods from "Serum thyroglobulin autoantibodies:..."
...Thus, serial serum anti-Tg antibody quantification using the same methodology may serve as an imprecise surrogate marker of residual normal thyroid tissue, Hashimoto thyroiditis, or tumor (608;609;615)....
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...recurrence/persistent disease associated either with a new appearance of antithyroglobulin antibodies or rising titers (609-614)....
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Johns Hopkins University1, University of Michigan2, University of Colorado Denver3, Ohio State University4, Boston University5, University of Pennsylvania6, University of Florida7, Mayo Clinic8, University of Siena9, Institut Gustave Roussy10, University of Cincinnati11, Memorial Sloan Kettering Cancer Center12
TL;DR: Evidence-based recommendations in response to the appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...
7,525Â citations
Cites background or methods from "Serum thyroglobulin autoantibodies:..."
...In 1996, the American Thyroid Association (ATA) published treatment guidelines for patients with thyroid nodules and DTC (10)....
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...Recommendation rating: E [B6] What is the appropriate operation for indeterminate thyroid nodules and DTC?...
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...In addition, for patients with nodules diagnosed as DTC by FNA during pregnancy, delaying surgery until after delivery does not affect outcome (104)....
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...Recommendation rating: C [C10] What is the role of thyroxine TSH suppression during thyroid hormone therapy in the long-term follow-up of DTC?...
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...The presence of these antibodies usually interferes with serum Tg measurement and recovery assays do not appear to accurately predict this interference (305,428)....
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Johns Hopkins University School of Medicine1, University of Michigan2, Anschutz Medical Campus3, Ohio State University4, Boston Medical Center5, University of Pennsylvania6, University of Florida7, Mayo Clinic8, University of Texas MD Anderson Cancer Center9, Memorial Sloan Kettering Cancer Center10
2,086Â citations
Cites background from "Serum thyroglobulin autoantibodies:..."
...The use of recovery assays for this purpose is controversial (184,198)....
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...The presence of these antibodies usually interferes with serum thyroglobulin measurement and recovery assays do not appear to accurately predict this interference (198,295)....
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...Serial serum antithyroglobulin antibody measurements may serve as an imprecise surrogate marker of residual normal thyroid tissue or tumor (198,199)....
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...Antithyroglobulin antibodies are a common clinical problem in patients with differentiated thyroid carcinoma (20%) (198)....
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01 Jan 2014
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.
1,988Â citations
TL;DR: The approach to treatment of papillary and follicular cancer is usually very similar, and DTC is more likely to be completely resected and ablated with iodine-131 (I), an approach that has become more popular in the past several decades when discovered at an early stage.
Abstract: Papillary and follicular thyroid cancer, together referred to as differentiated thyroid cancer (DTC), is usually curable when discovered at an early stage. Its management, however, is often a challenge because there have been no prospective randomized trials of treatment and none are likely to be done, given its typically prolonged course and relative infrequency. Instead, clinicians rely on large patient cohort studies in which therapy has not been randomized, leading to some disagreement about management. Nonetheless, thyroid cancer mortality rates have fallen significantly (20%, P , 0.05) in the United States between 1973 and 1996 (1), almost certainly due to early diagnosis and effective treatment of DTC, which comprises 90% of thyroid cancers and 70% of the thyroid cancer deaths (2). The decline in mortality, however, occurred only in women (1), perhaps because they undergo routine medical examinations more than men, in whom thyroid cancer is typically discovered at an older age (1). DTC is more likely to be completely resected and ablated with iodine-131 (I), an approach that has become more popular in the past several decades, when discovered at an early stage (3, 4). Much of the following discussion refers to treatment of DTC because the approach to treatment of papillary and follicular cancer is usually very similar.
1,302Â citations
References
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TL;DR: The results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.
Abstract: We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.
507Â citations
TL;DR: The data support the thesis that in differentiated thyroid carcinoma serum thyroglobulin levels are elevated when metastases develop after initial treatment and represent a simple and valuable adjunct in the posttreatment follow up of patients with differentiated thyroid cancer.
Abstract: 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.
288Â citations
"Serum thyroglobulin autoantibodies:..." refers background in this paper
...ERUM thyroglobulin (Tg) is an established tumor marker used in the management of patients with a diagnosis of differentiated thyroid carcinoma (DTC) ( 1 , 2). However, a number of technical problems impair the clinical utility of this test....
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TL;DR: Physicians need to consider a number of factors before selecting a laboratory to perform Tg measurements in patients with differentiated thyroid carcinoma, including assay sensitivity, as judged by the discrimination between lower limit of the euthyroid range and the functional sensitivity limit, as well as assay specificity, especially with respect to serum TgAb interference.
197Â citations
Additional excerpts
...differentiated thyroid carcinoma (DTC) (1, 2)....
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TL;DR: Lymphocytic infiltration surrounding the tumor or inside the tumor in PTC might be of use as a means for predicting a favorable prognosis and class II or class III patients with no lymphocytic infiltrate had a high rate of recurrence.
Abstract: Ninety-five patients with papillary thyroid carcinoma (PTC) who received primary surgical treatment in 1983 at Kuma Hospital and were followed until 1992 were the subjects of this study. Initial therapy was tumor resection for 5 patients, lobectomy for 23 patients, total thyroidectomy with unilateral modified neck dissection for 60 patients, and total thyroidectomy with bilateral modified neck dissection for 7 patients. Clinical stage at diagnosis was as follows. Class I included 28 patients with intrathyroidal disease, class II included 60 patients with positive cervical lymph nodes, and class II included 7 patients with tumor invasion into tissue outside of the thyroid gland. Recurrence of the tumor was evaluated according to lymphocytic infiltration in the thyroid gland. Group A consisted of 36 patients with PTC associated with lymphocytic infiltration, 26 with infiltration surrounding the tumor, 3 with infiltration inside of the tumor, and 7 with both. Group B consisted of the remaining 59 patients with PTC with no lymphocytic infiltration. There were no differences in age, sex, initial tumor size, or initial treatment between groups A and B. Antithyroglobulin antibody and/or antimicrosomal antibody were positive in 16 patients from group A and 4 patients from group B (P < 0.001). Class I included 14 patients from each group, class II included 22 patients from group A and 38 patients from group B, and class III included 7 patients, all from group B. Recurrence of the tumor was found in only 1 group A patient (2.8%), but in 11 patients of group B (18.6%). The percentage of patients free from recurrence over the 10 yr of follow-up in group A was significantly higher than that in group B (by Cox-Mantel test, P < 0.01). The time between initial treatment and recurrence was 2-10 yr. In comparing the clinical stage at the time of initial treatment, recurrence was found in 1 class II patient from group A (4.5%) and in 1 class I (7.1%), 6 class II (15.8%), and 4 class III (57.1%) patients from group B. No patients died during the 10 yr of follow-up. In conclusion, 1) lymphocytic infiltration surrounding the tumor or inside the tumor in PTC might be of use as a means for predicting a favorable prognosis; and 2) class II or class III patients with no lymphocytic infiltration had a high rate of recurrence.
189Â citations
"Serum thyroglobulin autoantibodies:..." refers background in this paper
...One study reports a correlation among lymphocytic infiltration, serum thyroid autoantibodies, and a favorable long term outcome (18)....
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TL;DR: Optimal performance goals are recommended for manufacturers developing and laboratories and physicians selecting a serum Tg method to use for serial long-term monitoring of thyroid cancer patients.
Abstract: Serum thyroglobulin (Tg) measurements are used as a tumor marker for monitoring patients with differentiated thyroid carcinoma. The clinical utility of six different Tg methods [RIA or immunometric assay (IMA)] currently used in Europe and the US was evaluated, with focus on methodologic standardization, sensitivity, interassay precision across the typical clinical monitoring interval (6 to 12 months), "hook" effects (IMA methods), and Tg autoantibody interference. The methods evaluated were: DYNOtest Tg (Henning), OptiQuant Tg (Kronus), SELco Tg (Medipan), Thyroglobulin IRMA (Pasteur), Nichols Chemiluminescent ICMA (Corning Nichols), and an RIA developed by us (USC Endocrine Services Laboratory). The clinical impact of the current methodologic problems on the use of serum Tg measurements is reviewed. Optimal performance goals are recommended for manufacturers developing and laboratories and physicians selecting a serum Tg method to use for serial long-term monitoring of thyroid cancer patients.
179Â citations
"Serum thyroglobulin autoantibodies:..." refers background in this paper
...detecting hook effects have recently been published (3)....
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...and Tg autoantibody (TgAb) interference (3)....
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