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      Prognostic Value of Basal Serum Thyroglobulin Levels, but Not Basal Antithyroglobulin Antibody (TgAb) Levels, in Patients with Differentiated Thyroid Cancer Translated title: Diferansiye Tiroid Kanserli Hastalarda Bazal Antitiroglobülin Antikorunun (TgAb) Değil, Bazal Tiroglobülin Düzeylerinin Prognostik Değeri

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          Abstract

          Objective: The prognostic values of serum thyroglobulin (Tg) and antithyroglobulin antibody (TgAb) levels, measured immediately before I-131remnant ablation in patients with differentiated thyroid cancer (DTC), have been advocated by some researchers; however, it had controversial outcomes. This study was carried out to examine this dilemma and to check the clinical significance of basal serum Tg and TgAb levels and postablation iodine 131whole body scan(WBS) findings in DTC patients.

          Methods: In this retrospective study, the records of 500 patients with differentiated thyroid cancer, who had undergone treatment between 2003 and 2010, were assessed. Of those, 149 patients with results of basal serum thyroglobulin concentration and whole body scan using radioactive iodine were included. Age, sex, tumour histology, basal thyroglobulin (Tg), anti-thyroglobulin (TgAb) and TSH concentration, radioactive iodine doses in each hospitalization, numbers of hospitalization, and results of whole body scans were recorded. The relationship among basal Tg, TgAb, TSH, and whole body scan with hospitalization number and total radioactive iodine doses were assessed.

          Results: A total of 149 patients, including 123 (83%) females and 26 (17%) males, with a mean age of 40±15 years, took part in the study. The mean (SD) basal Tg, TgAb, and TSH were 91.7±169.2 ng/mL (0.1-1000 ng/mL), 250±893 U/mL (0-9000 U/m L), and 64.8±61.5 µU/mL (30-689 U/mLµ), respectively. A total of 52 (34.9%) cases had TgAb levels greater than 100 U/mL. The mean basal Tg in patients who were admitted three or more times was significantly greater than that of patients with one hospitalization (p=0.026). In addition, the mean of Tg in patients who received 7.4 GBq radioactive iodine or less was significantly lower than the others (p=0.003). The mean of TgAb and TSH were not different between these groups. In the results of the whole body scans, patients with metastasis had higher frequency of hospitalization (p=0.010) and received higher radioactive iodine levels (p<0.001).

          Conclusions: The findings of this study showed that, in differentiated thyroid cancer, lower basal serum Tg levels and absence of metastasis in radioiodine scan after ablation treatment were correlated with fewer hospitalizations and lower doses of radioactive iodine. Basal TgAb and TSH had no relation. Therefore, it seems that basal Tg could help us in determining which patients need aggressive treatment.

          Translated abstract

          Amaç: Diferansiye tiroid kanserli (DTK) hastalarda I-131 ile rezidü ablasyonundan hemen önce ölçülen serum tiroglobulin (Tg) ve antitiroglobulin antikoru (TgAb) düzeylerinin prognostik değeri bazı araştırıcılar tarafından ileri sürülmekle beraber, tartışmalı sonuçlar mevcuttur. Bu çalışma, DTK’li hastalarda bu ikilemi incelemek ve bazal serum Tg ve TgAb düzeylerinin ve ablasyon sonrası I-131 tüm vücut tarama bulgularının klinik önemini araştırmak için planlandı.

          Yöntem: Bu retrospektif çalışmada 2003 ve 2010 yılları arasında tedavi alan DTK’lı 500 hastanın kayıtları incelendi. Bu hastalar arasından bazal serum Tg konsantrasyonu ve radyoaktif iyot ile tüm vücut tarama sonuçları olan 149 hasta dahil edildi. Yaş, cinsiyet, tümör histolojisi, bazal Tg, TGAb ve TSH konsantrasyonları, her yatıştaki radyoaktif iyot dozu, yatış sayısı ve tüm vücut tarama sonuçları kaydedildi. Bazal Tg, TGAb, TSH ve tüm vücut tarama ile yatış sayısı ve toplam radyoaktif iyot dozu arasındaki ilişki araştırıldı.

          Bulgular: Yaş ortalaması 40±15 olan, 123 (%83) kadın ve 26 (%17) erkek olmak üzere toplam 149 hasta çalışmaya alındı. Ortalama (SD) bazal Tg, TgAb ve TSH değerleri, sırasıyla 91,7±169,2 ng/mL (0,1–1000 ng/mL), 250±893 U/mL (0-9000 U/m L) ve 64,8±61,5 µU/mL (30-689 U/mLµ) idi. Toplam 52 (%34,9) hastanın TgAb düzeyleri 100 U/mL den yüksekti. Üç ya da daha fazla sayıda yatış yapılan hastaların ortalama bazal Tg düzeyleri, tek yatış yapılan hastalardan anlamlı olarak yüksekti (p=0,026). Ayrıca, 7,4 GBq ya da daha az radyoiyot alan hastaların ortalama Tg değerleri diğerlerine göre anlamlı olarak daha düşüktü (p=0,003). Ortalama TgAb ve TSH gruplar arasında farklılık göstermiyordu. Tüm vücut tarama sonuçlarına göre, metastazlı hastalarını hastaneye yatış frekansları daha yüksekti ve daha yüksek radyoaktif iyot alımı mevcuttu (p<0,001).

          Sonuç: Bu çalışmanın bulguları, diferansiye tiroid kanserinde, düşük bazal serum Tg düzeyleri ve ablasyon sonrası radyoiyot taramada metastaz olmamasının daha az hastaneye yatış sayısı ve daha düşük radyoaktif iyot dozları ile korele olduğunu gösterdi. Bazal TgAb ve TSH korelasyon göstermedi. Bu nedenle, bazal Tg hangi hastaların agresif tedaviye gereksinim duyduğunu belirlemede yardımcı olabileceği düşünüldü.

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          Most cited references21

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

          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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            Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens.

            The development of antibodies to thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone (TSH) receptor is a main feature of autoimmune thyroid diseases. To investigate whether complete removal of thyroid antigens results in the abatement of humoral thyroid autoimmunity. Retrospective chart review study of patients treated and monitored with a standard prospective protocol. University hospital in Pisa, Italy, between 1976 and 1994. 182 patients with differentiated thyroid carcinoma and serum antibodies to thyroid peroxidase, thyroglobulin, or TSH receptor due to coexistent clinical Hashimoto thyroiditis, Graves disease, or focal autoimmune thyroiditis. Total thyroidectomy and radioiodine treatment to ablate residual or metastatic thyroid tissue. Regular follow-up with iodine-131 whole-body scanning and serum thyroglobulin measurement. Mean follow-up (+/-SD) was 10.1 +/- 4.1 years (range, 4 to 20 years). Serum antibodies to thyroid peroxidase, thyroglobulin, and TSH receptor. Thyroid peroxidase, thyroglobulin, and TSH-receptor antibodies progressively disappeared after the initial treatment. The median disappearance time was 6.3 years for thyroid peroxidase antibodies and 3.0 years for thyroglobulin antibodies. There was a statistically significant correlation between the disappearance of thyroid tissue and that of thyroid antibodies. The coexistence of Hashimoto thyroiditis or Graves disease with thyroid cancer did not modify the pattern of disappearance of thyroid antibody compared with patients with focal autoimmune thyroiditis. Complete ablation of thyroid tissue with its antigenic components results in the disappearance of antibodies to all major thyroid antigens, thus supporting the concept that continued antibody production depends on the persistence of autoantigen in the body.
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              Change of serum antithyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma.

              The aim of the study was to evaluate the usefulness of the antithyroglobulin autoantibody (TgAb) value at 6-12 months after remnant ablation in predicting recurrence in differentiated thyroid carcinoma patients who had undetectable thyroglobulin (Tg) values. The change in TgAb concentration measured between the time of remnant ablation (TgAb1) and 6-12 months thereafter (TgAb2) was also evaluated as a possible prognostic indicator. Patients with differentiated thyroid carcinoma who underwent total thyroidectomy followed by (131)I remnant ablation between 1995 and 2003 at the Asan Medical Center (Seoul, Korea) were enrolled. Of these, 824 patients with undetectable Tg at 6-12 months after remnant ablation during thyroid hormone withdrawal were the subjects of this study. TgAb2 was positive in 56 patients. Ten of 56 patients (18%) with positive TgAb2 had recurrence, whereas only 10 of 768 patients (1%) with negative TgAb2 had recurrence during 73.6 months of follow-up (P < 0.001). The change between TgAb1 and TgAb2 levels was evaluated in patients with positive TgAb2. TgAb concentration decreased by more than 50% in 21 patients (group 1) and by less than 50% in 16 patients (group 2), and it increased in 19 patients (group 3). The recurrence rates in groups 1, 2, and 3 were 0, 19, and 37%, respectively (P = 0.016). Serum TgAb levels measured at 6-12 months after remnant ablation could predict recurrence in patients with undetectable Tg values. In patients with undetectable Tg and positive TgAb values, a change in TgAb concentration during the early postoperative period may be a prognostic indicator of recurrence.
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                Author and article information

                Journal
                Mol Imaging Radionucl Ther
                Mol Imaging Radionucl Ther
                MIRT
                Molecular Imaging and Radionuclide Therapy
                Galenos Publishing
                2146-1414
                2147-1959
                June 2014
                5 June 2014
                : 23
                : 2
                : 54-59
                Affiliations
                [1 ] Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Department of Nuclear Medicine, Tehran, Iran
                [2 ] Golestan University of Medical Sciences (GUOMS), Golestan Research Center of Gastroenterology and Hepatology (GRCGH), Gorgan, Iran
                [3 ] Bushehr University of Medical Sciences, The Persian Gulf Nuclear Medicine Research Center, Bushehr, Iran
                Author notes
                * Address for Correspondence: Bushehr University of Medical Sciences, The Persian Gulf Nuclear Medicine Research Center, Bushehr, Iran GSM: 0098-771-2580169 E-mail: assadipoya@ 123456yahoo.com
                Article
                1219
                10.4274/mirt.39200
                4067877
                24963446
                5c9b7cb3-75ab-4058-abd2-ca2fc4b91c56
                © Molecular Imaging and Radionuclide Therapy, Published by Galenos Publishing.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 May 2013
                : 30 January 2014
                Categories
                Original Article

                thyroid cancer,thyroglobulin,anti-thyroglobulin
                thyroid cancer, thyroglobulin, anti-thyroglobulin

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