| Home | E-Submission | Sitemap | Contact Us |  
Korean J Intern Med > Volume 33(6); 2018 > Article
Jo and Lim: Clinical implications of anti-thyroglobulin antibody measurement before surgery in thyroid cancer

Abstract

Thyroglobulin antibody (TgAb) is a class G immunoglobulin and a conventional marker for thyroid autoimmunity. From a clinical perspective, TgAb is less useful than thyroid peroxidase antibodies for predicting thyroid dysfunction. However, TgAb is found more frequently in differentiated thyroid cancer (DTC) and can interfere with thyroglobulin (Tg) measurements, which are used to monitor the recurrence or persistence of DTC. Recent studies suggested a small but consistent role for preoperative TgAb in predicting DTC in thyroid nodules, and in reflecting adverse tumor characteristics or prognosis, including lymph node metastasis, but this is still controversial. Postoperative TgAb can serve as a biomarker for remnant thyroid tissue, so follow-up measures of TgAb are useful for predicting cancer recurrence in DTC patients. Since high serum TgAb levels may also affect the fine needle aspiration washout Tg levels from suspicious lymph nodes of DTC patients, it is important to use caution when interpreting the washout Tg levels in patients who are positive for TgAb.

INTRODUCTION

Differentiated thyroid cancer (DTC) is the most common endocrine cancer, and its incidence has been increasing worldwide. DTC is found in 7% to 15% of thyroid nodules, and it has a good prognosis [1]. The most common type of DTC is papillary thyroid cancer (PTC), comprising more than 90% of all thyroid cancers, whereas follicular thyroid cancer is less common, comprising 7% to 8% of thyroid cancers in Korea [2,3]. Lobectomy or total thyroidectomy is generally the treatment of choice, except for some microcarcinomas. After thyroidectomy, thyroid hormone replacement and radioactive iodine (RI) for remnant ablation are administered [4].
Serum thyroglobulin (Tg) is the most sensitive established biomarker of DTC after total thyroidectomy and RI. Tg is produced only in normal thyroid tissue or in thyroid cancer tissue, so measuring Tg levels in the blood is useful for the early detection of recurrent or residual disease in DTC patients who have undergone total thyroidectomy and RI. Disease-free individuals have extremely low Tg levels.
Tg levels could be affected by the presence of thyroglobulin antibody (TgAb), which falsely lowers or elevates serum Tg levels [5,6]. Thus, current cancer management guidelines mandate that Tg testing should always include the measurement of TgAb. Generally, an elevated TgAb level alone rarely indicates any specific disease states or changes, except during the post-operative follow-up of DTC patients with positive TgAb levels. However, studies have shown that the clinical use of TgAb has the potential to improve patient care. In this article, we summarize the ways that TgAb is being used in a variety of clinical settings in the thyroid cancer field.

CHARACTERISTICS OF TgAb

There are many thyroid-related antibodies that target specific proteins within or around the thyroid follicular cells, including thyroid peroxidase (TPO), thyroid-stimulating hormone (TSH) receptor, Tg, and, rarely, carbonic anhydrase 2, megalin, triiodothyronine, thyroxine, sodium iodide symporter (NIS), and pendrin [7]. Thyroid-related antibodies are usually related to thyroid autoimmune diseases: TPO antibodies (TPOAb) and TgAb indicate Hashimoto’s thyroiditis (HT), and TSH receptor antibodies indicate Graves’ disease (GD).
TgAb was the first antibody found in patients with autoimmune thyroid disease (AITD) as described by Doniach and Roitt in 1956 [8,9]. Most TgAbs are classified as immunoglobulin G (IgG), though some are IgA. It is an intra-follicular antibody that can bind to immune cells and antigens with or without tissue destruction. Massive destruction of the thyroid gland induces structural changes in Tg, leading to antibody production against Tg. Major T-cell epitopes on Tg require iodination for recognition by autoreactive T-cells [10]. This explains the higher incidence of positive TgAb levels in patients with an excessive iodine intake [11]. However, high Tg levels in blood do not necessarily induce antibody production. The TgAb level depends on antigen exposure time [7]. There are nearly 40 Tg epitopes, of which only a few are immunogenic [12]. TgAb itself does not cause thyroid cell destruction, and it does not fix complement because the epitopes are too widely spaced to allow cross-linking [13].

TgAb AND DTC

Studies have suggested that TgAb plays a role in the relationship between autoimmune thyroiditis and thyroid cancer; most of these studies have been pathological studies, though some are serological studies [14-16]. However, it is unclear what roles the thyroid autoantibodies that indicate thyroiditis play in the pathogenesis of thyroid cancer [7].
The prevalence of TgAb is approximately 1.5-fold higher in patients with DTC than in the general population with benign nodules (30.8% vs. 19.6%) [17]. TgAb is found more frequently in patients with PTC than in patients with follicular carcinomas [18]. Interestingly, the patterns of TgAb differ between patients with AITD and non-AITD patients, including those with DTC. Latrofa et al. [12] used human recombinant TgAb-Fab to investigate TgAb recognition in sera from patients with non-AITD thyroid diseases (nontoxic multinodular goiter and PTC) and AITD (HT and GD). They found that region A is the major immunodominant region of Tg, because the highest levels of inhibition were induced by TgAb-Fab of region A in all patients (> 50%) regardless of AITD. The inhibition levels were significantly higher in AITD patients than in non-AITD patients [12].

PREOPERATIVE TgAb AS A PREDICTOR OF THYROID CANCER

Positive serum TgAb is more than twice as prevalent in DTC patients than in the general population (25% vs. 10%) [14]. While TPOAb are believed to fix complement and can be used to diagnose HT and hypothyroidism more accurately than TgAb, TgAb may be more tumor-specific than TPOAb [19]. In particular, high TgAb levels can weakly predict thyroid carcinomas in patients with thyroid nodules, unlike TPOAb [17].
One study retrospectively evaluated a total of 2088 patients with thyroid nodules who received fine needle aspiration (FNA), and found that thyroid cancer was significantly associated with positive TgAb (odds ratio [OR], 1.61) [17]. A similar result was obtained by Vasileiadis et al. [20], who found that in patients who received a total thyroidectomy for any reason, preoperative measurements found TgAb more frequently in patients with malignant disease than in those with benign disease (38.2% vs. 19.8%). In another study of 2,562 patients who underwent FNA cytology (FNAC), suspicious cytology was detected more frequently in TgAb-positive patients than in those without TgAb (9.4% vs 5.7%), and isolated TgAb was a mild risk factor for thyroid cancer (OR, 1.74) [21]. Hosseini et al. [22] grouped patients according to TgAb level and found out that the prevalence of malignancy was higher in the positive TgAb group (65.38% vs. 50.42%). Qin el al. [23] also grouped patients according to TgAb level (0, 4, 11, 40, 100, and 500 IU/mL), and found that the prevalence of DTC was significantly higher in the high TgAb groups (≥ 100 IU/mL) than in the low TgAb groups (< 100 IU/mL).
However, when thyroid autoantibodies were considered as a marker for AITD, there was no significant difference in thyroid malignancy rates between AITD and non-AITD groups. Anil et al. [24] recruited patients with newly diagnosed thyroid nodules and evaluated thyroid autoantibodies before FNA. The FNA results revealed no differences in malignancy rates between the non-AITD and AITD groups. However, AITD patients were positive for at least one thyroid autoantibody, so this study could not detect the effects of TgAb alone on malignancy rates. Rago et al. [25] found similar results, but they also did not distinguish between TgAb and TPOAb.
Overall, these results suggest that unlike TPOAb, TgAb could be a weak but confident predictive marker for PTC in patients presenting with thyroid nodules (Table 1) [17,20-23,26-30]. TgAb may detect newly developed epitopes of Tg derived from thyroid cancer cells. Tg from benign follicular cells may be unlikely to develop any novel cancer-specific epitopes. The predictive value of TgAb for thyroid cancer before FNA is not very powerful and is controversial; therefore, other clinical parameters should be combined with TgAb to increase the diagnostic power of TgAb.

PREOPERATIVE TgAb LEVELS IN PREDICTING THE PROGNOSIS OF THYROID CANCER

It is generally accepted that thyroid cancer with AITD has a more favorable prognosis compared to thyroid cancer without AITD [14,16,31]. Most studies, however, have not examined the effects of TPOAb or TgAb separately, but rather the combined effects of both thyroid autoantibodies or the entire AITD pathology. Therefore, studies evaluating the effects of TgAb individually were needed to understand the role of TgAb in cancer prognosis.
Several studies were conducted on the prognostic effects of TgAb on thyroid cancer in perioperative settings (Table 2). Durante et al. [32] showed that there were more cases of persistent/recurrent disease in thyroid cancer patients with TgAb than in those without TgAb, although these data were not preoperative; instead, TgAb values were obtained 1 to 12 months after thyroidectomy. On the other hand, a study based on a nationwide multicenter registry of thyroid cancer in the United States showed no significant association of TgAb with the stage of disease, disease-free survival, or overall survival [33]. Although these studies found contradictory results, it is interesting to see the potential role of TgAb in the prognosis of thyroid cancer and in its underlying mechanisms.
Since then, there have been several studies reporting a correlation between TgAb and lymph node metastasis in DTC. Vasileiadis et al. [20] reported that DTC patients with TgAb showed more frequent lymph node metastasis than those without TgAb (20.3% vs. 10.0%). Another study also found that elevated preoperative serum TgAb levels in DTC patients were significantly associated with adverse primary tumor characteristics, including nonencapsulated tumors, lymphatic invasion, and lymph node metastasis [34]. Similarly, Zhang et al. [35] found that DTC patients with TgAb had a significantly higher rate of metastasis of cervical lymph nodes, and that lymph node stage was the only independent indicator for persistent TgAb (OR, 3.183). Qin et al. [23] also reported that patients with TgAb showed a higher rate of extrathyroid invasion (30.4% vs. 17.1%, p = 0.031).
One small study by Li et al. [36] evaluated the protein expression of specific invasion-related genes (BRAF V600E and nuclear factor κB [NF-κB]) in thyroid cancer tissues to test whether TgAb is associated with the expression of these genes. The protein expression levels of BRAFV600E and NF-κB were greater in TgAb-positive patients compared to TgAb-negative patients, and a multivariate analysis found that TgAb was an independent factor for predicting lymph node metastasis in thyroid cancer. However, the small number of subjects and the lack of a mechanism for the observed patterns make this result difficult to interpret.
If metastasis or invasion develops from a primary tumor, cancer cells are confined within the site and will induce a cancer-specific immune response, which may in turn cause TgAb levels to rise [37,38]. One recent study used genomic profiling of thyroid cancer to reveal that somatic mutations of Tg derived from metastatic lesions might play a significant role in the pathogenesis of PTC and development of metastasis [39]. Newly developed Tg mutations in this study were associated with a poor prognosis, and we presume these new Tg mutations would induce TgAb. Unfortunately, TgAb was not measured in this study.

POSTOPERATIVE TgAb FOLLOW-UP

High TgAb levels could cause Tg levels to be undetectable. Because of this, follow-up measurements of TgAb levels are useful for detecting persistent or recurrent disease after total thyroidectomy and RI remnant ablation of DTC [4]. Therefore, rising TgAb levels after initial treatment are evaluated as a ‘biochemical incomplete response,’ and these patients should be carefully monitored to detect recurrent or persistent disease [4].
TgAb levels may transiently rise postoperatively as an apparent immune reaction to released tissue particles after surgery, and they may rise after RI [40]. After total thyroidectomy and RI, all antibodies disappeared progressively, with a median disappearance time for TgAb of about 3 years [40,41]. Although the pathophysiologic importance of TgAb after total thyroidectomy is unclear, the persistence of TgAb or increasing titers more than 1 year after thyroidectomy and RI probably indicates the presence of residual thyroid tissue, and possibly an increased risk of recurrence [14]. Furthermore, sequential changes in TgAb titers are a reliable predictor of disease prognosis and therefore serve as a useful factor for clinical decision-making [42]. In a study of thyroid cancer patients with undetectable serum Tg concentrations, 18% of patients with serum TgAb concentrations > 100 U/mL had a recurrence, compared with only 1% of patients with serum TgAb ≤ 100 U/mL [43].
We previously reported that in DTC patients who previously had total thyroidectomy and high-dose RI remnant ablation, thyroid bed RI uptake at the postoperative 6- to 12-month whole-body scan showed a close association with higher TgAb levels, compared to no thyroid bed uptake [44]. Dewi et al. [45] also reported that higher post-RI TgAb levels were significantly correlated with unsuccessful RI therapy (OR, 5.379; p = 0.007), which indicates that TgAb could serve as a surrogate marker for successful RI. We assume that the existence of TgAb represents remnant thyroid tissue, because TgAb can be detected as a response to remaining Tg.
A study by Trimboli et al. [46] evaluated the prognostic impact of pre-RI TgAb levels on long-term outcomes for TgAb-positive DTC patients. Positive TgAb levels before RI increased the risk of disease recurrence over time (OR, 3.57), and disease-free survival was higher in TgAb-negative patients (hazard ratio, 2.59).

FNA WASHOUT TG AND SERUM TgAb LEVELS

FNAC of suspicious lymph nodes in DTC patients frequently shows false-negative results due to easily missed cancer cells in cases with an insufficient number of metastatic cancer cells within the lymph nodes. Therefore, measuring Tg levels in FNA washout (FNA-Tg), in addition to FNAC, has been the best supplementary diagnostic tool to increase the diagnostic accuracy of FNAC [47]. Increased serum TgAb levels could lower serum Tg concentrations, so measurements of Tg should always be accompanied by TgAb testing, as indicated by clinical management guidelines [4]. This leads to the question of whether increased serum TgAb levels could interfere with FNA-Tg levels in metastatic lymph nodes of DTC patients.
Several studies found that the presence of serum TgAb could lower FNA-Tg levels, and therefore measuring serum TgAb levels may be helpful in DTC patients who are bound to FNAC with FNA-Tg on suspicious lymph nodes [48-51]. One study demonstrated that when applying the same FNA-Tg cutoff used in the TgAb-negative group to the TgAb-positive group to detect metastatic lymph nodes in DTC patients, the sensitivity and positive predictive value of FNA-Tg were reduced by more than 10% [51]. A similar result was obtained in a postoperative setting: the TgAb-positive group showed significantly lower FNA-Tg levels than the TgAb-negative group in metastatic lymph nodes, and thus showed lower sensitivity and negative predictive values with the same FNA-Tg levels [49].
In multiple studies, however, high serum TgAb levels showed no interference with FNA-Tg sensitivity [52,53]. Duval et al. [54] reported that the measurement of FNA-Tg is useful for evaluating suspicious lymph nodes in patients with DTC, regardless of TgAb. Boi et al. [53] measured TgAb levels in FNA washout fluid in a limited number of patients, and found that TgAb was undetectable in patients with negative serum TgAb, but a small number of patients with positive serum TgAb (two of eight) showed positive TgAb in washout fluid. FNA-Tg levels from metastatic lymph nodes were lower than those found in TgAb-negative FNA washout fluids, but this difference might not be significant in the diagnostic process. One explanation for why FNA-Tg levels are much higher than TgAb levels in FNA washout fluid is that it may overcome interference by TgAb, due to high Tg levels in metastatic lymph nodes leading to saturated TgAb-binding sites. Thus, the measurement of serum TgAb at the time of FNA-Tg is not recommended in current clinical management guidelines [4]. Additional studies are needed to confirm the interfering effects of serum TgAb levels on FNA washout Tg levels.

CONCLUSIONS

It remains challenging to interpret the diagnostic and prognostic implications of TgAb levels before surgery for DTC patients with TgAb, although basic and clinical researchers have uncovered secret messages from this antibody over the last two decades. Future research should focus on understanding the epitope-specific immunological responses of TgAb in thyroid cancer, as several studies have suggested unique immunological roles for TgAb.

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Table 1.
Odds ratio of predicting thyroid cancer in multiple studies according to preoperative TgAb
Study No. Patients OR (CI)a p value Prediction target Prevalence of positive TgAb, %b p value Prevalence of PTC according to TgAb status, %c p value
Kim et al. (2010) [17] 1,638 FNAC 1.61 (1.12–2.33) 0.010 Suspicious cytologye 19.6 vs. 30.8 < 0.001 16.5 vs. 26.4 0.001
Lun et al. (2013) [26] 3,085 Thyroidectomy 1.89 (1.47-2.44) < 0.001 PTC 20.4 vs. 40.0 < 0.001 28.1 vs. 43.1 < 0.001
Wu et al. (2014) [27] 2,132 Thyroidectomy 1.921 (1.43-2.58) 0.000 PTC 10.4 vs. 16.2 0.000 23.9 vs. 34.4 0.000
Vasileiadis et al. (2014) [20] 854 Thyroidectomy 1.86 (1.21–2.53)d 0.003 PTC 20.8 vs. 32.9 < 0.001 42.4 vs. 57.9 < 0.001
Castagna et al. (2014) [28] 2,504 FNAC NA NA Suspicious cytology 13.0 vs. 10.7 0.57 5.5 vs. 4.5 NA
Grani et al. (2015) [21] 3,777 FNAC 1.74 (1.05–2.88)d 0.03 Suspicious cytology 12.2 vs. 24.0 0.043 4.1 vs. 6.7 < 0.07
Hadjisavva et al. (2015) [29] 322 FNAC NA NA Suspicious cytology 32.6 vs. 36.7 NA 12.2 vs. 16.1 < 0.05
Qin et al. (2015) [23] 1,638 Thyroidectomy 2.10 (1.40–3.15) < 0.001 PTC and FTC 12.6 vs. 23.6 < 0.001 12.9 vs. 24.0 < 0.01
Hosseini et al. (2016) [22] 586 Thyroidectomy 1.86 (1.01-3.41) NA PTC and FTC 9.3 vs. 16.4 0.024 50.4 vs. 65.4 0.05
Selek et al. (2017) [30] 870 Thyroidectomy NA NA PTC 14.0 vs. 17.0 0.31 64.8 vs. 70.5 NA

TgAb, thyroglobulin antibody; OR, odds ratio; CI, confidence interval; PTC, papillary thyroid carcinoma; FNAC, fine needle aspiration cytology; NA, not available; FTC, follicular thyroid cancer.

a OR of predicting thyroid cancer (95% CI).

b Benign vs. suspicious or malignant.

c TgAb negative vs. positive.

d Univariate analysis.

e Suspicious cytology: FNAC including suspicious for malignancy/malignant.

Table 2.
Associations between preoperative TgAb and initial clinical characteristics and prognosis of thyroid cancer
Study No. Age Sex TSH Tumor size Thyroiditis on histology Lymph node metastasis Extrathyroid extension Distant metastasis Recurrence
Vasileiadis et al. (2014) [20] 854 NS NS NA NA NA NA
Durante et al. (2014) [32] 1,240 NS NS NA NA NS NS
Qin et al. (2015) [23] 1,638 NS M < F NA NA NS NA NA
Li et al. (2017) [36] 122 NS NS NA NS
Jo et al. (2017) [34] 1,171 NS M < F NS NS NS NS
Zhang et al. (2017) [35] 98 NS NS NA NA NA NA NA NA

TgAb, thyroglobulin antibody; TSH, thyroid-stimulating hormone; NS, not significant; NA, not available.

REFERENCES

1. Hegedus L. Clinical practice: the thyroid nodule. N Engl J Med 2004;351:1764–1771.
crossref pmid
2. Hori M, Katanoda K. Morphological distribution of thyroid cancer from Cancer Incidence in Five Continents Vol. X. Jpn J Clin Oncol 2015;45:1182.
crossref pmid pdf
3. Cho BY, Choi HS, Park YJ, et al. Changes in the clinicopathological characteristics and outcomes of thyroid cancer in Korea over the past four decades. Thyroid 2013;23:797–804.
crossref pmid pmc
4. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1–133.
crossref pmid pmc
5. Bayer MF, Kriss JP. Immunoradiometric assay for serum thyroglobulin: semiquantitative measurement of thyroglobulin in antithyroglobulin-positive sera. J Clin Endocrinol Metab 1979;49:557–564.
crossref pmid pdf
6. Schneider AB, Pervos R. Radioimmunoassay of human thyroglobulin: effect of antithyroglobulin autoantibodies. J Clin Endocrinol Metab 1978;47:126–137.
crossref pmid pdf
7. Fröhlich E, Wahl R. Thyroid autoimmunity: role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol 2017;8:521.
crossref pmid pmc
8. Roitt IM, Doniach D, Campbell PN, Hudson RV. Auto-antibodies in Hashimoto's disease (lymphadenoid goitre). Lancet 1956;271:820–821.
crossref pmid
9. Rose NR, Witebsky E. Studies on organ specificity. V. Changes in the thyroid glands of rabbits following active immunization with rabbit thyroid extracts. J Immunol 1956;76:417–427.
pmid
10. Barin JG, Talor MV, Sharma RB, Rose NR, Burek CL. Iodination of murine thyroglobulin enhances autoimmune reactivity in the NOD.H2 mouse. Clin Exp Immunol 2005;142:251–259.
crossref pmid pmc
11. Li Y, Teng D, Shan Z, et al. Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 2008;93:1751–1757.
crossref pmid pdf
12. Latrofa F, Ricci D, Grasso L, et al. Characterization of thyroglobulin epitopes in patients with autoimmune and non-autoimmune thyroid diseases using recombinant human monoclonal thyroglobulin autoantibodies. J Clin Endocrinol Metab 2008;93:591–596.
crossref pmid pdf
13. Caturegli P, Kuppers RC, Mariotti S, et al. IgG subclass distribution of thyroglobulin antibodies in patients with thyroid disease. Clin Exp Immunol 1994;98:464–469.
crossref pmid pmc
14. Spencer CA, Takeuchi M, Kazarosyan M, et al. Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 1998;83:1121–1127.
crossref pmid
15. Feldt-Rasmussen U, Rasmussen AK. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems. Hormones (Athens) 2010;9:109–117.
crossref pmid
16. Kebebew E, Treseler PA, Ituarte PH, Clark OH. Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited. World J Surg 2001;25:632–637.
crossref pmid
17. Kim ES, Lim DJ, Baek KH, et al. Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 2010;20:885–891.
crossref pmid
18. Braverman LE, David DS, Werner SC, Ingbar SH. Werner & Ingbar’s the Thyroid: A Fundamental and Clinical Text. Philadelphia (PA): Lippincott Williams & Wilkins, 2013.

19. McLachlan SM, Rapoport B. Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies? Thyroid 2004;14:510–520.
crossref pmid
20. Vasileiadis I, Boutzios G, Charitoudis G, Koukoulioti E, Karatzas T. Thyroglobulin antibodies could be a potential predictive marker for papillary thyroid carcinoma. Ann Surg Oncol 2014;21:2725–2732.
crossref pmid
21. Grani G, Calvanese A, Carbotta G, et al. Thyroid autoimmunity and risk of malignancy in thyroid nodules submitted to fine-needle aspiration cytology. Head Neck 2015;37:260–264.
crossref pmid
22. Hosseini S, Payne RJ, Zawawi F, et al. Can preoperative thyroglobulin antibody levels be used as a marker for well differentiated thyroid cancer? J Otolaryngol Head Neck Surg 2016;45:31.
crossref pmid pmc
23. Qin J, Yu Z, Guan H, Shi L, et al. High thyroglobulin antibody levels increase the risk of differentiated thyroid carcinoma. Dis Markers 2015;2015:648670.
crossref pmid pmc pdf
24. Anil C, Goksel S, Gursoy A. Hashimoto's thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study. Thyroid 2010;20:601–606.
crossref pmid
25. Rago T, Di Coscio G, Ugolini C, et al. Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy. Clin Endocrinol (Oxf ) 2007;67:363–369.
crossref pmid
26. Lun Y, Wu X, Xia Q, et al. Hashimoto's thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis. Otolaryngol Head Neck Surg 2013;148:396–402.
crossref pmid
27. Wu X, Lun Y, Jiang H, et al. Coexistence of thyroglobulin antibodies and thyroid peroxidase antibodies correlates with elevated thyroid-stimulating hormone level and advanced tumor stage of papillary thyroid cancer. Endocrine 2014;46:554–560.
crossref pmid
28. Castagna MG, Belardini V, Memmo S, et al. Nodules in autoimmune thyroiditis are associated with increased risk of thyroid cancer in surgical series but not in cytological series: evidence for selection bias. J Clin Endocrinol Metab 2014;99:3193–3198.
crossref pmid pdf
29. Hadjisavva IS, Dina R, Talias MA, Economides PA. Prevalence of cancer in patients with thyroid nodules in the island of cyprus: predictive value of ultrasound features and thyroid autoimmune status. Eur Thyroid J 2015;4:123–128.
crossref pmid pmc
30. Selek A, Cetinarslan B, Tarkun I, Canturk Z, Ustuner B, Akyay Z. Thyroid autoimmunity: is really associated with papillary thyroid carcinoma? Eur Arch Otorhinolaryngol 2017;274:1677–1681.
crossref pmid pdf
31. Kim EY, Kim WG, Kim WB, et al. Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2009;71:581–586.
crossref pmid
32. Durante C, Tognini S, Montesano T, et al. Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies. Thyroid 2014;24:1139–1145.
crossref pmid pmc
33. McLeod DS, Cooper DS, Ladenson PW, et al. Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis. Thyroid 2014;24:35–42.
crossref pmid pmc
34. Jo K, Kim MH, Ha J, et al. Prognostic value of preoperative anti-thyroglobulin antibody in differentiated thyroid cancer. Clin Endocrinol (Oxf) 2017;87:292–299.
crossref pmid
35. Zhang T, Song LP, Zhao T, Gao W, Lin YS. Effect of lymph node metastasis on change of positive thyroglobulin antibody in differentiated thyroid carcinoma after initial treatment. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2017;39:539–543.
pmid
36. Li W, Ming H, Sun D, et al. The relationship between BRAFV600E, NF-κB and TgAb expression in papillary thyroid carcinoma. Pathol Res Pract 2017;213:183–188.
crossref pmid
37. Nishikawa M, Otsuki T, Ota A, et al. Induction of tumorspecific immune response by gene transfer of Hsp70-cell-penetrating peptide fusion protein to tumors in mice. Mol Ther 2010;18:421–8.
crossref pmid pmc
38. Boon T, Gajewski TF, Coulie PG. From defined human tumor antigens to effective immunization? Immunol Today 1995;16:334–6.
crossref pmid
39. Siraj AK, Masoodi T, Bu R, et al. Genomic profiling of thyroid cancer reveals a role for thyroglobulin in metastasis. Am J Hum Genet 2016;98:1170–1180.
crossref pmid pmc
40. Gorges R, Maniecki M, Jentzen W, et al. Development and clinical impact of thyroglobulin antibodies in patients with differentiated thyroid carcinoma during the first 3 years after thyroidectomy. Eur J Endocrinol 2005;153:49–55.
crossref pmid
41. Chiovato L, Latrofa F, Braverman LE, et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann Intern Med 2003;139(5 Pt 1):346–351.
crossref pmid
42. Hsieh CJ, Wang PW. Sequential changes of serum antithyroglobulin antibody levels are a good predictor of disease activity in thyroglobulin-negative patients with papillary thyroid carcinoma. Thyroid 2014;24:488–493.
crossref pmid
43. Kim WG, Yoon JH, Kim WB, et al. Change of serum antithyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 2008;93:4683–4689.
crossref pmid pdf
44. Lim DJ, O JH, Kim MH, et al. Clinical significance of observation without repeated radioiodine therapy in differentiated thyroid carcinoma patients with positive surveillance whole-body scans and negative thyroglobulin. Korean J Intern Med 2010;25:408–414.
crossref pmid pmc
45. Dewi AR, Darmawan B, Kartamihadja AH, Hidayat B, Masjhur JS. Antithyroglobulin antibody as a marker of successful ablation therapy in differentiated thyroid cancer. World J Nucl Med 2017;16:15–20.
crossref pmid pmc
46. Trimboli P, Zilioli V, Imperiali M, Giovanella L. Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome. Clin Chem Lab Med 2017;55:1995–2001.
crossref pmid pdf
47. Snozek CL, Chambers EP, Reading CC, et al. Serum thyroglobulin, high-resolution ultrasound, and lymph node thyroglobulin in diagnosis of differentiated thyroid carcinoma nodal metastases. J Clin Endocrinol Metab 2007;92:4278–81.
crossref pmid pdf
48. Shin HJ, Lee HS, Kim EK, Moon HJ, Lee JH, Kwak JY. A study on serum antithyroglobulin antibodies interference in thyroglobulin measurement in fine-needle aspiration for diagnosing lymph node metastasis in postoperative patients. PLoS One 2015;10:e0131096.
crossref pmid pmc
49. Jeon MJ, Park JW, Han JM, et al. Serum antithyroglobulin antibodies interfere with thyroglobulin detection in fine-needle aspirates of metastatic neck nodes in papillary thyroid carcinoma. J Clin Endocrinol Metab 2013;98:153–160.
crossref pmid
50. Fiore E, Giustarini E, Mammoli C, et al. Favorable predictive value of thyroid autoimmunity in high aggressive breast cancer. J Endocrinol Invest 2007;30:734–738.
crossref pmid
51. Jo K, Kim MH, Lim Y, et al. Lowered cutoff of lymph node fine-needle aspiration thyroglobulin in thyroid cancer patients with serum anti-thyroglobulin antibody. Eur J Endocrinol 2015;173:489–497.
crossref pmid
52. Baskin HJ. Detection of recurrent papillary thyroid carcinoma by thyroglobulin assessment in the needle washout after fine-needle aspiration of suspicious lymph nodes. Thyroid 2004;14:959–963.
crossref pmid
53. Boi F, Baghino G, Atzeni F, Lai ML, Faa G, Mariotti S. The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies. J Clin Endocrinol Metab 2006;91:1364–1369.
crossref pmid
54. Duval M, Zanella AB, Cristo AP, Faccin CS, Graudenz MS, Maia AL. Impact of serum tsh and anti-thyroglobulin antibody levels on lymph node fine-needle aspiration thyroglobulin measurements in differentiated thyroid cancer patients. Eur Thyroid J 2017;6:292–297.
crossref pmid pmc
Editorial Office
101-2501, Lotte Castle President, 109 Mapo-daero, Mapo-gu, Seoul 04146, Korea
Tel: +82-2-2271-6792   Fax: +82-2-790-0993    E-mail: kaim@kams.or.kr
Copyright © 2018 The Korean Association of Internal Medicine. All rights reserved.
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
powerd by m2community