Dual Role of AITD in TgAb-Positive PTC: Delayed Antibody Clearance with Enhanced RAIT Response

Dual Role of AITD in TgAb-Positive PTC: Delayed Antibody Clearance with Enhanced RAIT Response | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Dual Role of AITD in TgAb-Positive PTC: Delayed Antibody Clearance with Enhanced RAIT Response Hua Ge, Shuting Chen, Linlin Song, Zhiyi Lin, Yuxuan Li, Wenxin Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7359604/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and Objective Elevated thyroglobulin antibody (TgAb) levels in postoperative management of papillary thyroid carcinoma (PTC) are often attributed to tumor recurrence, while the potential impact of autoimmune thyroid disease (AITD) is overlooked. This study aims to clarify the comprehensive effects of AITD on baseline TgAb levels, antibody normalization kinetics, tumor recurrence/metastasis risk, and therapeutic efficacy of radioactive iodine (RAI) therapy (RAIT) in PTC patients. Methods A retrospective cohort of 287 TgAb-positive ( ≥115 IU/mL) PTC patients who underwent total thyroidectomy and received RAIT with ≥6 months follow-up was enrolled. Based on postoperative pathology and thyroid peroxidase antibody (TPOAb) status, patients were divided into Group A0 (non-AITD, n = 70) and Group A1 (AITD-concurrent, n = 217). Clinicopathological characteristics, RAIT response, and TgAb normalization were compared. Results 75.6% (217/287) of the TgAb-positive PTC patients had concurrent AITD. Group A1 exhibited higher pre-RAIT TgAb levels (680.7 ± 320.6 vs. 480.2 ± 280.5 IU/mL, p = 0.023) and recurrence/metastasis rates (38.7% vs. 25.7%, p = 0.048) than Group A0. No significant differences existed in gender, age, primary tumor size, extrathyroidal extension, multifocality, number of lymph node metastases, Lymph node metastasis rate, extranodal extension, or TNM stage (all p > 0.05). Group A1 required fewer cycles of RAI than Group A0 ( p = 0.042), though total RAI dose given and final therapeutic response showed no statistical difference (all p > 0.05). The median TgAb normalization time was significantly longer in Group A1 (40.81 months vs. 33.55 months, Log-rank p = 0.043), with Cox regression confirming slower normalization in A1 (HR=0.667, 95% CI: 0.452–0.983). Conclusion Elevated postoperative serum TgAb levels in PTC patients are frequently associated with concurrent AITD, which correlates with higher TgAb levels and increased recurrence/metastasis risk but does not compromise RAIT efficacy. This highlights the dual role of AITD in PTC prognosis: delaying antibody clearance while enhancing treatment responsiveness. ​​Papillary thyroid carcinoma Thyroglobulin antibody Autoimmune thyroid disease Radioactive iodine therapy Prognosis Figures Figure 1 Figure 2 Introduction​​ Differentiated thyroid carcinoma (DTC) constitutes approximately 90% of all thyroid malignancies, with papillary thyroid carcinoma (PTC) being the most prevalent subtype. Prognostic assessment of PTC remains a critical focus in oncology research [ 1 ]. Thyroglobulin (Tg), a thyroid-specific glycoprotein, is widely recognized as the gold-standard tumor marker for postoperative diagnosis and monitoring of disease recurrence or metastasis in DTC [ 2 ]. However, the presence of thyroglobulin antibody (TgAb) compromises the accuracy of Tg measurements, limiting its clinical utility during follow-up. TgAb also serves as a key biomarker in autoimmune thyroid disease (AITD). Elevated serum TgAb levels are frequently observed in PTC patients following radioactive iodine (RAI) therapy (RAIT). Notably, a significant cognitive gap persists in clinical practice: physicians predominantly attribute elevated TgAb to tumor recurrence or metastasis, while systemic screening for concurrent AITD is often neglected. AITD arises from pathological activation of the immune system against the thyroid, involving complex interactions among genetic, epigenetic, and environmental factors [ 3 ]. Its hallmark features include lymphocytic infiltration and autoantibody production, primarily TgAb and thyroid peroxidase antibody (TPOAb), encompassing Graves' disease (GD) and Hashimoto's thyroiditis (HT). The role of inflammation and immunity in cancer progression is increasingly recognized. Epidemiologic studies report that approximately 23% (range: 5–85%) of PTC patients have concurrent HT [ 4 ], with this proportion exceeding 50% in TgAb-positive cohorts [ 1 ]. Although AITD is linked to PTC pathogenesis, its prognostic implications remain contentious [ 1 , 5 , 6 ], particularly regarding RAIT outcomes in postoperative PTC patients. This retrospective study analyzed 287 TgAb-positive PTC patients stratified by AITD status (defined by histopathological confirmation or positive TPOAb ). We aimed to compare baseline TgAb levels and antibody normalization kinetics between AITD-concurrent and non-AITD groups, evaluate the impact of AITD on tumor recurrence/metastasis risk and investigate whether AITD modifies RAIT treatment response. By integrating these dimensions, this study seeks to elucidate the dynamic characteristics of serum TgAb and prognostic significance of concurrent AITD in PTC patients, providing evidence for risk stratification and personalized management strategies. ​Materials and Methods Study Design and Ethical Compliance This retrospective analysis was performed on 2,795 PTC patients who underwent RAIT between January 2012 and September 2023. The protocol was approved by the Institutional Ethics Committee (Approval No.: K2023-09-002) in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants. Patient Selection and Grouping The inclusion criteria were: 1) patients underwent total thyroidectomy with histopathologically confirmed PTC; 2) received initial RAIT (ablation or adjuvant therapy) at our institution department; 3) had pre-RAIT TgAb ≥115 IU/mL; 4) completed ≥6 months of follow-up with serial serum tests (Tg, TgAb, TPOAb) and imaging studies. The exclusion criteria were: 1) postoperative pathology revealed PTC mixed with other thyroid malignancies and 2) concurrent non-thyroidal malignancies or severe systemic diseases. Patients were stratified by AITD status into two groups: Group A0 (non-AITD)—absence of histopathological AITD features and serum TPOAb negtive (n=70, 24.4%); Group A1 (concurrent AITD)—defined as either 1) histopathologically confirmed Hashimoto’s thyroiditis (HT) or Graves’ disease (GD) (n=142), or 2) elevated serum TPOAb (n=75), totaling 217 patients (75.6%). The patient screening workflow is illustrated in Fig. 1. Data Collection and Definitions Clinicopathological parameters were extracted from electronic medical records, including demographics (gender, age), tumor characteristics ( primary tumor size, extrathyroidal extension, multifocality), nodal status (number of lymph node metastases, lymph node metastasis rate, extranodal extension), and TNM staging (AJCC 8th edition [7]). RAIT parameters encompassed total RAI dose given (GBq) and cycles of RAI. Clinical responses were categorised into four categories: excellent response (ER), indeterminate reponse (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR) [2]. TgAb seroconversion was defined as a transition from positive to persistent negative status (negative threshold: <115 IU/mL).clinical responses were categorised into excellent, indeterminate, biochemical incomplete and structural incomplete. Assessment Methods Serum TgAb, TPOAb, and Tg levels were quantified via electrochemiluminescence immunoassay (Roche Cobas 6000 analyzer). The measurement range for TgAb was 10-4000 IU/mL. Due to the heterogeneity of autoantibodies, which could lead to non-linear sparse phenomena, samples exceeding the upper limit of detection were not diluted. For this study, TgAb levels ≥4000 IU/mL were recorded as 4000 IU/mL. Recurrence/metastasis required concordant positive findings on ≥2 imaging modalities: neck ultrasound, chest CT, ¹³¹I whole-body scan( 131 I-WBS), or ¹⁸F-FDG PET/CT (if indicated), with histopathological confirmation when feasible. Statistical Analysis Continuous variables were reported as mean±SD (independent t-test) or median[IQR] (Mann-Whitney Utest), while categorical variables were presented as frequencies (%) (χ²/Fisher’s exact test). TgAb seroconversion time after RAIT were analyzed using Kaplan-Meier curves with Log-rank testing, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Statistical significance was set at P<0.05 (SPSS 26.0, IBM Corp.). Results Cohort Characteristics and Baseline Findings The final cohort comprised 287 TgAb-positive PTC patients (male: 51, 17.8%; female: 236, 82.2%) with a mean age of 41.7±13.0 years. Concurrent AITD was identified in 75.6% (217/287) of patients (Group A1), while 24.4% (70/287) were classified as non-AITD (Group A0). Group A1 exhibited significantly higher pre-RAIT TgAb levels(680.7±320.6 vs. 480.2±280.5 IU/mL, p = 0.023) and recurrence/metastasis rates (38.7% vs. 25.7%, p = 0.048) compared to Group A0. Notably, no significant differences existed in gender, age, primary tumor size, extrathyroidal extension, multifocality, number of lymph node metastases, lymph node metastasis rate, extranodal extension, or TNM stage (all p > 0.05) (Table 1), indicating comparable baseline tumor pathology despite divergent immune status. Table 1 Comparative Analysis of Baseline Characteristics Parameters Group A0 （ n=70 ） Group A1 （ n=217 ） Statistic p -value Gender, n(%) χ² = 1.640 0.200 Male 16 (22.9) 35 (16.1) Female 54 (77.1) 182 (83.9) Age, years(mean ± SD) 43.5 ± 11.4 41.1 ± 13.4 t = 1.336 0.173 Primary tumor size, cm[M(Q1-Q3)] 1.4 (1.1-2.7) 1.5 (1-2) Z = -0.223 0.823 Extrathyroidal extension, n(%) X 2 = 1.112 0.292 Yes 25 (35.3) 63 (29.1) No 45 (64.7) 154 (70.9) Multifocality, n(%) X 2 = 0.221 0.638 Yes 28 (39.6) 80 (36.7) No 42 (60.4) 137 (63.3) Number of lymph node metastases, n[M(Q1-Q3)] 5 (3-16) 6 (2-19) Z = -0.82 0.412 Lymph node metastasis rate, %[M(Q1-Q3)] 20.0（6.76-40.0） 29.57（14.96-38.61） Z = -0.397 0.692 Extranodal extension, n(%) X 2 = 0.495 0.331 Yes 4 (5.7) 8 (3.9) No 66 (94.3) 209 (96.1) TNM stage, n(%) χ² = 0.002 0.967 Stage I 55 (78.6) 171 (78.8) Stage II-IV 15 (21.4) 46 (21.2) Pre- RAIT TgAb levels, IU/mL(mean±SD) 480.2 ± 280.5 680.7 ± 320.6 t = 2.58 0.023 Pre-RAIT recurrence/metastasis, n(%) χ² = 3.902 0.048 Yes 18 (25.7) 84 (38.7) No 52 (74.3) 133 (61.3) RAIT indicates radioactive iodine therapy, TgAb indicates thyroglobulin antibody, p < 0.05 was considered statistically significant Therapeutic response and Antibody Kinetics As shown in Table 2, Group A1 required fewer cycles of RAI than Group A0I (median: 1 [IQR:1-2] vs. 2 [IQR:1-2], p = 0.042) , though total RAI dose given were comparable (median: 7.4 vs. 3.7 GBq, p = 0.101). Final treatment response distribution showed no statistical difference ( p = 0.235), with excellent response (ER) rates of 38.3% (A1) versus 33.9% (A0). Table 2 Comparative Analysis of RAIT Efficacy and TgAb Kinetics Parameters Group A0 （ n=70 ） Group A1 （ n=217 ） Statistic p -value Total RAI dose given, GBq[M(Q1-Q3)] 3.7 (3.7-7.4) 7.4 (3.7-7.4) Z = -1.638 0.101 Cycles of RAI, n[M(Q1-Q3)] 2（1-2） 1（1-2） Z = -2.032 0.042 Therapeutic response, n( % ) X 2 = 4.306 0.235 ER 24 (33.9) 72 (38.3) IDR 26 (37.3) 45 (23.9) BIR 9 (13.1) 30 (16.0) SIR 11 (15.7) 41 (21.8) TgAb seroconversion status, n( % ) X 2 = 1.604 0.205 seroconverted 27 (39.0) 105 (48.4) not seroconverted 43 (61.0) 112 (51.6) RAI indicates radioactive iodine, ER indicates excellent response, IDR indicates biochemical incomplete response, BIR indicates biochemical incomplete response, SIR indicates structural incomplete response, p < 0.05 was considered statistically significant A pivotal finding emerged in antibody dynamics: Although ultimate TgAb normalization rates were similar (48.4% vs. 39.0%, p = 0.205), Group A1 demonstrated significantly prolonged TgAb seroconversion time (median: 40.81 vs. 33.55 months, Log-rank p = 0.043). Cox regression confirmed slower clearance in concurrent AITD patients (HR=0.667, 95% CI: 0.452–0.983), visually substantiated by Kaplan-Meier curves in Fig. 2. Discussion​ In this study, approximately 75.6% of TgAb-positive PTC patients were found to have concurrent AITD, a proportion slightly higher than previously reported [1]. This discrepancy may be attributed to differences in diagnostic criteria for AITD across studies. While prior research primarily relied on postoperative pathological diagnosis to define AITD [1,4], our study incorporated both serological markers and histopathological confirmation. An alternative explanation involves potential variations in disease incidence across different geographical regions and time periods [8]. This high prevalence serves as a critical reminder to clinicians: During postoperative follow-up of PTC patients receiving RAIT, elevated TgAb levels should not be automatically attributed to tumor recurrence or metastasis. Instead, a "tumor-centric" mindset must be overcome through systematic screening—including TPOAb testing and pathological review—to accurately determine the source of antibodies and achieve comprehensive disease assessment. TgAb is a specific autoantibody induced by Tg released from thyroid cancer cells or residual thyroid tissue [9]. Theoretically, following total thyroidectomy and RAIT, TgAb should progressively decline to undetectable levels as thyroid follicular cells—the source of Tg antigen—are eradicated. Contrary to this expectation, our data revealed significantly prolonged TgAb seroconversion time in patients with concurrent AITD (median: 40.81 vs. 33.55 months, Log-rank p =0.043). This persistent antibody elevation suggests sustained immune activation beyond tumor elimination. Two mechanistic pathways may underlie this phenomenon: 1)Chronic Antigen Stimulation. Residual thyroid tissue (including microscopic cancerous foci or metastatic lesions) may continuously release Tg antigen, perpetuating B-cell activation and antibody production [5]. 2)Expanded Immunological Memory. AITD-associated enlargement of autoreactive lymphocyte pools could prolong antibody generation cycles [4]. Critically, persistent TgAb positivity correlates with higher risks of structural disease persistence or recurrence [10,11]. Consequently, for PTC patients with concurrent AITD, monitoring TgAb dynamics—particularly seroconversion time—holds significant prognostic value, necessitating extended surveillance periods. Notably during baseline pre-RAIT assessment, patients with concurrent AITD exhibited significantly higher recurrence/metastasis rates than non-AITD counterparts (38.7% vs. 25.7%, P=0.048)—a finding consistent with Lubin et al. [12] and Zeng et al. [13]. This observation appears paradoxical when contrasted with prior reports suggesting more indolent tumor biology in AITD-associated PTC (e.g., younger age, smaller tumors, earlier TNM stages) [4,14]. Two interconnected factors likely resolve this discrepancy: First, the superior diagnostic sensitivity of 131 I-WBS SPECT/CT fusion imaging employed in this study—integrating functional metabolic data with anatomical localization—significantly enhanced detection of micronodular metastases (particularly subcentimeter lymph node involvement) compared to conventional ultrasound or chest CT [2,15], thereby more accurately quantifying true disease burden. Second, the dual nature of the AITD immune microenvironment : While lymphocytic infiltration in AITD (especially HT) may restrict primary tumor growth through cytotoxic T-cell and NK cell-mediated antitumor immunity [4,16,17], chronic inflammation concurrently promotes invasiveness and metastatic potential by inducing reactive lymph node hyperplasia, increasing multifocality, extranodal extension, and nodal metastasis incidence [13,18,19]. Notably, despite exhibiting higher pre-RAIT recurrence/metastasis rates, patients with concurrent AITD demonstrated no statistically significant difference in final RAIT response compared to the non-AITD group and required fewer cycles of RAI. This suggests that concurrent AITD does not negatively impact the ultimate prognosis of RAIT and may even indicate favorable treatment responsiveness. This result aligns with the conclusions of Lau et al. [6], who observed favorable responses to RAIT in such patients. Similarly, Chen et al. [20] demonstrated that HT correlates with better disease-free survival rates and lower recurrence risk post-RAIT. Potential mechanisms underlying this phenomenon include: 1) enhanced antigen presentation: AITD-associated hyperactive immunity may boost tumor antigen (e.g., Tg) presentation, improving immune recognition of RAIT-released antigens [5,6]; 2) immune cell synergism: Lymphocytes (cytotoxic T cells, lymphokine-activated killer cells, and natural killer cells) infiltrating HT lesions may directly or indirectly (via cytokine secretion, such as IL-1) target residual tumor cells [5,16]; 3) Antibody-Dependent Cellular Cytotoxicity effect: Elevated anti-thyroid antibodies (TgAb, TPOAb) could enhance antibody-dependent cytotoxicity, collaborating with immune cells to eliminate antigen-expressing tumors [21]; and (4) proactive management: Clinicians may have adopted more aggressive strategies (e.g., thorough lymph node dissection) or stricter follow-up (e.g., lower TSH targets) for AITD patients, contributing to favorable outcomes. Collectively, the dual role of AITD in PTC necessitates that treatment plans account for AITD status to select the most effective therapeutic strategies [22]. Limitations This study is a single-center retrospective investigation, its results may be susceptible to selection bias, and future validation through multicenter prospective large-scale cohort studies is warranted. The analysis primarily relies on postoperative data, lacking detailed preoperative information such as the duration of AITD in patients. Although histopathology remains the gold standard for AITD diagnosis and serum TPOAb has well-established diagnostic value, the accuracy of histopathological diagnosis may be influenced by observer variability, diagnostic focus, and patient-specific factors including disease stage and treatment status. Therefore, future research should adopt more standardized and unified diagnostic criteria and conduct long-term prospective follow-up to address these limitations. Conclusion In summary, this study reveals that concurrent AITD—present in approximately 75.6% of TgAb-positive PTC patients—correlates with elevated initial recurrence/metastasis risk and prolonged TgAb persistence , yet does not impede favorable ultimate responses to RAIT, challenging simplistic views of AITD as a uniformly adverse prognostic factor. Declarations Author Contribution All authors contributed to the study conception and design. Material preparation were performed by LLS and YXL, data collection and data analysis were performed by HG and STC,The first draft of the manuscript was written by HG. ZYL has made significant contributions to the manuscript revised, particularly in terms of data re-collection and manuscript polishing. Manuscript polishing and revision were performed by WXC, ZYL and HG. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Jia X, Pang P, Wang L, Zhao L, Jiang L, Song Y, et al. 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Association between Hashimoto thyroiditis and clinical outcomes of papillary thyroid carcinoma: A meta-analysis. PLoS One. 17(6):e0269995 (2022). DOI: 10.1371/journal.pone.0269995. Yao S, Zhang H. Papillary thyroid carcinoma with Hashimoto's thyroiditis: impact and correlation. Front Endocrinol (Lausanne). 16:1512417 (2025). doi: 10.3389/fendo.2025.1512417. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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10:18:00","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":77971,"visible":true,"origin":"","legend":"","description":"","filename":"e9e309ba491640b1a79baeef6dab1e931structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7359604/v1/d0184dc911590c794041042d.xml"},{"id":92584260,"identity":"2809ffe8-6cab-4bb3-970d-018e3f2e796b","added_by":"auto","created_at":"2025-10-01 10:10:00","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":87090,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7359604/v1/2ac02397fa05f5519bc420ea.html"},{"id":92584250,"identity":"38a3e8df-948b-465c-bd75-eef3f277410b","added_by":"auto","created_at":"2025-10-01 10:10:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53995,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDiagram of the data collection process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePTC indicates papillary thyroid carcinoma , TgAb indicates thyroglobulin antibody, AITD indicates autoimmune thyroid disease\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7359604/v1/32cfe366e455bf8e7cb990aa.png"},{"id":92584251,"identity":"ba159067-a195-494d-bbaf-19c824d2d08c","added_by":"auto","created_at":"2025-10-01 10:10:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49122,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier curve of TgAb seroconversion over time in Group A0 and Group A1\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7359604/v1/08bd74a5d580046560527aa6.png"},{"id":92596191,"identity":"d60b9f85-ac3a-47bd-8aaf-beb34e3ea04a","added_by":"auto","created_at":"2025-10-01 13:17:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":946868,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7359604/v1/3041cc43-9144-427e-8af0-fc92744c8708.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Dual Role of AITD in TgAb-Positive PTC: Delayed Antibody Clearance with Enhanced RAIT Response","fulltext":[{"header":"Introduction​​","content":"\u003cp\u003eDifferentiated thyroid carcinoma (DTC) constitutes approximately 90% of all thyroid malignancies, with papillary thyroid carcinoma (PTC) being the most prevalent subtype. Prognostic assessment of PTC remains a critical focus in oncology research [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Thyroglobulin (Tg), a thyroid-specific glycoprotein, is widely recognized as the gold-standard tumor marker for postoperative diagnosis and monitoring of disease recurrence or metastasis in DTC [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, the presence of thyroglobulin antibody (TgAb) compromises the accuracy of Tg measurements, limiting its clinical utility during follow-up. TgAb also serves as a key biomarker in autoimmune thyroid disease (AITD). Elevated serum TgAb levels are frequently observed in PTC patients following radioactive iodine (RAI) therapy (RAIT). Notably, a significant cognitive gap persists in clinical practice: physicians predominantly attribute elevated TgAb to tumor recurrence or metastasis, while systemic screening for concurrent AITD is often neglected.\u003c/p\u003e\u003cp\u003eAITD arises from pathological activation of the immune system against the thyroid, involving complex interactions among genetic, epigenetic, and environmental factors [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Its hallmark features include lymphocytic infiltration and autoantibody production, primarily TgAb and thyroid peroxidase antibody (TPOAb), encompassing Graves' disease (GD) and Hashimoto's thyroiditis (HT). The role of inflammation and immunity in cancer progression is increasingly recognized. Epidemiologic studies report that approximately 23% (range: 5\u0026ndash;85%) of PTC patients have concurrent HT [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], with this proportion exceeding 50% in TgAb-positive cohorts [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Although AITD is linked to PTC pathogenesis, its prognostic implications remain contentious [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], particularly regarding RAIT outcomes in postoperative PTC patients.\u003c/p\u003e\u003cp\u003eThis retrospective study analyzed 287 TgAb-positive PTC patients stratified by AITD status (defined by histopathological confirmation or positive TPOAb ). We aimed to compare baseline TgAb levels and antibody normalization kinetics between AITD-concurrent and non-AITD groups, evaluate the impact of AITD on tumor recurrence/metastasis risk and investigate whether AITD modifies RAIT treatment response. By integrating these dimensions, this study seeks to elucidate the dynamic characteristics of serum TgAb and prognostic significance of concurrent AITD in PTC patients, providing evidence for risk stratification and personalized management strategies.\u003c/p\u003e"},{"header":"​Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Ethical Compliance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis was performed on 2,795 PTC patients who underwent RAIT between January 2012 and September 2023. The protocol was approved by the Institutional Ethics Committee (Approval No.: K2023-09-002) in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Selection and Grouping\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria were: 1) patients underwent total thyroidectomy with histopathologically confirmed PTC; 2) received initial RAIT (ablation or adjuvant therapy) at our institution department; 3) had pre-RAIT TgAb\u0026nbsp;≥115 IU/mL; 4) completed ≥6 months of follow-up with serial serum tests (Tg, TgAb, TPOAb) and imaging studies. The exclusion criteria were: 1) postoperative pathology revealed PTC mixed with other thyroid malignancies and 2) concurrent non-thyroidal malignancies or severe systemic diseases.\u003c/p\u003e\n\u003cp\u003ePatients were stratified by AITD status into two groups: Group A0 (non-AITD)—absence of histopathological AITD features and serum TPOAb negtive (n=70, 24.4%); Group A1 (concurrent AITD)—defined as either 1) histopathologically confirmed Hashimoto’s thyroiditis (HT) or Graves’ disease (GD) (n=142), or 2) elevated serum TPOAb (n=75), totaling 217 patients (75.6%). The patient screening workflow is illustrated in Fig. 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection and Definitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinicopathological parameters were extracted from electronic medical records, including demographics (gender, age), tumor characteristics ( primary tumor size, extrathyroidal extension, multifocality), nodal status (number of lymph node metastases, lymph node metastasis rate, extranodal extension), and TNM staging (AJCC 8th edition [7]). RAIT parameters encompassed total RAI dose given (GBq) and cycles of RAI. Clinical responses were categorised into four categories: excellent response (ER), indeterminate reponse (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR) [2]. TgAb seroconversion was defined as a transition from positive to persistent negative status (negative threshold: \u0026lt;115 IU/mL).clinical responses were categorised into excellent, indeterminate, biochemical incomplete and structural incomplete.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum TgAb, TPOAb, and Tg levels were quantified via electrochemiluminescence immunoassay (Roche Cobas 6000 analyzer). \u0026nbsp;The measurement range for TgAb was 10-4000 IU/mL. Due to the heterogeneity of autoantibodies, which could lead to non-linear sparse phenomena, samples exceeding the upper limit of detection were not diluted. For this study, TgAb levels\u0026nbsp;≥4000 IU/mL were recorded as 4000 IU/mL. Recurrence/metastasis required concordant positive findings on ≥2 imaging modalities: neck ultrasound, chest CT, ¹³¹I whole-body scan(\u003csup\u003e131\u003c/sup\u003eI-WBS), or ¹⁸F-FDG PET/CT (if indicated), with histopathological confirmation when feasible.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables were reported as mean±SD (independent t-test) or median[IQR] (Mann-Whitney Utest), while categorical variables were presented as frequencies (%) (χ²/Fisher’s exact test). TgAb seroconversion time after RAIT were analyzed using Kaplan-Meier curves with Log-rank testing, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Statistical significance was set at P\u0026lt;0.05 (SPSS 26.0, IBM Corp.).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eCohort Characteristics and Baseline Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe final cohort comprised 287 TgAb-positive PTC patients (male: 51, 17.8%; female: 236, 82.2%) with a mean age of 41.7\u0026plusmn;13.0 years. Concurrent AITD was identified in 75.6% (217/287) of patients (Group A1), while 24.4% (70/287) were classified as non-AITD (Group A0).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGroup A1 exhibited significantly higher pre-RAIT TgAb levels(680.7\u0026plusmn;320.6 vs. 480.2\u0026plusmn;280.5 IU/mL, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.023) \u0026nbsp;and recurrence/metastasis rates (38.7% vs. 25.7%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.048) compared to Group A0. Notably, no significant differences existed in gender, age, primary tumor size, extrathyroidal extension, multifocality, number of lymph node metastases, lymph node metastasis rate, extranodal extension, or TNM stage (all \u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05) (Table 1), indicating comparable baseline tumor pathology despite divergent immune status.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Comparative Analysis of Baseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"625\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A0\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=70\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A1\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=217\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStatistic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 457px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender, n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;\u0026nbsp;\u003c/em\u003e= 1.640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e16 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e35 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e54 (77.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e182 (83.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years(mean\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u003cstrong\u003eSD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e43.5 \u0026plusmn; 11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e41.1 \u0026plusmn; 13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u0026nbsp;\u003c/em\u003e= 1.336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.173\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor size, cm[M(Q1-Q3)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.4 (1.1-2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.5 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eZ = -0.223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 457px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtrathyroidal extension, n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003eX\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/em\u003e= 1.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.292\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e25 (35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e63 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e45 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e154 (70.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultifocality, n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003eX\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/em\u003e= 0.221\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.638\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e28 (39.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e80 (36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e42 (60.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e137 (63.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of lymph node metastases, n[M(Q1-Q3)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e5 (3-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e6 (2-19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eZ = -0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.412\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymph node metastasis rate, %[M(Q1-Q3)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e20.0（6.76-40.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e29.57（14.96-38.61）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eZ = -0.397\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 457px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtranodal extension, n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003eX\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/em\u003e= 0.495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.331\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e4 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e8 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e66 (94.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e209 (96.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 457px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTNM stage, n(%)\u0026nbsp;\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;\u0026nbsp;\u003c/em\u003e= 0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.967\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eStage I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e55 (78.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e171 (78.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eStage II-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e15 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e46 (21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-\u003c/strong\u003e\u003cstrong\u003eRAIT\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTgAb levels, IU/mL(mean\u0026plusmn;SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e480.2 \u0026plusmn; 280.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e680.7 \u0026plusmn; 320.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u0026nbsp;\u003c/em\u003e= 2.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 457px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-RAIT recurrence/metastasis, n(%)\u0026nbsp;\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;\u0026nbsp;\u003c/em\u003e= 3.902\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e18 (25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e84 (38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 243px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e52 (74.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e133 (61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRAIT indicates radioactive iodine therapy, TgAb indicates thyroglobulin antibody, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTherapeutic response and Antibody Kinetics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 2, Group A1 required fewer cycles of RAI than Group A0I (median: 1 [IQR:1-2] vs. 2 [IQR:1-2], \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.042) , though total RAI dose given were comparable (median: 7.4 vs. 3.7 GBq, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.101). Final treatment response distribution showed no statistical difference (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.235), with excellent response (ER) rates of 38.3% (A1) versus 33.9% (A0).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Comparative Analysis of RAIT Efficacy and TgAb Kinetics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"625\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A0\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=70\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A1\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=217\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStatistic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal RAI dose given, GBq[M(Q1-Q3)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e3.7 (3.7-7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e7.4 (3.7-7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u0026nbsp;\u003c/em\u003e= -1.638\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCycles of RAI, n[M(Q1-Q3)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e2（1-2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e1（1-2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eZ = -2.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.042\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 469px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapeutic response,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003en(\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cem\u003eX\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e= 4.306\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.235\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e24 (33.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e72 (38.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003eIDR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e26 (37.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e45 (23.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003eBIR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e9 (13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e30 (16.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; SIR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e11 (15.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e41 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 469px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTgAb seroconversion status,\u003c/strong\u003e\u003cstrong\u003en(\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cem\u003eX\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e= 1.604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003eseroconverted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e27 (39.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e105 (48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 222px;\"\u003e\n \u003cp\u003enot seroconverted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e43 (61.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e112 (51.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRAI indicates radioactive iodine, ER indicates excellent response, IDR indicates biochemical incomplete response, BIR indicates biochemical incomplete response, SIR indicates structural incomplete response, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/p\u003e\n\u003cp\u003eA pivotal finding emerged in antibody dynamics: Although ultimate TgAb normalization rates were similar (48.4% vs. 39.0%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.205), Group A1 demonstrated significantly prolonged TgAb seroconversion time (median: 40.81 vs. 33.55 months, Log-rank \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.043). Cox regression confirmed slower clearance in concurrent AITD patients (HR=0.667, 95% CI: 0.452\u0026ndash;0.983), visually substantiated by Kaplan-Meier curves in Fig. 2.\u003c/p\u003e"},{"header":"Discussion​","content":"\u003cp\u003eIn this study, approximately 75.6% of TgAb-positive PTC patients were found to have concurrent AITD, a proportion slightly higher than previously reported [1]. This discrepancy may be attributed to differences in diagnostic criteria for AITD across studies. While prior research primarily relied on postoperative pathological diagnosis to define AITD [1,4], our study incorporated both serological markers and histopathological confirmation. An alternative explanation involves potential variations in disease incidence across different geographical regions and time periods [8]. This high prevalence serves as a critical reminder to clinicians: During postoperative follow-up of PTC patients receiving RAIT, elevated TgAb levels should not be automatically attributed to tumor recurrence or metastasis. Instead, a \"tumor-centric\" mindset must be overcome through systematic screening—including TPOAb testing and pathological review—to accurately determine the source of antibodies and achieve comprehensive disease assessment.\u003c/p\u003e\n\u003cp\u003eTgAb is a specific autoantibody induced by Tg released from thyroid cancer cells or residual thyroid tissue [9]. Theoretically, following total thyroidectomy and RAIT, TgAb should progressively decline to undetectable levels as thyroid follicular cells—the source of Tg antigen—are eradicated. Contrary to this expectation, our data revealed significantly prolonged TgAb seroconversion time in patients with concurrent AITD (median: 40.81 vs. 33.55 months, Log-rank \u003cem\u003ep\u003c/em\u003e=0.043). This persistent antibody elevation suggests sustained immune activation beyond tumor elimination. Two mechanistic pathways may underlie this phenomenon: 1)Chronic Antigen Stimulation. Residual thyroid tissue (including microscopic cancerous foci or metastatic lesions) may continuously release Tg antigen, perpetuating B-cell activation and antibody production [5]. 2)Expanded Immunological Memory. AITD-associated enlargement of autoreactive lymphocyte pools could prolong antibody generation cycles [4]. Critically, persistent TgAb positivity correlates with higher risks of structural disease persistence or recurrence [10,11]. Consequently, for PTC patients with concurrent AITD, monitoring TgAb dynamics—particularly seroconversion time—holds significant prognostic value, necessitating extended surveillance periods.\u003c/p\u003e\n\u003cp\u003eNotably during baseline pre-RAIT assessment, patients with concurrent AITD exhibited significantly higher recurrence/metastasis rates than non-AITD counterparts (38.7% vs. 25.7%, P=0.048)—a finding consistent with Lubin et al. [12] and Zeng et al. [13]. This observation appears paradoxical when contrasted with prior reports suggesting more indolent tumor biology in AITD-associated PTC (e.g., younger age, smaller tumors, earlier TNM stages) [4,14]. \u0026nbsp;Two interconnected factors likely resolve this discrepancy: First, the \u0026nbsp;superior diagnostic sensitivity of \u003csup\u003e131\u003c/sup\u003eI-WBS SPECT/CT fusion imaging employed in this study—integrating functional metabolic data with anatomical localization—significantly enhanced detection of micronodular metastases (particularly subcentimeter lymph node involvement) compared to conventional ultrasound or chest CT [2,15], thereby more accurately quantifying true disease burden. Second, the dual nature of the AITD immune microenvironment : While lymphocytic infiltration in AITD (especially HT) may restrict primary tumor growth through cytotoxic T-cell and NK cell-mediated antitumor immunity [4,16,17], chronic inflammation concurrently promotes invasiveness and metastatic potential by inducing reactive lymph node hyperplasia, increasing multifocality, extranodal extension, and nodal metastasis incidence [13,18,19].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNotably, despite exhibiting higher pre-RAIT recurrence/metastasis rates, patients with concurrent AITD demonstrated no statistically significant difference in final RAIT response compared to the non-AITD group and required fewer cycles of RAI. This suggests that concurrent AITD does not negatively impact the ultimate prognosis of RAIT and may even indicate favorable treatment responsiveness. This result aligns with the conclusions of Lau et al. [6], who observed favorable responses to RAIT in such patients. Similarly, Chen et al. [20] demonstrated that HT correlates with better disease-free survival rates and lower recurrence risk post-RAIT.\u003c/p\u003e\n\u003cp\u003ePotential mechanisms underlying this phenomenon include: 1) enhanced antigen presentation: AITD-associated hyperactive immunity may boost tumor antigen (e.g., Tg) presentation, improving immune recognition of RAIT-released antigens [5,6]; 2) immune cell synergism: Lymphocytes (cytotoxic T cells, lymphokine-activated killer cells, and natural killer cells) infiltrating HT lesions may directly or indirectly (via cytokine secretion, such as IL-1) target residual tumor cells [5,16]; 3) Antibody-Dependent Cellular Cytotoxicity effect: Elevated anti-thyroid antibodies (TgAb, TPOAb) could enhance antibody-dependent cytotoxicity, collaborating with immune cells to eliminate antigen-expressing tumors [21]; and (4) proactive management: Clinicians may have adopted more aggressive strategies (e.g., thorough lymph node dissection) or stricter follow-up (e.g., lower TSH targets) for AITD patients, contributing to favorable outcomes. Collectively, the dual role of AITD in PTC necessitates that treatment plans account for AITD status to select the most effective therapeutic strategies [22].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a single-center retrospective investigation, its results may be susceptible to selection bias, and future validation through multicenter prospective large-scale cohort studies is warranted. The analysis primarily relies on postoperative data, lacking detailed preoperative information such as the duration of AITD in patients. Although histopathology remains the gold standard for AITD diagnosis and serum TPOAb has well-established diagnostic value, the accuracy of histopathological diagnosis may be influenced by observer variability, diagnostic focus, and patient-specific factors including disease stage and treatment status. Therefore, future research should adopt more standardized and unified diagnostic criteria and conduct long-term prospective follow-up to address these limitations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this study reveals that concurrent AITD—present in approximately 75.6% of TgAb-positive PTC patients—correlates with elevated initial recurrence/metastasis risk and prolonged TgAb persistence , yet does not impede favorable ultimate responses to RAIT, challenging simplistic views of AITD as a uniformly adverse prognostic factor.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation were performed by LLS and YXL, data collection and data analysis were performed by HG and STC,The first draft of the manuscript was written by HG. ZYL has made significant contributions to the manuscript revised, particularly in terms of data re-collection and manuscript polishing. Manuscript polishing and revision were performed by WXC, ZYL and HG. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJia X, Pang P, Wang L, Zhao L, Jiang L, Song Y, et al. Clinical Analysis of Preoperative Anti-thyroglobulin Antibody in Papillary Thyroid Cancer Between 2011 and 2015 in Beijing, China: A Retrospective Study[J]. Front Endocrinol (Lausanne). 11:452 (2020). doi: 10.3389/fendo.2020.00452. \u003c/li\u003e\n\u003cli\u003eNuclear Medicine Association of Chinese Medical Association. \u003csup\u003e131\u003c/sup\u003eI guidelines of the treatment of differentiated thyroid cancinoma (2021 edition). \u003cem\u003eChin J Nucl Med Mol Imaging.\u003c/em\u003e 41(4): 218-41 (2021). doi:10.3760/cma.j.cn321828-20201113-00412.\u003c/li\u003e\n\u003cli\u003eVargas-Uricoechea H. Autoimmune Thyroid Disease and Differentiated Thyroid Carcinoma: A Review of the Mechanisms That Explain an Intriguing and Exciting Relationship. World J Oncol. 15(1):14-27 (2024). doi: 10.14740/wjon1728. \u003c/li\u003e\n\u003cli\u003eXue X, Wu D, Yao H, Wang K, Liu Z, Qu H. Mechanisms underlying the promotion of papillary thyroid carcinoma occurrence and progression by Hashimoto\u0026apos;s thyroiditis. Front Endocrinol (Lausanne). 31;16:1551271 (2025). doi: 10.3389/fendo.2025.1551271. \u003c/li\u003e\n\u003cli\u003eFerrari SM, Fallahi P, Elia G, Ragusa F, Ruffilli I, Paparo SR, et al. Thyroid autoimmune disorders and cancer. Semin Cancer Biol. 64:135-146 (2020). doi: 10.1016/j.semcancer.2019.05.019. \u003c/li\u003e\n\u003cli\u003eLau J, Lee J, Mahipal M, Yang SP, Tan WB, Yuan NK, et al. Hashimoto\u0026apos;s thyroiditis on outcomes in papillary thyroid cancer revisited: experience from South East Asia. Ann R Coll Surg Engl. 104(6):465-471 (2022). doi: 10.1308/rcsann.2021.0224.\u003c/li\u003e\n\u003cli\u003eAmin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. New York: Springer. 3-30 (2017).\u003c/li\u003e\n\u003cli\u003eIeni A, Vita R, Magliolo E, Santarpia M, Di Bari F, Benvenga S, et al. One-third of an Archivial Series of Papillary Thyroid Cancer (Years 2007-2015) Has Coexistent Chronic Lymphocytic Thyroiditis, Which Is Associated with a More Favorable Tumor-Node-Metastasis Staging. Front Endocrinol (Lausanne). 8:337 (2017). doi: 10.3389/fendo.2017.00337. \u003c/li\u003e\n\u003cli\u003eSanjari M, Ordooei M, Amirkhosravi L, Naghibzadeh-Tahami A, Nazemi S. The effect of positive thyroglobulin antibodies on the prognosis and treatment response in patients with papillary thyroid carcinoma. Heliyon. 10(4):e26092 (2024). doi: 10.1016/j.heliyon.2024.e26092. \u003c/li\u003e\n\u003cli\u003eGe H, Chen W, Lin Z, Li Y, Chen S. Analysis of the prognostic value of thyroglobulin antibody change trends during follow-up after 131I treatment in patients with differentiated thyroid carcinoma. Front Oncol. 15:1496594 (2025). doi: 10.3389/fonc.2025.1496594. \u003c/li\u003e\n\u003cli\u003eWu K, Shi L, Wang J, Xie L. Association between papillary thyroid carcinoma and lymphocytic thyroiditis: A retrospective study. Oncol Lett. 25(4):148 (2023). doi: 10.3892/ol.2023.13734. \u003c/li\u003e\n\u003cli\u003ePalella M, Giustolisi FM, Modica Fiascaro A, Fichera M, Palmieri A, Cannarella R,et al. Risk and Prognosis of Thyroid Cancer in Patients with Graves\u0026apos; Disease: An Umbrella Review. Cancers (Basel). 15(10):2724 (2023). doi: 10.3390/cancers15102724. \u003c/li\u003e\n\u003cli\u003eZeng B, Min Y, Feng Y, Xiang K, Chen H, Lin Z. Hashimoto\u0026apos;s Thyroiditis Is Associated With Central Lymph Node Metastasis in Classical Papillary Thyroid Cancer: Analysis from a High-Volume Single-Center Experience. Front Endocrinol (Lausanne). 13:868606 (2022). doi: 10.3389/fendo.2022.868606. \u003c/li\u003e\n\u003cli\u003eOsborne D, Choudhary R, Vyas A, Kampa P, Abbas LF, Chigurupati HD, et al. Hashimoto\u0026apos;s Thyroiditis Effects on Papillary Thyroid Carcinoma Outcomes: A Systematic Review. Cureus. 14(8):e28054 (2022). doi: 10.7759/cureus.28054. \u003c/li\u003e\n\u003cli\u003eIssa PP, Omar M, Buti Y, Aboueisha M, Munshi R, Hussein M, et al. Hashimoto\u0026apos;s Thyroiditis: A Protective Factor against Recurrence in BRAF-Wild Type Differentiated Thyroid Carcinoma. Cancers (Basel). 15(8):2371 (2023). doi: 10.3390/cancers15082371.\u003c/li\u003e\n\u003cli\u003eMin Y, Wang X, Chen H, Yin G. The exploration of Hashimoto\u0026apos;s Thyroiditis related miscarriage for better treatment modalities. Int J Med Sci. 17(16):2402-2415 (2020). doi: 10.7150/ijms.48128.\u003c/li\u003e\n\u003cli\u003eLee I, Kim HK, Soh EY, Lee J. The Association Between Chronic Lymphocytic Thyroiditis and the Progress of Papillary Thyroid Cancer. World J Surg. 44(5):1506-1513 (2020). doi: 10.1007/s00268-019-05337-9. \u003c/li\u003e\n\u003cli\u003eCappellacci F, Canu GL, Lai ML, Lori E, Biancu M, Boi F, et al. Association between hashimoto thyroiditis and differentiated thyroid cancer: A single-center experience. Front Oncol. 12:959595 (2022) . doi: 10.3389/fonc.2022.959595.\u003c/li\u003e\n\u003cli\u003ePremoli P, Tanda ML, Piantanida E, Veronesi G, Gallo D, Masiello E, et al. Features and outcome of differentiated thyroid carcinoma associated with Graves\u0026apos; disease: results of a large, retrospective, multicenter study. J Endocrinol Invest. 43(1):109-116 (2020). doi: 10.1007/s40618-019-01088-5.\u003c/li\u003e\n\u003cli\u003eChen XY, Tan Y, Wang D, Wei ZX. Radioactive iodine therapy for thyroid cancer coexisting with Hashimoto\u0026apos;s thyroiditis: a systematic review and meta-analysis. Br J Radiol. 97(1160):1423-1430 (2024). doi: 10.1093/bjr/tqae118. \u003c/li\u003e\n\u003cli\u003eTang Q, Pan W, Peng L. Association between Hashimoto thyroiditis and clinical outcomes of papillary thyroid carcinoma: A meta-analysis. PLoS One. 17(6):e0269995 (2022). DOI: 10.1371/journal.pone.0269995. \u003c/li\u003e\n\u003cli\u003eYao S, Zhang H. Papillary thyroid carcinoma with Hashimoto\u0026apos;s thyroiditis: impact and correlation. Front Endocrinol (Lausanne). 16:1512417 (2025). doi: 10.3389/fendo.2025.1512417. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"​​Papillary thyroid carcinoma, Thyroglobulin antibody, Autoimmune thyroid disease, Radioactive iodine therapy, Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-7359604/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7359604/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Objective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eElevated thyroglobulin antibody (TgAb) levels in postoperative management of papillary thyroid carcinoma (PTC) are often attributed to tumor recurrence, while the potential impact of autoimmune thyroid disease (AITD) is overlooked. This study aims to clarify the comprehensive effects of AITD on baseline TgAb levels, antibody normalization kinetics, tumor recurrence/metastasis risk, and therapeutic efficacy of radioactive iodine (RAI) therapy (RAIT) in PTC patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective cohort of 287 TgAb-positive ( ≥115 IU/mL) PTC patients who underwent total thyroidectomy and received RAIT with ≥6 months follow-up was enrolled. Based on postoperative pathology and thyroid peroxidase antibody (TPOAb) status, patients were divided into Group A0 (non-AITD, n = 70) and Group A1 (AITD-concurrent, n = 217). Clinicopathological characteristics, RAIT response, and TgAb normalization were compared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e75.6% (217/287) of the TgAb-positive PTC patients had concurrent AITD. Group A1 exhibited higher pre-RAIT TgAb levels (680.7 ± 320.6 vs. 480.2 ± 280.5 IU/mL, \u003cem\u003ep \u003c/em\u003e= 0.023) and recurrence/metastasis rates (38.7% vs. 25.7%, \u003cem\u003ep \u003c/em\u003e= 0.048) than Group A0. No significant differences existed in gender, age, primary tumor size, extrathyroidal extension, multifocality, number of lymph node metastases, Lymph node metastasis rate, extranodal extension, or TNM stage (all \u003cem\u003ep \u003c/em\u003e\u0026gt; 0.05). Group A1 required fewer cycles of RAI than Group A0 ( \u003cem\u003ep \u003c/em\u003e= 0.042), though total RAI dose given and final therapeutic response showed no statistical difference (all \u003cem\u003ep \u003c/em\u003e\u0026gt; 0.05). The median TgAb normalization time was significantly longer in Group A1 (40.81 months vs. 33.55 months, Log-rank \u003cem\u003ep \u003c/em\u003e= 0.043), with Cox regression confirming slower normalization in A1 (HR=0.667, 95% CI: 0.452–0.983).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eElevated postoperative serum TgAb levels in PTC patients are frequently associated with concurrent AITD, which correlates with higher TgAb levels and increased recurrence/metastasis risk but does not compromise RAIT efficacy. This highlights the dual role of AITD in PTC prognosis: delaying antibody clearance while enhancing treatment responsiveness.\u003c/p\u003e","manuscriptTitle":"Dual Role of AITD in TgAb-Positive PTC: Delayed Antibody Clearance with Enhanced RAIT Response","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-01 10:09:55","doi":"10.21203/rs.3.rs-7359604/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2c077606-8c01-421d-80b8-f691bf93f22f","owner":[],"postedDate":"October 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-01T13:08:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-01 10:09:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7359604","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7359604","identity":"rs-7359604","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}