Coexisting medullary and papillary thyroid cancer (MTC–PTC) are rare, and large-scale studies with sufficient sample sizes to delineate its distinct characteristics remain limited. This study included 87 patients pathologically diagnosed with MTC–PTC. For comparison, two additional cohorts consisting of 709 patients with solitary MTC and 1,178 patients with solitary PTC were included. Biological features and survival outcomes were systematically evaluated across patients. Compared with solitary MTC, the MTC–PTC cohort had significantly lower preoperative calcitonin, fewer RET mutations and earlier tumor stages in MTC components (all P < 0.05). MTC–PTC cases were further divided into ipsilateral and contralateral groups according to their spatial locations. Compared with both the contralateral and solitary MTC groups, the ipsilateral group consisted exclusively of sporadic MTCs and demonstrated the lowest frequency of RETM918T mutations, the highest proportion of T1-stage tumors, and the lowest calcitonin levels (all P < 0.05). Multivariable Cox regression also identified the ipsilateral group as an independent predictor of improved structural recurrence–free survival (P < 0.001). PTC lesions in contralateral group exhibited less aggressive features than ipsilateral and solitary PTCs, including lower rates of extrathyroidal extension and multifocality (P = 0.007), lower TGAb levels (P = 0.021), earlier T/N stages. This study highlights distinct clinicopathological and survival differences between coexisting and solitary thyroid cancers, as well as between subtypes of MTC–PTC. Further studies with larger cohorts and integrative molecular analyses are warranted to elucidate these mechanisms.

Advanced differentiated thyroid cancer (DTC) is characterized by limited therapeutic options and unfavorable prognosis. To address this, we conduct proteogenomic analysis of 113 advanced DTCs, identifying three molecularly distinct subtypes: canonical, stromal, and immunogenic. These subtypes exhibit differences in driver mutations, histopathological features, and clinical outcomes. Based on their unique biology, we suggest distinct therapeutic strategies for each subtype. To facilitate clinical application, we develop a machine learning classifier that accurately predicts these subtypes using routinely available gene mutation and digital pathology data. The biological relevance of this classification is further confirmed in an independent cohort analyzed by single-cell and spatial transcriptomics. Moreover, analysis of a real-world cohort of patients receiving various systemic therapies provides preliminary clinical evidence supporting the potential utility of this subtyping framework for informing treatment decisions. Collectively, this study provides a rationale and a practical tool for future exploration of personalized treatment in advanced DTC.

Background Radical resection for locally advanced differentiated thyroid cancer (DTC) is challenging and associated with significant morbidity. This study aimed to evaluate the efficacy and safety of neoadjuvant apatinib (a multikinase inhibitor) and camrelizumab (a PD-1 inhibitor) in this setting. Methods This was a single-center, single-arm, phase 2 trial. Eligible patients with locally advanced, unresectable or borderline-resectable DTC received neoadjuvant apatinib (250 mg daily) and camrelizumab (200 mg every two weeks) until surgery, disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included R0/R1 resection rate, disease control rate (DCR), and safety. Results Six patients were enrolled before the trial was terminated early due to the COVID-19 pandemic. Among five evaluable patients, the ORR was 60% (95% CI: 23.1%-88.2%), and the DCR was 100% (95% CI: 56.6%-100.0%). All five patients underwent subsequent surgery with an R0/R1 resection rate of 100%, which facilitated preservation of involved critical structures in most cases. Treatment-related adverse events were primarily grade 1–2. No grade 4/5 events occurred. At a median follow-up of 36.4 months, no disease progression or death was observed. Pathological analysis revealed heterogeneous treatment-induced morphological changes and PD-L1 Tumor Proportion Score (TPS) dynamics based on treatment response. Conclusion Neoadjuvant apatinib plus camrelizumab demonstrated promising antitumor activity and an acceptable safety profile in patients with locally advanced DTC, enabling successful surgical resection with organ preservation in this preliminary cohort. These results warrant further investigation in larger prospective studies. Trial registration ClinicalTrials.gov: NCT04612894 (Registration Date: 2020-10-30)

Accurate preoperative diagnosis of thyroid nodules via fine-needle aspiration (FNA) biopsy remains challenging, particularly in cases with indeterminate cytology. This prospective, noninterventional, blinded, multicenter study establishes ThyroProt, a diagnostic classifier that integrates targeted mass-spectrometry-based quantification of a 3-protein signature with BRAFV600E mutation status, age, and gender. Developed and validated on 837 FNA samples, the classifier is evaluated in a prospective test set of 322 samples, achieving an area under the curve (AUC) of 0.94 with an overall accuracy of 90.7%. For the critical subgroup of Bethesda III/IV nodules, ThyroProt demonstrates an accuracy of 88.0%, with 82.4% sensitivity and 100% specificity. The classifier's robust performance is further evaluated in two independent multicenter cohorts, where it maintains an AUC of 0.87-0.91 and an accuracy of 84.3%-85.7%. This study supports the clinical utility of mass-spectrometry-based targeted proteomics for improving preoperative diagnosis of thyroid nodules, particularly those with indeterminate cytology.

Total thyroidectomy (TT) is the standard surgical approach for hereditary medullary thyroid cancer (hMTC). However, it is not rare in clinical practice for patients with hMTC to initially undergo hemithyroidectomy (HT) because the hereditary nature of the disease is not recognized until after surgery, particularly during early periods when RET testing was not widely available. We identified and assembled a multicenter cohort of patients with hMTC who underwent initial HT to (1) characterize their long-term outcomes and (2) compare prognosis with those receiving TT. This retrospective multicenter study included 152 patients with hMTC from 13 referral centers across China. Biochemical response, structural recurrence-free survival (SRFS), and disease-specific survival (DSS) were compared between the HT and TT groups using Kaplan-Meier survival analysis, Firth’s logistic regression, and Firth’s Cox regression. Among 152 patients with hMTC, 20 (13.2

BACKGROUND: Medullary thyroid cancer (MTC) is a heterogeneous and aggressive malignancy with limited therapeutic options. Metabolic reprogramming, a hallmark of cancer, may offer a promising avenue for understanding and managing MTC. METHODS: RNA sequencing data of 101 MTC samples were obtained from a published dataset PRJCA008783, and untargeted metabolomic profiling was performed on 51 paired samples. Metabolic subtypes were identified using clustering analyses and validated using immunohistochemistry (47 cases), multiplex immunofluorescence (12 cases), and a previously published single-cell RNA sequencing dataset (7 cases derived from PRJCA021386). Deep learning-based approaches were applied to develop prognostic models. RESULTS: Three metabolic subtypes were identified. The M3 subtype, associated with poor prognosis, was characterised by upregulated glycosaminoglycan (GAGs) biosynthesis, particularly chondroitin sulfate, and elevated expression of CHSY1, a key GAGs biosynthetic enzyme. M3 tumours displayed enhanced epithelial-mesenchymal transition (EMT) signatures. Multi-omic analyses implicated CHSY1 may promote EMT through interactions with myofibroblasts, which was supported by immunohistochemistry and immunofluorescence. Two prognostic classifiers, the 8 Metabolites Model and the 28 Metabolic Genes Model, effectively stratified patients by recurrence risk, with predictive power largely driven by GAGs-associated metabolism. CONCLUSIONS: Our study reveals substantial metabolic heterogeneity in MTC and proposes a novel metabolic classification system, offering mechanistic insights and supporting metabolite-driven prognostication for precision management of MTC.

Background:Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are both rare and aggressive thyroid cancers. Advances in targeted therapy and immunotherapy have changed treatment strategies and improved prognosis in these patients. Methods:This single-center cohort study included patients diagnosed with locally advanced or metastatic PDTC/ATC at Fudan University Shanghai Cancer Center (FUSCC) between 2019 and 2023. Patients were either enrolled in clinical trials or received treatment based on clinical guidelines and expert consensus. Gene testing was conducted using next-generation sequencing of clinical samples. Results:95 patients were analyzed (PDTC = 34, ATC = 61). Median overall survival (OS) was 19.7 months for PDTC and 9.5 months for ATC (P = 0.478). Among 82 patients who underwent gene testing, the most frequent gene alterations in PDTC were BRAF (50.0%), TERT promoter (39.3%), and TP53 (25.0%) mutations; in ATC, they were TERT promoter (55.6%), BRAF (42.6%), and TP53 (25.9%) mutations. Compared with ATC patients, PDTC patients were more likely to receive best supportive care and less likely to be enrolled in clinical trials or treated with PD-1 inhibitors. The 1-year OS rates for PDTC/ATC patients receiving neoadjuvant therapy + surgery, systemic treatment, and supportive care only were 83.3, 51.2, and 5.7%, respectively (P < 0.001). After adjusting for covariates, neoadjuvant therapy + surgery (hazard ratio = 0.216, 95% confidence interval: 0.647-0.718, P = 0.012) was an independent predictor of superior OS. Conclusion:Despite the generally poor prognosis, aggressive treatment, particularly neoadjuvant therapy, has been shown to improve survival. Personalized treatment is crucial for optimizing treatment strategies for PDTC/ATC.

BACKGROUND:The current AJCC TNM staging system for medullary thyroid cancer (MTC) is largely adapted from criteria for differentiated thyroid cancer, which may not fully capture MTC-specific prognostic factors. This study aimed to evaluate the prognostic significance of upper mediastinal lymph node metastasis (LNM) and propose corresponding modifications to the N category and staging system to improve their applicability for MTC. METHODS:We conducted a population-based, retrospective study enrolling patients with MTC from 19 Chinese referral centers. Demographics and pathologic characteristics were collected, and patients were categorized into 4 LNM subgroups: no LNM, central cervical LNM, lateral cervical LNM, and upper mediastinal (level VII) LNM. We assessed their prognostic significance using Kaplan-Meier survival curves and Cox regression analysis. Recursive partitioning analysis was then applied to regroup patients with similar overall survival (OS). To validate our findings, we analyzed an independent cohort from the SEER database. RESULTS:Our multicenter cohort included 827 patients with initially treated MTC, of whom 438 (53.0%) were female, with a median age of 50 years (IQR, 40-59). Upper mediastinal (level VII) LNM was present in 12.6% of patients and was significantly associated with worse OS, structural recurrence-free survival, and biochemical response compared with other LNM sites (all P<.05). Based on these findings, we proposed up-classifying level VII metastases from N1a to a new category, N1c, while keeping the T and M definitions unchanged. We then regrouped 4 TNM stages: stage I (T1-2N0-1aM0), stage II (T1-3N1bM0, T3N0-1aM0), stage III (T4N0-1bM0, T1-3N1cM0), and stage IV (T4N1cM0, T1-4N0-1cM1). Our modified staging system demonstrated superior prognostic discrimination and predictive power compared with the current AJCC TNM system, both in our multicenter cohort and the SEER validation cohort. CONCLUSIONS:For the first time, we identified the upper mediastinum as the most critical site for regional LNM in MTC. Our proposed adjustments to the N category and TNM staging system could provide better risk stratification for patients with MTC, potentially guiding improved clinical management and treatment strategies.

Background::Cytopathology cannot be used to reliably distinguish follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), the second most common form of thyroid cancer, because they exhibit nearly identical cellular morphology. Given the challenges in diagnosis and treatment, this study aims to identify the mechanisms underlying FTC.Methods::Using parallel reaction monitoring-mass spectrometry (PRM-MS) assays, we identified and quantified 94 differentially expressed protein candidates from a retrospective cohort of 1085 FTC and FTA tissue samples from 18 clinical centers. Of these targeted proteins, those with the potential for distinguishing FTC from FTA were prioritized using machine learning. Co-immunoprecipitation (co-IP) and immunofluorescence co-localization assays, as well as gene interference, overexpression, and immunohistochemistry (IHC) experiments, were used to investigate the interactions and cellular functions of selected proteins.Results::Using machine learning models and feature selection methods, 30 of the 94 candidates were prioritized as key proteins. Co-IP and immunofluorescence co-localization assays using FTC cell lines revealed interactions among insulin-like growth factor 2 receptor (IGF2R), major vault protein (MVP), histone deacetylase 1 (HDAC1), and histone H1.5 (H1-5). Gene interference and overexpression experiments in FTC-133 cells confirmed the promotional role of these proteins in cell proliferation. IHC assays of patient samples further confirmed elevated expression of these four proteins in FTC compared with that in FTA.Conclusions::Our findings underscore the utility of advanced proteomic techniques in elucidating the molecular underpinnings of FTC, highlighting the potential significance of IGF2R, MVP, HDAC1, and H1-5 in FTC progression, and providing a foundation for the exploration of targeted therapies.

Differentiating follicular thyroid adenoma (FTA) from carcinoma (FTC) remains challenging due to similar histological features separate from invasion. This study developed and validated DNA- and/or protein-based classifiers. A total of 2443 thyroid samples from 1568 patients were obtained from 24 centers in China and Singapore. Next-generation sequencing of a 66-gene panel revealed 41 (62.1%) detectable genes, while 25 were not, showing similar alteration patterns with differing mutation frequencies. Proteomics quantified 10,336 proteins, with 187 dysregulated. A discovery protein-based XGBoost model achieved an AUROC of 0.899 (95% CI, 0.849-0.949), outperforming the gene-based model (AUROC 0.670 [95% CI, 0.612-0.729]). A subsequent 24-protein classifier, developed via targeted mass spectrometry and validated in three independent sets, showed high performance in retrospective cohorts (AUROC 0.871 [95% CI, 0.833-0.910] and 0.853 [95% CI, 0.772-0.934]) and prospective biopsies (AUROC 0.781 [95% CI, 0.563-1.000]). It exhibited a 95.7% negative predictive value for ruling out malignancy. This study presents a promising protein-based approach for the differential diagnosis of FTA and FTC, potentially enhancing diagnostic accuracy and clinical decision-making.

Background: Medullary thyroid cancer (MTC) is a rare thyroid malignancy, with 70% to 80% of cases being sporadic (sMTC). Current guidelines recommend total thyroidectomy (TT) for all preoperatively suspicious sMTC, though there has been increasing support for reducing the surgical extent in recent years. However, relevant data are limited. This study aimed to comprehensively evaluate the safety of hemithyroidectomy (HT) in sMTC. Patients and Methods: This study included 797 patients with MTC who received curative-intent initial surgery at 19 participating referral centers. Genetic testing was performed to identify disease heredity. We evaluated the safety of HT in sMTC across 5 aspects: (1) prevalence of occult bilateral foci, (2) prevalence of contralateral lobe recurrence, (3) biochemical response, (4) structural recurrence-free survival (SRFS), and (5) overall survival (OS). Results: Of the 797 patients, 648 were genetically confirmed as having sMTC. HT and TT were performed as the index surgery in 232 (35.8%) and 416 (64.2%) patients, respectively. In the TT group, bilateral foci were found in 34 (8.2%) patients, of whom only 10 (2.4%) had sonographically occult foci, and of these, only 3 (0.72%) had a maximal tumor size <= 2 cm. In the HT group, only 1.7% (4/232) had recurrence in the preserved lobe, with only 1 (0.43%) having a maximal tumor size <= 2 cm. After propensity score matching, 230 pairs of patients were included in further analysis. No significant differences were found in OS (logrank: P =.484; Cox regression: P=.380), SRFS (log-rank: P =.914; Cox regression: P=.309), or biochemical response (chi-square: P =.744; logistic regression: P =.818) between the 2 groups. Subgroup analyses showed that HT conferred comparable structural and biochemical outcomes with TT in small (<= 2 cm) sMTCs, even for patients with high-risk factors such as high preoperative calcitonin, multifocal disease, lymph node metastases, RET M918T mutation, and desmoplasia. Conclusions: For small unilateral sMTCs, HT may be considered an alternative treatment that does not compromise prognosis while avoiding additional complications associated with TT.

Tumor microenvironment (TME) remodeling plays a pivotal role in thyroid cancer progression, yet its spatial dynamics remain unclear. In this study, we integrate spatial transcriptomics and single-cell RNA sequencing to map the TME architecture across para-tumor thyroid (PT) tissue, papillary thyroid cancer (PTC), locally advanced PTC (LPTC), and anaplastic thyroid carcinoma (ATC). Our integrative analysis reveals extensive molecular and cellular heterogeneity during thyroid cancer progression, enabling the identification of three distinct thyrocyte meta-clusters, including TG+IYG+ subpopulation in PT, HLA-DRB1+HLA-DRA+ subpopulation in early cancerous stages, and APOE+APOC1+ subpopulation in late-stage progression. We reveal stage-specific tumor leading edge remodeling and establish high-confidence cell-cell interactions, such as COL8A1-ITHB1 in PTC, LAMB2-ITGB4 in LPTC, and SERPINE1-PLAUR in ATC. Notably, both SERPINE1 expression level and SERPINE1+ fibroblast abundance correlate with malignant progression and prognosis. These findings provide a spatially resolved framework of TME remodeling, offering insights for thyroid cancer diagnosis and treatment.

Importance:Calcitonin is the most sensitive and specific biomarker for medullary thyroid cancer (MTC). Basal serum calcitonin levels are strongly associated with the burden of lymph node metastasis (LNM) and can help guide the extent of neck dissection. However, the predictive thresholds for varying degrees of LNM are based on laboratory testing methods no longer in use. Objective:To update the optimal thresholds of basal serum calcitonin levels for predicting the extent of LNM. Design, Setting, and Participants:This retrospective cohort study included initially treated patients with MTC who had their preoperative basal calcitonin levels tested using electrochemiluminescence or chemiluminescence from a Chinese multicenter cohort of 13 hospitals between 2011 and 2024. The patients were randomly divided into a training and a validation cohort in a 2:1 ratio. The data were analyzed between June 2024 and September 2024. Exposures:Preoperative basal serum calcitonin using electrochemiluminescence or chemiluminescence. Main Outcomes and Measures:The main outcome is Structural recurrence-free survival (SRFS) based on the group partitioned by the proposed thresholds predicting different LNMs. Results:A total of 509 patients were included in the study with a median (interquartile range [IQR]) follow-up of 52 (27-84) months. The median (IQR) age at diagnosis was 50 (40-59) years, and 279 patients (54.8%) were female individuals. Patients were categorized into 4 groups based on the extent of LNM: no LNM, central LNM, lateral LNM, and upper mediastinal LNM. A positive correlation was found between preoperative calcitonin levels and the extent of LNM (η2 = 0.28). Using the training cohort, preoperative basal calcitonin thresholds associated with different extents of LNM were identified as follows: 241.9 pg/mL for central LNM, 693.9 pg/mL for ipsilateral lateral LNM, 2787.1 pg/mL for upper mediastinal LNM, and 2378.5 pg/mL for bilateral and/or contralateral lateral LNM. In both the training and validation cohorts, the proposed thresholds outperformed those recommended by the American Thyroid Association guidelines not only in the prediction of LNM, but also in the discrimination of SRFS. Conclusions:In this cohort study, updated threshold values of preoperative serum calcitonin predicted different extents of LNM, which may provide optimal cutoffs for future prospective studies on biomarker-guided selective neck dissection in patients with MTC.

Background: Medullary thyroid cancer (MTC) is a rare thyroid malignancy, with 70% to 80% of cases being sporadic (sMTC). Current guidelines recommend total thyroidectomy (TT) for all preoperatively suspicious sMTC, though there has been increasing support for reducing the surgical extent in recent years. However, relevant data are limited. This study aimed to comprehensively evaluate the safety of hemithyroidectomy (HT) in sMTC. Patients and Methods: This study included 797 patients with MTC who received curative-intent initial surgery at 19 participating referral centers. Genetic testing was performed to identify disease heredity. We evaluated the safety of HT in sMTC across 5 aspects: (1) prevalence of occult bilateral foci, (2) prevalence of contralateral lobe recurrence, (3) biochemical response, (4) structural recurrence-free survival (SRFS), and (5) overall survival (OS). Results: Of the 797 patients, 648 were genetically confirmed as having sMTC. HT and TT were performed as the index surgery in 232 (35.8%) and 416 (64.2%) patients, respectively. In the TT group, bilateral foci were found in 34 (8.2%) patients, of whom only 10 (2.4%) had sonographically occult foci, and of these, only 3 (0.72%) had a maximal tumor size ≤2 cm. In the HT group, only 1.7% (4/232) had recurrence in the preserved lobe, with only 1 (0.43%) having a maximal tumor size ≤2 cm. After propensity score matching, 230 pairs of patients were included in further analysis. No significant differences were found in OS (log-rank: P=.484; Cox regression: P=.380), SRFS (log-rank: P=.914; Cox regression: P=.309), or biochemical response (chi-square: P=.744; logistic regression: P=.818) between the 2 groups. Subgroup analyses showed that HT conferred comparable structural and biochemical outcomes with TT in small (≤2 cm) sMTCs, even for patients with high-risk factors such as high preoperative calcitonin, multifocal disease, lymph node metastases, RETM918T mutation, and desmoplasia. Conclusions: For small unilateral sMTCs, HT may be considered an alternative treatment that does not compromise prognosis while avoiding additional complications associated with TT.

Context: Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. Objective: The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. Materials and Methods: Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. Results: A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung, and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (P = .007) and cancer-specific survival (P = .0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality and cancer-specific mortality (all P < .05). When analyzing different metastatic patterns, PTR significantly lowered the risk of overall mortality and cancer-specific mortality for patients with bone, lung, liver, or distant lymph node involvement (all P < .05). Additionally, among patients with 1 or 2 metastases, those undergoing surgical resection were significantly associated with favorable overall survival (P = .008) and cancer-specific survival (P = .0247). Conclusion: PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

Adverse effects during induction chemoimmunotherapy and adjuvant immunotherapy

Recurrence patterns and reasons for death (N=27)

Changes of quality of life at different timepoints

Background:Over 500,000 new cases are diagnosed with papillary thyroid cancer (PTC) globally per year, of whom the vast majority are in the low-risk stratification. Although thyroid-stimulating hormone (TSH) suppression is traditionally recommended for all postoperative PTCs in current guidelines, its necessity remains highly controversial in low-risk patients. Since relevant recommendations in current guidelines are still empirical, we aim to provide a direct, large-scale, real-world evidence. Methods:This large-scale real-world retrospective study included 11,140 low-risk PTC patients from two Chinese large-volume centers (Fudan University Shanghai Cancer Center [FUSCC] and Cancer Hospital of Chinese Academy of Medical Sciences [CH-CAMS]) treated from January 1, 2000 to June 30, 2022. The mean TSH level was calculated based on postoperative serum TSH values during follow-up. The primary outcome was the association between postoperative TSH level and structural recurrence assessed by Kaplan-Meier, log-rank, multivariate Cox regression analyses and equivalence testing by Two One-Sided Tests (TOST) procedure. Propensity score matching (PSM) was used to adjust for confounders among groups. Findings:A total of 11,140 patients with low-risk PTC were included with a median follow-up of 70 months. Based on the mean TSH level, we classified these patients into ≤0.5 (n = 1,504, 13.5%), (0.5-1] (n = 4,336, 38.9%), (1-2] (n = 4,285, 38.5%), (2-3] (n = 704, 6.3%) and >3 (n = 311, 2.8%) mU/L groups. After PSM adjusting for age, sex, T and N stage, 8991 patients were included in further analysis, for whom the log-rank analyses showed no significant differences between any two groups (all P > 0.05) in recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS), and suppressed TSH was not associated with tumor recurrence in the multivariate Cox analysis (TSH > 2 group vs TSH ≤ 2 group: HR = 1.30, 95% CI = 0.85-2.01, P = 0.23). Furthermore, the TOST equivalence tests showed that tumor recurrence status of any two TSH groups were statistically comparable (all Bonferroni-corrected P values < 0.005). Subgroup multivariate analyses showed that TSH level did not impact tumor recurrence regardless of age, tumor size, lymph node metastasis, multifocality, surgical extent, biochemical evidence. Interpretation:Our results suggested that postoperative TSH level was not associated with tumor recurrence in patients with low-risk PTC, for whom deliberate TSH suppression may be exempted to avoid potential secondary complications. Maintaining a TSH level within the normal range may be safe for these patients. Funding:The study was supported by the National Natural Science Foundation of China (82072951 to Y.W.; 82373008 to X.S.), Shanghai Hospital Development Center (SHDC2020CR6003-001 to Y.W., SHDC2024CRI087 to Y.-J.W.), the Science and Technology Commission of Shanghai Municipality (22Y21900100/23DZ2305600 to Y.W.; 23ZR1412000 to X.S.), the Shanghai Anticancer Association Foundation (SACA-AX202213 to Yu Wang), Shanghai Municipal Health Commission and Shanghai Medicine and Health Development Foundation (WJWRC202302 to X.S.).

The Differential Expression of Various Genes between the Resistant and Sensitive Groups