Thyroid最新文献

Background: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are aggressive thyroid cancers with limited treatment options and poor prognosis. While the tumor microenvironment (TME), especially cancer-associated fibroblasts (CAFs), is known to support tumor growth, its metabolic role is not well understood. This study aimed to investigate the role of type 2 deiodinase (D2)-an enzyme converting thyroxine to active triiodothyronine (T3)-in sustaining a pro-tumorigenic TME in PDTC and ATC. Methods: We analyzed D2 expression in both thyroid cancer epithelial cells and CAFs, including inflammatory CAFs (iCAFs), using murine and human PDTC/ATC models. Functional relevance was assessed through pharmacological inhibition of D2 in mouse xenograft models and coculture three-dimensional (3D) spheroids. The effects on tumor growth, CAF composition, and epithelial-stromal signaling were evaluated. In addition, human PDTC-derived organoids were used to test responsiveness to thyroid hormone (TH) modulation. Results: D2 was found to be highly expressed in CAFs, particularly iCAFs, exceeding levels observed in cancer epithelial cells. In vivo inhibition of D2 led to reduced tumor growth and changes in CAF profiles and activation. In 3D coculture spheroids, D2 activity was essential for tumor cell proliferation via a paracrine loop that enhanced local TH signaling. Human PDTC organoids expressing D2 also responded to TH modulation, confirming a positive effect of T3 on tumoral growth in this context. Conclusions: We identified D2 as a key mediator of stromal-epithelial cross talk in PDTC and ATC and highlight local TH metabolism as a potential therapeutic target in these lethal cancers.

Background: Patient-reported scar perception and quality of life (QoL) are critical, yet understudied, outcomes in open thyroid surgery. While the postoperative time is likely to shape patients' recovery trajectories, its relationship with scar perception and QoL remains unknown. Methods: In this cross-sectional study, adult patients with thyroid cancer who underwent open thyroidectomy at Peking Union Medical College Hospital and two affiliated institutions between 2013 and 2024 were stratified by postoperative interval (POI) (≤1, 1-2, 2-3, 3-5, >5 years). Data were collected from electronic medical records. Scar perception (assessed using the Patient Scar Assessment Questionnaire [PSAQ]) and QoL (evaluated using the 39-item Thyroid-Related Patient-Reported Outcome [ThyPRO-39]) were assessed via a blinded web-based questionnaire. Associations between POI and these outcomes were evaluated using linear regression. Mediation analysis was conducted to quantify the effects of POI on QoL via scar perception. Results: Of 1962 eligible patients, 1387 responded (response rate 70.7%), and 1334 patients were included in the final analysis. Scar perception improved progressively with longer POI (β for >5 years vs. ≤1 year, -14.75 [95% confidence intervals [CI], -17.69 to -11.82]), with the most rapid improvement in the total PSAQ scores observed within the first two postoperative years (β for 1-2 years vs. ≤1 year, -6.24 [95% CI, -8.65 to -3.84]). QoL gains followed similar temporal patterns (β for >5 years vs. ≤1 year, -4.79 [95% CI, -6.50 to -3.04], p < 0.001). Secondary analyses showed that obesity and lateral lymph node dissection were significantly associated with the total PSAQ score only in females, but not in males. Mediation analysis indicated that the effect of POI on QoL was fully mediated by scar perception. Conclusions: Post-thyroidectomy scar perception improves dynamically over time and serves as a primary driver of QoL enhancements. This process exhibits sex-specific patterns, highlighting the first two postoperative years as a critical period for scar-related interventions to enhance long-term patient outcomes.

Background: Treatment of patients with thyroid cancer with Na[¹³¹I]I is routinely performed with empirical activity levels. Treatment success may be expected to correlate with the absorbed doses delivered to targets (thyroid remnants or metastatic lesions), but no systematic review or meta-analysis of absorbed dose-effect relationships has yet been performed. Methods: A systematic review and meta-analysis of reports published before August 22, 2025, was performed using PubMed, Web of Science, and OVID MEDLINE. Studies were included if they reported the proportion of patients achieving successful outcome as defined in individual publications and the absorbed doses delivered to targets. The study is registered with PROSPERO (CRD42024554956). Results: In total, 3723 studies were identified of which 18 were eligible for analysis. Number of patients in the included studies ranged from 4 to 509. For patients treated with Na[¹³¹I]I for thyroid remnant ablation, the reported success rates ranged from 60% to 100%, while lower success rates of 43-58% were found for patients with metastatic lesions. Success rates for patients with a thyroid remnant absorbed dose of 300 Gy or more ranged from 78% to 96%, while patients with metastatic lesions receiving at least 80 Gy had success rates ranging from 46% to 98%. Conclusions: While individual studies have demonstrated the importance of absorbed doses from Na[¹³¹I]I for differentiated thyroid cancer, no conclusive absorbed dose-effect relationship has been established in this review. A lack of standardization of dosimetry methodologies and follow-up criteria in the studies obscures the relationship. Large-scale observational prospective studies are required to determine the absorbed doses required for successful personalized treatments of patients with thyroid cancer with Na[¹³¹I]I.

Background: Graves' disease is the leading cause of hyperthyroidism in children and adolescents, with recent studies indicating a rising incidence. Epidemiological data on trends and determinants influencing this rise remain limited. This study aims to assess the trends in incidence of pediatric Graves' disease in the United States and stratify incidence patterns based on patient sex, age, geographic region, urban vs. rural setting, and insurance plan type. Methods: This retrospective cohort study utilized the Merative™ Marketscan® outpatient insurance claims database from 2007 to 2022. Pediatric patients diagnosed with Graves' disease were identified using International Classification of Diseases (ICD)-9 and ICD-10 codes. Annual incidence rates were analyzed over the study period to detect temporal trends. Incidence rates were further stratified by demographic variables including sex, age, geographic region, community setting (urban vs. rural), and insurance plan. Statistical methods included chi-square, ANOVA, and linear regression models to identify significant trends and differences across subgroups. Results: 3377 total new diagnoses of pediatric Graves' disease were identified during the 16-year study period. The average annual incidence rate was 3.33 per 100,000 (SD = 0.33), with an annual increase of 0.042 per 100,000 (p = 0.39). Marked differences in average annual incidence rates were observed across sex and age group; female patients exhibited greater average annual incidence rate (5.04 per 100,000) compared with male patients (1.67 per 100,000). Adolescents, patients 13-17 years of age, had the highest average annual incidence rate (5.72 per 100,000) compared with other age groups. On multivariable regression analysis, female patients had a significant increase in annual incidence by 1.69 cases per 100,000 compared with male patients [CI: 0.82-2.56]. Adolescents also saw a significant increase in adjusted annual incidence by 4.92 cases per 100,000 compared with the other age groups [CI: 3.80-6.04]. No significant change in annual incidence rate was observed across insurance plan, geographic region, or rural status. Conclusions: This study quantifies and delineates trends in pediatric Graves' disease incidence in the United States. The greatest average incidence rate was observed among female and adolescent patients. This study underscores the importance of monitoring Graves' disease trends to facilitate early disease detection and management. Further research is needed to elucidate the genetic and environmental factors underlying these epidemiological trends.

Background: The International Medullary Thyroid Carcinoma Grading System (IMTCGS) is a two-tier score that classifies high-grade medullary thyroid carcinoma (MTC) by the presence of at least one of the following features: mitotic index ≥5/2 mm², Ki-67 proliferation index ≥5%, or tumor necrosis. Cases lacking all three features are classified as low-grade. This study aimed to validate the prognostic role of the IMTCGS in patients with metastatic MTC. The prognostic significance of a high proliferative index (Ki-67 index ≥20%) was also investigated. Methods: We conducted a monocentric retrospective study of 99 metastatic MTC patients treated at Gustave Roussy between 2000 and 2024, in whom the IMTCGS was assessed on the primary tumor. Results: IMTCGS high-grade tumors were found in 67 patients (67.7%), who were older (p = 0.009) and had larger primary tumors (p < 0.001) compared with 32 patients with low-grade tumors. Postoperative calcitonin levels, number of metastatic sites/patient, prevalence of synchronous metastases, and RET-M918T mutation were similar between groups. Median overall survival (OS) was shorter in patients with IMTCGS high-grade than low-grade (4.8 vs. 13.9 years; p = 0.01), as was time to systemic treatment initiation (TTI) (1.0 vs. 4.8 years; p < 0.001). However, among the 75 patients who received systemic therapy, OS from treatment initiation was similar between the two groups (2.8 vs. 3.89 years; p = 0.865). RET-M918T mutation was not associated with worse OS. On multivariable analysis, IMTCGS high-grade and bone metastases were independently associated with both shorter OS and TTI (p < 0.05 for both). Patients with Ki-67 index ≥20% had worse OS (2.6 years) compared with those with Ki-67 index <5% (10.5 years; hazard ratio [HR] = 6.11; p < 0.001) and 5-19% (6.5 years; HR = 3.29; p = 0.001). Conclusions: The IMTCGS is a strong independent prognostic factor in patients with metastatic MTC. Patients with IMTCGS high-grade tumors and Ki-67 index ≥20% represent a high-risk subgroup with the poorest prognosis.

Objectives: The current American Joint Committee on Cancer medullary thyroid cancer (MTC) staging system qualitatively stratifies lymph node (LN) status based on involved LN compartments; however, American Thyroid Association guidelines note that quantitative assessment of LN metastases "should be incorporated." Several studies have proposed LN ratio (LNR) and number of positive LNs as prognostic parameters. We (1) assess whether there are prognostically significant LN thresholds, (2) estimate their association with MTC-specific mortality, and (3) appraise the identified thresholds using an institutional database. Methods: In this retrospective cohort analysis, MTC patients were abstracted from the Surveillance, Epidemiology, and End Results database (2004-20). Cox models with restricted cubic splines assessed the functional relationship of LNR and positive LN count with MTC-specific mortality. Thresholds were estimated using Markov Chain Monte Carlo and bootstrapping. Multivariable models estimated the association of the thresholds with mortality. The testing cohort comprised 149 patients with MTC at a single institution (1996-2025). Results: There were 2709 patients in the derivation cohort; 2098 (77.4%) had LNs examined. Mean patient age was 54.1 years, 59.1% were female, and 69.6% were non-Hispanic White. Mean tumor size was 23.5 mm; 52.7% of patients with LNs examined had ≥1 positive LN. The 5-year MTC-specific survival was 93.3%. Threshold values of 7.8 positive LNs and a LNR of 13.8% were identified (nonlinearity p < 0.001 for both). Adjusted analyses revealed that ≥8 positive LNs were associated with a significantly increased hazard of MTC-specific mortality (hazard ratio [HR] 1.54, confidence interval [CI]: 1.09-2.17, p = 0.014, model area under the curve [AUC] 86.7%); a LNR ≥14% was associated with a significantly increased mortality hazard (HR: 3.308, CI: 2.096-5.222, p < 0.001, model AUC: 87.9%). The thresholds were significantly associated with recurrence-free survival in the testing cohort: 5-year recurrence-free survival was 56.5% (CI: 39.5 - 70.4) for patients with ≥8 positive LNs and 90.5% (CI: 82.5 - 94.9) for <8 (log-rank p < 0.001); it was 67.9% (CI: 55 - 77.9) for patients with LNR ≥14% and 92.8% (CI: 83.6 - 97) for LNR <14 (log-rank p < 0.001). Conclusions: Using population-level data, we identified robust LN thresholds associated with MTC-specific mortality. Compared with a threshold of 8 positive LNs, a LNR threshold ≥14% was associated with a greater increase in hazard of MTC-specific mortality.

Background: The American Thyroid Association has stratified RET C634 mutations as high risk. The association between RET C634R mutation and a more aggressive medullary thyroid carcinoma (MTC) behavior compared with other C634 mutations remains inconclusive, possibly due to the lack of large cohorts and long-term outcome data. This study aimed to evaluate the aggressiveness and long-term outcomes of hereditary MTC in patients with different RET codon 634 mutations. Methods: This study is an international, multicenter, retrospective cohort study. Data from patients with hereditary MTC carrying RET codon 634 mutations treated at three tertiary medical centers were retrospectively analyzed. Clinicopathological features and long-term outcomes were compared between patients with the C634R and those with other C634 mutations (C634F/G/S/W/Y). Results: The study cohort included 317 patients (C634R: 133; C634F/G/S/W/Y: 184) from 137 families with a median follow-up of 10.6 years (4.9-16.6 years). Patients with the C634R mutation were slightly younger at the time of initial surgery (27.8 ± 12.1 vs. 31.3 ± 14.9, p = 0.025). Meanwhile, the C634R group showed larger primary tumors (1.9 ± 1.2 vs. 1.5 ± 1.1, p = 0.006). Kaplan-Meier analysis revealed significantly higher cumulative rates and earlier occurrence of lymph node metastases (p = 0.0003) and extrathyroidal extension (ETE; p < 0.0001) in the C634R group. The C634R mutation was significantly associated with distant metastases (hazard ratio [HR]: 2.545 [confidence interval (CI) 1.134-5.713]; p = 0.024). Moreover, multivariable analysis identified RET C634R genotype (HR: 6.488 [CI 1.364-30.862]; p = 0.019), increasing age (HR: 1.082 [CI 1.023-1.144]; p = 0.006), and ETE (HR: 9.695 [CI 2.344-40.105]; p = 0.002) to be significantly associated with worse disease-specific survival. Conclusions: Prognosis varied in hereditary MTC patients with RET C634 mutations. Our data highlight that the RET C634R mutation was associated with greater tumor aggressiveness in MTC and a poorer disease-specific survival.

Background: Estrogen may contribute to a higher prevalence of autoimmune thyroid disease (AITD) in women. However, it is unknown whether estrogen-containing cosmetics may be associated with AITD. This study aimed to (1) measure the estrogen concentration in skincare cosmetics sold in China, (2) examine the thyroid autoantibody levels in nude mice after dermal estrogen application, and (3) explore the relationship between skincare cosmetic use and AITD in the Chinese population in a population-based cross-sectional study and hospital-based case-control study. Methods: Skincare cosmetics of variable type and price were collected from various Chinese retail merchants and online shopping platforms to measure the respective estrogen concentrations in the products. Nude mice were smeared with estrogen on the skin to assess their effects on the thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels. A cross-sectional study was conducted in four districts or counties to compare differences in serum TPOAb, TgAb, and thyroid function between cosmetic users and nonusers. A case-control study was conducted in four district hospitals and two city hospitals to explore the association between cosmetic use and AITD. Results: Estriol was detected in 73 of 240 skincare cosmetic products, with a median concentration of 34.58 µg/g. In animal experiments, serum thyroid autoantibodies were significantly increased in mice smeared with (low or high) estriol-containing creams compared with controls (TPOAb, 31.07 ± 6.89 ng/L or 32.22 ± 8.92 ng/L vs. 21.27 ± 6.32 ng/L, p < 0.05; TgAb, 20.94 ± 6.12 ng/L or 19.56 ± 8.35 ng/L vs. 11.28 ± 1.43 ng/L, p < 0.05). In a cross-sectional study, no difference was found in TPOAb, TgAb, and thyroid function between skincare cosmetic users and nonusers (p > 0.05). However, the case-control study revealed a significant association between skincare cosmetics use and the presence of AITD (odds ratio = 1.577, confidence intervals 1.037-2.400, p = 0.033) after adjusting for other related variables. Conclusions: Estriol was found in some skincare cosmetics sold in China. Dermal estriol application could induce thyroid autoimmune reactions in nude mice. Preliminary population-based study data suggest that skincare cosmetic use may be associated with AITD. Prospective cohort studies or randomized controlled trials are needed in the future to confirm a potential association between estriol in skincare cosmetic use and AITD.