Thyroid最新文献

Background: The coexistence of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF^V600E) and telomere reverse transcriptase promoter (TERT-p) mutations is considerably associated with aggressiveness and poor prognosis in papillary thyroid carcinoma (PTC). However, the association between gross findings and genetic alterations in PTC remains unknown. We aimed to investigate the association between clinicopathologic features, including macroscopic features, and the coexistent BRAF^V600E and TERT-p mutations in patients with PTC. Methods: We retrospectively analyzed 375 cases of PTC surgically resected between January 2018 and October 2023 at a single institution, based on the presence of BRAF^V600E and TERT-p double mutation. Clinicopathologic features, including gross features on the cut surface of tumors, were evaluated. Subsequently, the association between clinicopathologic features and mutation status was statistically examined. Cox proportional hazard models were used to analyze the impact of molecular pathological features on disease-free survival (DFS). Results: The BRAF^V600E and TERT-p double mutation was identified in 78 (20.8%) patients among the PTC cases and was significantly correlated with shorter DFS. Multivariable analysis revealed that factors such as relatively older age (≥55 years) (odds ratio [OR] = 12.083, 95% confidence interval [CI] 4.498-32.456), larger tumor size (>2.0 cm) (OR = 2.722, CI 1.104-6.712), lobulated tumor margins (OR = 16.114, CI 3.155-82.296), papillary excrescences on the cut surface (OR = 17.573, CI 3.462-89.201), solid-cut surface (OR = 4.012, CI 1.084-14.849), minimal extrathyroidal extension (ETE) (OR = 4.156, CI 1.209-14.282), gross ETE (OR = 6.517, CI 1.734-24.490), and Ki-67 labeling index (LI) (≥5%, OR = 12.145, CI 4.354-33.877) were significantly associated with the double mutation. Conclusions: The BRAF^V600E and TERT-p double mutation in PTC was significantly associated with relatively old age, larger tumor size, lobulated configuration in tumor margin, papillary excrescences on the cut surface, solid-cut surface, ETE, and high Ki-67 LI. These features are suggestive of the presence of the double mutation and should be analyzed at the molecular level in patients with PTC.

Introduction: The increasing incidence of differentiated thyroid carcinoma (DTC) in children and adolescents has become a growing concern. This study provides the first extensive assessment of incidence patterns and temporal trends of pediatric DTC in Germany, using the best available data from the German Malignant Endocrine Tumor (MET) Registry and the German Childhood Cancer Registry (GCCR) covering a period of 25 years. Patients and Methods: We conducted a register-based incidence and time series analysis, identifying all children and adolescents diagnosed with DTC at ages 0-17 years between 1997 and 2021 in Germany, as recorded in the German MET Registry and/or the GCCR. Age-specific and age-standardized incidence rates (ASR) over time, average annual percentage changes (AAPC), and cross-tabulations were used to evaluate incidence and temporal patterns. Results: We identified 469 DTC cases, including 85.7% papillary thyroid cancer and 9.4% follicular thyroid cancer. The average ASR for the period 1997-2021 was 1.16 per million, with higher rates in females compared with males (1.64 vs. 0.72 per million, respectively). Incidence rates increased with increasing age. The overall ASR increased from 0.84 per million in 1997-2001 to 1.48 per million in 2017-2021, with an AAPC of 3.46% [confidence interval or CI: 2.12-4.83]. The increase was most pronounced in adolescents aged 15-17 years (AAPC: 6.79% [CI: 4.43-9.19]). The proportion of incidentalomas rose from 5% in 1997-2001 to 26% in 2017-2021, yet we observed no marked shift in tumor size between symptomatic and incidental cases. Conclusions: Our study revealed a significant increase in pediatric DTC incidence in Germany, most pronounced among adolescents. The observation of an increasing incidence mirrors global trends and presents a complex public health challenge. While improved detection likely contributes to this trend, the stable tumor size distribution suggests that other factors are also in play. The rising detection of incidentalomas suggests enhanced diagnostic practices unrelated to symptoms of thyroid neoplasia. These findings highlight the need to carefully evaluate diagnostic and screening practices in pediatric populations.

Background: The "neutral" thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro. During these earlier studies, we developed a mouse monoclonal antibody (MC1) specific for a peptide (amino acid 322-340) in the region (MC1-Mab) which was able to induce thyroid cell stress and apoptosis when administered in vivo. Methods: In order to examine the effect of in vivo generated N-TSHR-Abs, rather than an acutely administered monoclonal antibody, we immunized Balb/c mice with the hinge region peptide over 18 weeks. Serum TSHR antibodies, specific TSHR hinge region antibodies, serum thyroglobulin (TG) and anti-TG as well as thyroxine and thyrotropin (TSH) levels were examined to evaluate the response to the immunization. Histological examination of the thyroid glands and flow cytometry of spleen T cells, B cells and macrophages were also performed to explore the underlying mechanisms. Results: We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular destruction with follicular cell apoptosis, M1 macrophage infiltration, thyroglobulin release, and induction of thyroglobulin antibodies. This resulted in hypothyroidism with increased TSH levels. Conclusion: This study demonstrated that endogenous neutral antibodies to the TSHR could induce thyroid cell damage from apoptosis and M1 macrophage infiltration and resulted in hypothyroidism.

Background: Thyroid cancer is the most common endocrine neoplasm in China. Questions regarding the extent of patient involvement in shared decision-making (SDM) processes persist; this is particularly pertinent to patients considering treatment options for low-risk papillary thyroid cancer (PTC). In this study, we aimed to explore Chinese young adults' experiences of SDM relating to the choice of treatment for low-risk PTC. Methods: The study used a qualitative descriptive design and semistructured interviews. Interviews were conducted with 24 patients (ages ranging from 18 to 38 years; 4 men and 20 women) diagnosed with low-risk (PTC) between March 2023 and May 2024. Twenty-two of 24 patients' tumor size measured 1 cm or smaller; the largest tumor size measured 1.47 cm. Reflexive thematic analysis was used to identify key themes from the transcribed interviews. Results: The analysis revealed that the SDM experiences of young patients with low-risk PTC involve four themes: challenges in information sharing; reasons for information seeking; factors influencing decision making; and self-positioning in treatment decision making. Three self-positions relating to treatment decision making were identified. These included dependent positioning, which reflects a "paternalistic" decision-making pattern; collaborative positioning, reflecting a "sharing" of decision making; and autonomous positioning, reflecting an increased sense of personal responsibility for both managing their health and engagement in decision making. Limited treatment options being offered, overuse of medical terminology, and communication gaps between clinicians and patients were the main challenges described during the information-sharing process. Information that needs persisting after physician-patient consultations resulted in active information-seeking behavior. The key variables identified in this study that potentially affected the decision-making process were future personal considerations, language used to discuss cancer, and negative emotions. Conclusions: These results highlight the necessity of adopting flexible strategies when supporting collaborative treatment decision making in the context of the doctor-patient interaction for low-risk PTC. Based on these findings, clinicians can take measures to enhance the quality of SDM by inquiring about patients' role preferences, providing details of the full range of treatment options, and encouraging patients to share their preferences and concerns relating to possible treatment options.

Background: Thyroid ultrasound examinations (TUEs), conducted as part of the Fukushima Health Management Survey (FHMS), were initiated to monitor the health status of residents after the Fukushima Daiichi Nuclear Power Plant accident owing to concerns regarding the increased incidence of thyroid cancer among children, as observed after the Chernobyl Nuclear Power Plant accident. This study reported the clinicopathological characteristics of patients with thyroid cancer diagnosed through the FHMS and treated at the Fukushima Medical University Hospital. Methods: Data regarding the clinicopathological characteristics of patients with thyroid cancer were collected and evaluated in this descriptive study. Results: Among the 263 patients diagnosed with thyroid cancer as of September 2021, 220 patients with cytologically diagnosed thyroid cancer were treated as referrals from the FHMS. The median (interquartile range) age at the time of diagnosis was 18.6 (16.2-20.3) years. The median maximum tumor diameter was 13.0 (10.4-18.0) mm. To reduce surgical invasiveness, 199 patients (90.1%) underwent unilateral lobectomy. Pathological findings were suggestive of papillary thyroid carcinomas (PTC) in 216 (98.2%) patients; among them, 205 patients had PTC of the classical type. In addition, 216 (98.2%) patients had stage I disease. Cancer cell extension in the sternothyroid muscle or perithyroidal soft tissues and microscopic lymphovascular invasion were observed in 112 (50.9%) and 123 (55.9%) patients, respectively. No differences were observed between the two age groups (<18.6 years and ≥18.6 years) in terms of the clinical or pathological characteristics of thyroid cancer: risk classification (p = 0.69) and American Thyroid Association pediatric risk level (p = 0.24). Compared with those from previous reports, few surgical complications were observed. Conclusions: Patients with thyroid cancer diagnosed with TUEs underwent safe and minimally invasive operations, and careful postoperative follow-up was provided. The pathological findings of the detected thyroid cancers indicated that the majority were classical papillary carcinomas, and approximately half of the patients had extrathyroidal or lymphovascular invasion. No differences were observed between the two age groups in terms of the clinical or pathological characteristics of thyroid cancer.

Objective: To describe the epidemiology of thyroid eye disease (TED). Methods: A population-based cohort of all Olmsted County, Minnesota, residents who had newly diagnosed TED between January 1, 2005, and December 31, 2020, was identified through the medical diagnostic index of the Rochester Epidemiology Project. Individuals aged 18 years and older were included. Incidence rates and point prevalence were calculated. Baseline disease characteristics and progression of disease were described. Results: We identified 83 incident patients, of whom 75 (90.4%) were female. The overall age and sex adjusted incidence for the U.S. population were 5 cases/100,000 person-years. Females had higher incidence (8.9 cases/100,000 person-years) compared with men (1 case/100,000 person-years). The distribution of peak incidence rates by 5-year age groups differed between male and female, in which females had peak incidence rates in the age groups 60-64 years and 80-84 years (18.3 cases and 18 cases/100,000 person-years, respectively), while male had peak incidence rate in the age group 70-74 years (5.7 cases/100,000 person-years). No clear trend was identified for the yearly incidence between 2005 and 2020. The overall estimated point prevalence per 100,000 was 65 (CI, 53.3-78.7). Prevalence was 114.5 (CI, 92.6-139.9) for females and 13.8 (CI, 6.8-24.6) for males (p < 0.001). Factors associated with disease progression were severity of soft tissue involvement (hazard ratio [HR] 7.7; CI, 2-29.8) and presence of diplopia (HR 2.5, CI, 1.2-5.1). Conclusions: Incidence rates for TED remained stable over the past two decades, yet lower than that in the previous study from our population. Females continue to have the peak incidence rate a decade earlier than males, and the majority of disease burden is present after the age of 50 years. Appropriate resources should be devoted to furthering education, management, and research into this condition.

Importance: There is uncertainty as to whether treatment of subclinical hypothyroidism (SCH) is associated with cardiovascular outcomes. Objectives: To determine whether levothyroxine replacement therapy decreases the risk of major adverse cardiovascular events (MACE) among individuals with SCH defined as having a thyrotropin (TSH) level between 5 and 10 mU/L. Design: We conducted a population-based cohort study using a prevalent new-user design. Setting: The study utilized data from the United Kingdom Clinical Practice Research Datalink. Participants: We identified a base cohort of individuals aged ≥18 years with incident SCH defined as having at least two TSH levels between 5 and 10 mU/L within one year between 1998 and 2018. We matched 76,946 levothyroxine treated to 76,946 untreated individuals based on age, sex, calendar time, duration of SCH, and time-conditional propensity score. We compared individuals with SCH treated with levothyroxine with individuals with no treatment. Exposure: Levothyroxine treatment versus no treatment. Main Outcome Measures: The primary outcome, MACE, was defined as a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular-related mortality. Results: The mean age of the study cohort was 62.8 years, and 76.5% were women. During a median follow-up time of 1.6 years (interquartile range: 0.5-4.2), the incidence rate for MACE among individuals treated with levothyroxine was 12.8 per 1000 person-years; confidence interval (CI): 12.2-13.3 and 13.9 per 1000 person-years; CI: 13.4-14.3 among nontreated individuals. Levothyroxine treatment was associated with a small decreased risk of MACE (hazard ratio: 0.88; CI: 0.83-0.93). Conclusions: Levothyroxine treatment of SCH was associated with a small decreased risk of MACE. However, given the observational nature of the study, residual confounding should be considered in the interpretation of this finding.

Background: Receptor tyrosine kinase (RTK) fusions of RET, NTRK1/3, and ALK are enriched among pediatric thyroid cancer patients with metastatic and persistent disease, and their oncoproteins represent attractive drug targets. Methods: We performed RNA-sequencing in a papillary thyroid cancer (PTC) lacking other frequent driver alterations. Results: We report a novel RTK fusion, TG-insulin-like growth factor 1 receptor gene (IGF1R), in a 17-year-old female patient with angioinvasive follicular variant PTC. The in-frame fusion protein preserves the cholinesterase-like domain of TG with dimerization properties and the transmembrane and kinase domain of IGF1R. The tumor sample shows increased IGF1R mRNA expression and tyrosine kinase phosphorylation, augmentation of Mitogen activated protein kinase (MAPK) transcriptional output genes, and decreased NIS levels. Conclusions: We reveal a novel targetable kinase fusion oncogene in thyroid cancer which is not incorporated in different thyroid-specific sequencing panels. The integration of IGF1R fusion screening in the next versions of thyroid-specific targeted next-generation sequencing panels may be beneficial to thyroid cancer patients.

Background: The rearranged during transfection (RET) proto-oncogene fusion is common in papillary thyroid cancer (PTC), varying across ethnic groups. However, comprehensive comparisons of RET fusion types are limited. This study aims to identify predominant RET fusions and analyze their clinicopathological characteristics in a cohort of Chinese thyroid cancer cases. Methods: This single-center retrospective cohort study analyzed thyroid cancer data, utilizing next-generation sequencing on formalin-fixed, paraffin-embedded tissue samples. Detailed clinicopathological data of thyroid cancer cases with RET fusions were collected. Results: Among 2300 thyroid cancer cases, RET fusions were exclusively found in PTC or differentiated high-grade thyroid carcinoma (DHGTC) cases (2234 cases), absent in other types (66 cases). Of the 2234 PTC or DHGTC cases, 113 (5.06%) exhibited RET fusions, including 100 primary cases. Coiled-coil domain containing 6 (CCDC6)-RET fusions predominated (78.0%, 78/100), with nuclear receptor coactivator 4 (NCOA4)-RET fusions representing 22.0% (22/100). NCOA4-RET fusions were more prevalent in patients aged 45 years and older (54.5% vs. 28.2%, p = 0.021) and DHGTC cases (p < 0.05) and associated with higher rates of lymph node metastases (90.9% vs. 67.9%, p = 0.032). CCDC6-RET fusion exhibited a higher prevalence of Hashimoto's thyroiditis (HT) (67.9% vs. 22.7%, p < 0.001) and elevated thyroglobulin antibody levels (14.11 [1.86-174.32] IU/mL vs. 2.01 [1.14-15.41] IU/mL, p = 0.018). Moreover, CCDC6-RET fusion predominantly occurred in classical PTC (56.4%, 44/78) and infiltrative follicular PTC (17.9%, 14/78), whereas NCOA4-RET fusion was more frequent in classical PTC (36.4%, 8/22), solid PTC (27.3%, 6/22), and DHGTC (27.3%, 6/22). RET fusions with compound mutations were associated with older age (≥45 years) and bilateral thyroid involvement. Follow-up data showed a higher recurrence rate in the RET fusion group compared with the BRAF^V600E mutation group (5.0% vs. 0.0%, p = 0.018). Although the NCOA4-RET group showed a numerically higher recurrence rate compared with CCDC6-RET (9.1% vs. 3.8%), this difference was not statistically significant (p = 0.559). Conclusions: RET fusions are specific to PTC or DHGTC cases among Chinese thyroid cancer cases. CCDC6-RET and NCOA4-RET fusions exhibited distinct clinicopathological features, with NCOA4-RET being more aggressive.