Thyroid最新文献

Background: The introduction of molecular testing (MT) of cytologically indeterminate thyroid nodules (ITNs) alone has not impacted thyroidectomy rates. Due to this, we evaluated the incremental diagnostic value of various clinical variables in addition to MT results, in predicting the risk of malignancy (ROM) among ITNs. Methods: This prospective observational study included 1024 consecutive ITNs that underwent reflexive ThyroSPEC MT between Jul 30, 2020, and Oct 30, 2023. A multivariable logistic regression model was built to assess the relationship between histology outcomes and clinical variables, including nodule discovery by palpation, ultrasound risk categories, maximum nodule size, Bethesda category, Bethesda atypia, and ThyroSPEC categories. A total of 332 out of 1024 patients who underwent surgery and had complete data for all variables were included in the model. A nomogram was subsequently developed based on the model. Results: The model achieved a cross-validated AUC of 0.831 (95% confidence intervals: 0.787-0.874). Patients with high-risk mutations or malignant molecular markers exhibited significantly higher odds (152.79 times) of malignancy compared to those with mutation-negative or benign molecular marker results. Patients with maximum nodule size >5 cm have 4.34 times higher odds of malignancy than those 0-2 cm. The presence of nuclear atypia increased the odds of malignancy by 4.26 times, while ultrasound malignancy risk category 5 increased the odds of malignancy by 2.89 times compared to categories 1-3. Positive palpation discovery increased the odds by 1.83 times. The integrated ROM estimated from the regression model is significantly associated with the surgery type (p < 0.001). In the low (0-30%) and intermediate ROM (31-70%) categories, lobectomy alone is the most common surgery (61% and 70%, respectively), while in the high ROM (>70%) category, total thyroidectomy dominates (62%). Conclusions: Although MT alone played an important role in decision-making regarding surveillance versus surgery in our study population, integrating MT results with additional clinical variables improved the malignancy risk prediction for ITNs. Our results highlight the importance of contextualizing MT results within an integrated interdisciplinary thyroid nodule diagnostic pathway.

Background: We investigated if thyroid nodule taller-than-wide (TTW) feature and sphericity metrics are helpful in separating benign neoplastic thyroid nodules (follicular and oncocytic adenomas) from follicular thyroid carcinomas (FTC) and oncocytic thyroid carcinomas (OCA). Methods: This is a retrospective study of TTW sonographic feature as reported by radiologists and nodule sphericity metrics at two academic health systems. Surgical pathology reports for benign and malignant follicular and oncocytic neoplasms, non-neoplastic nodules (hyperplastic and adenomatoid), and classic papillary thyroid cancers (PTC) were extracted from enterprise data warehouses. We independently reviewed each ultrasound and recorded nodule dimensions to identify nodules that were TTW and determine if the proportion of TTW nodules is different in benign and malignant thyroid nodules of various histologies. We also evaluated the sphericity index and sphericity ratio, two quantitative measures of how close the 3D shape of the nodule is to a sphere. Results: In total, 1110 nodules were analyzed: 209 non-neoplastic nodules (hyperplastic and adenomatoid), 398 benign neoplasms (follicular and oncocytic adenomas), and 503 malignant neoplasms (FTC, OCA, PTC, and follicular variant-PTC [FV-PTC]) and noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP). There was no statistical difference for the TTW feature when follicular and oncocytic adenomas were compared with FV-PTC, OCA, FTC, and NIFTP (χ², p = 0.08, sensitivity of 28% [confidence interval 23-24%]), when follicular adenoma was compared with FTC (χ², p = 0.64) or when oncocytic adenoma was compared with OCA (χ², p = 0.08). Benign and malignant neoplasms were more likely than non-neoplastic nodules to be TTW (χ², p = 0.02). In contrast, the sphericity index and sphericity ratio were significantly different in most comparisons of benign and malignant nodules (Wilcoxon, p < 0.03) except for oncocytic tumors. Conclusions: TTW shape has limited utility in distinguishing benign follicular and oncocytic neoplasms from malignancy. This sonographic feature was more common among all benign and malignant neoplasms when they were compared as a group to non-neoplastic nodules, which suggests this sonographic feature is an indicator of neoplastic growth (benign or malignant) but not cancer. Alternative methods, such as measures of sphericity, are needed to distinguish benign and malignant oncocytic and follicular neoplasms.

Background: In China, thyroid cancer (TC) is the most common cancer in females and the fifth most common cancer in males. TC overdiagnosis leads to overtreatment, lifelong medical care, and side effects. This study systematically quantifies the epidemiological profile of TC incidence in China, as well as estimating TC incidence attributable to overdiagnosis. Methods: Data were derived from the Cancer Incidence in Five Continents databases. Age-standardized incidence rates (ASIRs) per 100,000 person-years were calculated using the world standard population. Joinpoint regression and age-period-cohort models were conducted to examine temporal ASIR trends and period effects, respectively. We estimated TC incidence attributable to overdiagnosis among patients aged 15-84 years by comparing shapes of age-specific curves with those observed before diagnostic practices. Results: In 2013-2017, there were 37,862 and 117,979 new TC cases in males and females in China, respectively, with ASIRs of 6.9/100,000 and 21.1/100,000. Significant upward trends were observed from 1993 to 2017, with average annual percent changes being 14.7% for males and 16.2% for females. Incidence rate ratios of period effects markedly increased from 1.0 to 61.8 for males and from 1.0 to 42.9 for females from 1993 to 2017. Overdiagnosis accounted for 83.5% (31,455/37,685) and 88.7% (104,222/117,509) of cases in males and females in 2013-2017, respectively, yielding ASIRs of 5.9/100,000 and 19.1/100,000. ASIRs attributable to overdiagnosis in urban populations (6.9/100,000 for males and 21.7/100,000 for females) were significantly higher than in rural populations (1.3/100,000 and 6.4/100,000). Among the 25 included provinces, ASIRs attributable to overdiagnosis ranged from 0.3/100,000 in Sichuan to 18.5/100,000 in Shanghai in males and from 0.1/100,000 in Shanxi to 49.4/100,000 in Shanghai in females. The national ASIRs attributable to overdiagnosis increased from 2.6/100,000 in 2008-2012 to 5.9/100,000 in 2013-2017 for males and from 9.2/100,000 to 19.1/100,000 for females. Conclusions: The incidence rates of TC have considerably increased over the past 25 years in China. Rapidly increasing trends and considerable geographic variations in TC incidence attributable to overdiagnosis highlight the need to adjust TC screening strategies and clinical practices, optimize healthcare resource allocation, and monitor the impacts of TC overdiagnosis on population-level health.

Background: The incidence of pediatric thyroid cancer has been increasing, and care varies due to socioeconomic disparities or differing practice patterns. Clinical guidelines call for care in multidisciplinary teams to minimize variance and provide protocols. Based on expert opinion, we hope to describe the form and function of such multidisciplinary teams for pediatric thyroid programs. Methods: A modified Delphi method to reach consensus statements over two rounds. Twenty-one experts with varying backgrounds responded to each statement on a 9-point Likert scale. Upon completion of the survey, the panel reviewed and shared the results and comments from participants and modified the statements accordingly. This process was repeated such that statements reached consensus, were deemed no consensus, or had no change in the mean. Results: There was an 88% and 83% completion rate for Rounds 1 and 2, respectively. A consensus was observed that there is a distinct definable model of care for pediatric thyroid patients. No consensus was reached for the age range of patients, but programs should care for children with medullary thyroid cancer, differentiated thyroid cancer, and patients with genetic predisposition syndromes. A comprehensive team includes, but is not limited to, a thyroid surgeon, a pediatric endocrinologist, a high-volume fine-needle aspiration (FNA) proceduralist, an oncologist, a nuclear medicine physician, a pediatric pathologist, a pediatric radiologist, and a nurse coordinator. Necessary support services involve care coordination, access to a multidisciplinary tumor board, ability to perform ultrasound-guided FNA, and access to molecular testing. The panel emphasized cross-institutional collaborative research prioritizing guidelines development, disease-specific outcomes, treatment toxicity, and the molecular landscape of thyroid cancer. Conclusions: These consensus statements can be beneficial in improving multidisciplinary care, by describing which elements of pediatric thyroid programs should be consistent across institutions. Overall, the panel agreed that pediatric thyroid centers should provide integrated care with defined team members, services, resources, and research priorities. This model has the potential to standardize various aspects of clinical care and enhance our ability to study patient outcomes, improve health care delivery, and increase scholarly collaboration.

Background: The current American Joint Committee on Cancer 8th edition staging system on thyroid cancer describes outcomes for populations of patients with well-differentiated thyroid cancer (WDTC) and not individual patients. The aim of this study was to create a clinical nomogram that can be used to predict survival in individual patients with WDTC. Methods: A single institutional cohort of 8535 patients with WDTC treated with primary surgery at the Memorial Sloan Kettering Cancer Center was used to create a predictive nomogram for disease-specific survival (DSS) as a retrospective cohort study. The nomogram was created using DSS as the dependent variable, and the independent variables used were sex, age, pathology subtype, and TNM stage. An external validation cohort of 519 patients from three different international centers was used to assess the accuracy and generalizability of the nomogram. Results: Sex, age, pathology subtype, T stage, N stage, and M stage were significant predictors of DSS on univariable analysis. The nomogram created using all these variables showed an extremely high concordance index (0.963; SE 0.012). This nomogram was validated on the external patient cohort with a high concordance index (0.810; SE: 0.070). Conclusions: We describe a predictive nomogram that accurately predicts DSS in individual patients with WDTC. The external validation illustrates its generalizability. This nomogram will help in counseling individual patients on prognosis and may identify patients who could benefit from more aggressive therapy.

Background: The international medullary thyroid carcinoma (MTC) grading system (IMTCGS) has been proposed as an independent tool to predict disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). We aimed to evaluate the performance of IMTCGS in our series of sporadic MTCs and to compare its predictive power with conventional prognostic factors. Methods: In a retrospective cohort study, we evaluated data from 314 patients with sporadic MTC, all managed at the Pisa University Hospital. We divided patients according to the extent of the disease at diagnosis into localized (183/314, 58.3%) (confined to the thyroid), regional (100/314, 31.8%) (limited to the neck, involving surrounding thyroid tissues and/or regional lymph nodes), and distant (31/314, 9.9%) (distant metastases) disease. Data about somatic mutations were available in 212/314 (67.5%) patients. Expert pathologists differentiated high- and low-grade tumors. Results: According to the IMTCGS, 115/314 (36.6%) had high- and 199/314 (63.4%) patients had low-grade tumors. Patients with high-grade tumors showed higher preoperative calcitonin levels compared with low-grade (542 vs. 76 pg/mL, p < 0.01) as well as larger tumor size (2.3 vs. 1.1 cm, p < 0.01) and more frequent multifocality (22.6 vs. 12.1%, p = 0.01), minimal extrathyroidal extension (30.4 vs. 9.5%, p < 0.01), and lymph node metastases (63.5 vs. 27.6%, p < 0.01). Overall, patients with high-grade showed lower DSS, LRFS, and DMFS (p < 0.01). Grouping the whole cohort according to different disease extent at diagnosis, only in the case of localized disease, patients with high-grade tumors had significantly lower LRFS compared with low-grade. Similarly, in the other subgroups, we did not identify any difference in DSS, LRFS, and DMFS. Moreover, in the case of RET aggressive mutations, no differences in DSS, LRFS, and DMFS were observed between high- and low-grade tumors. Conclusions: We confirmed the usefulness of IMTCGS in predicting DSS, LRFS, and DMFS. However, it finds the best utility in patients with a lower risk of recurrence and mortality, identifying those rare cases with more aggressive clinical behavior. Conversely, when laterocervical lymph nodes (N1), distant metastasis (M1), or RET mutations, particularly M918T or indels, are already present at diagnosis, the role of IMTCGS in predicting DSS, DMFS, and LRFS becomes less relevant.

Background: Thyroid-associated ophthalmopathy (TAO, aka thyroid eye disease [TED], Graves' orbitopathy) remains poorly understood and inadequately treated since its initial description. It is disfiguring, can threaten vision, and represents an autoimmune process closely associated with thyroid disease. Unambiguous connections linking TAO to the glandular maladies of Graves' disease (GD) remain incompletely clarified. Detecting the thyrotropin receptor (TSHR) in periocular tissues suggests that this cell-surface protein represents a shared autoantigen with the thyroid gland, but we now know that its expression is ubiquitous. Most patients with TAO have relatively high circulating levels of activating anti-TSHR autoantibodies. Emerging more recently is the importance of insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of TAO. The TSHR/IGF-IR signaling complex apparently drives circulating fibrocytes and the unique phenotypes of fibroblasts inhabiting the TAO orbit (GD-OF). Methods: The PubMed database was scanned for articles dating back to the earliest time periods covered. Keywords used for primary searches included thyroid-associated ophthalmopathy, Graves' orbitopathy, TED, orbit, TSH receptor, IGF-I receptor, and autoimmune thyroid disease. Secondary searches used numerous other search terms. Results: GD-OF have been characterized extensively as being particularly responsive to the immunological factors and key effectors in TAO pathogenesis. Both TSHR and IGF-IR are overexpressed by GD-OF and CD34⁺ fibrocytes and form a signaling complex. They are activated through this TSHR/IGF-IR complex to produce large amounts of hyaluronan and express multiple cytokines. This complex mediates cellular responses to pathogenic IgGs in TAO. CD34⁺ fibrocytes and CD34⁺ OF also express relatively high levels of multiple thyroid autoantigens. Identifying IGF-IR as a key component of a receptor complex and its intertwining signaling activities with those of TSHR has led to a targeted medical therapy for TAO. This therapy involves the selective systemic inhibition of IGF-IR. Conclusions: Much has been learned over the preceding decades about the pathogenesis of TAO. Among these is the identification of IGF-IR as a pivotal component underpinning the disease. This has led directly to development of an effective targeted therapy. Important gaps in our understanding persist, and current therapies have limitations. Thus, despite these advancements, considerably more remains to be achieved.