Thyroid最新文献

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.

Background: Treatment for Graves' hyperthyroidism (GH) in patients with Graves' orbitopathy (GO) remains a topic of debate. This study aimed to investigate the outcome of GO following glucocorticoids, depending on the chosen thyroid treatment. Methods: This retrospective cohort study included 49 consecutive patients with GH and moderate-to-severe, active GO, as defined by the European Group on Graves' Orbitopathy guidelines. Twenty-four patients were treated with radioactive iodine (RAI) and 25 with methimazole (MMI). All patients were administered intravenous methylprednisolone. Follow-up visits occurred at weeks 24, 48, and 72. The primary endpoint was the overall outcome of GO at week 24. Response was defined as a change in at least two of the following eye features: reduction ≥1 point in clinical activity score; proptosis reduction ≥2 mm; eyelid aperture reduction ≥2 mm; increase in eye ductions ≥8 degrees. Results: Follow-up duration was 72 weeks for both groups (interquartile range 66-72 for RAI and 48-72 for MMI). The proportion of responders for week 24 overall GO outcome was greater in RAI (54.1% vs. 16%; odds ratio [OR] 6.2 [confidence interval (CI): 1.6-23.6], p = 0.0075), but it increased in MMI at weeks 48 and 72, with no differences between groups. There was a trend indicating a better response in RAI regarding individual eye features. Improvement in GO-specific quality of life questionnaire at week 24 was trendily more pronounced in RAI (responders 50% vs. 28% in MMI; OR = 2.5 [CI: 0.7-8.4], p = 0.11), although results were similar in both groups at later time points. At week 24, only one patient (4%) in RAI and three (12%) in MMI experienced worsening of GO. Fifty-nine adverse events were recorded among 36 patients, with no differences between groups, except for infections, which were more frequent in RAI (53.8% vs. 15.3% in MMI; OR = 6.41 [CI: 1.7-23.9], p = 0.0056). Conclusions: RAI appears to be associated with an earlier response of GO to intravenous glucocorticoids. In the long term, a conservative approach also seems to be effective. RAI appears to be relatively safe when patients are concurrently treated with glucocorticoids. However, randomized clinical trials are necessary to confirm these findings.

Introduction: Thyroid dysfunction and mood disorders are chronic health conditions with a significant impact on quality of life. This study aimed to investigate the association between thyrotropin (TSH) and clinically relevant depression (CRD) in patients with and without mood disorders, in a population-based sample. Methods: This retrospective cross-sectional study included all consecutive adults (≥18 years) who had TSH and completed the Patient Health Questionnaire (PHQ-9) within 6 months of the index visit, between October 2016 and May 2021, at the University of Utah Health. Data on demographics, hypothyroidism diagnoses, TSH, thyroid hormone replacement (THR), PHQ-9, antidepressant (AD) medications, and mood disorder diagnoses (using the International Classification of Diseases, 10th Revision, Clinical Modification codes; Major depressive disorder single episode-F32, recurrent-F33, persistent mood disorder-F34, bipolar disorder-F30+F31, and mood disorder not otherwise specified-F39) were extracted electronically. CRD was defined as PHQ-9 ≥ 10. t-Test and chi-square test were used to compare continuous and categorical variables, respectively. Logistic regression models were formulated to evaluate the association between TSH and CRD, after adjusting for covariates. Results: The cohort included 33,138 patients, mean age 42.41 ± 16.10 years, 80.67% Caucasian, 69.10% females, and mean PHQ-9 score 10.11 ± 6.94. A total of 45.23% (n = 14,989) patients had a diagnosis of mood disorders, and 49.70% had CRD. Patients with mood disorders were more likely to be female, Caucasian, non-Hispanic/Latino, on AD, had hypothyroidism diagnoses, on thyroid medications, had higher mean PHQ-9 scores, and had CRD. TSH level was associated with an increased odds of CRD (odds ratio [OR] = 1.01, confidence interval [CI], 1.01-1.02, p < 0.009) after adjusting for age, sex, body mass index, Charlson Comorbidity Index, and use of THR and AD. Both the low TSH and high TSH groups showed increased odds of CRD, with respective ORs of 1.19 (CI: 1.04-1.37) and 1.26 (CI: 1.13-1.40). Conclusions: Thyroid dysfunction is associated with an increase in the odds of depression. Future longitudinal cohort studies are recommended to investigate the association between thyroid function and incident depression.