Thyroid最新文献

Background: The association between hypothyroidism and mortality remains inconsistent across studies. We evaluated the associations of overt and subclinical hypothyroidism with all-cause and cardiovascular mortality in a large Chinese cohort. Methods: This retrospective cohort study included 70,276 adults aged 25 to 84 years who underwent routine health examinations at a large medical center in northern China between January 1, 2017, and December 31, 2022. Thyroid function was categorized as euthyroidism, overt hypothyroidism, or subclinical hypothyroidism. Mortality data were obtained through linkage with national death registries. Cause-specific Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality. Subgroup analyses were conducted by age and diabetes status. Results: Among 70,276 participants, 853 (1.2%) had overt hypothyroidism, and 2436 (3.5%) had subclinical hypothyroidism. During a median follow-up of 5.1 years (interquartile range, 3.6-6.0), 359 deaths occurred. Compared with individuals with euthyroidism, overt hypothyroidism was associated with increased all-cause (HR, 2.01; confidence interval [CI], 1.17-3.45) and cardiovascular mortality (HR, 2.70; CI, 1.18-6.19). Among individuals with diabetes, overt hypothyroidism showed a stronger association with all-cause mortality (HR, 5.45; CI, 2.46-12.07) than among those without diabetes (HR, 1.19; CI, 0.56-2.54) (p for interaction = 0.045). Subclinical hypothyroidism was associated with increased all-cause mortality among participants younger than 50 years (HR, 3.28; CI, 1.31-8.23), including those with thyrotropin (TSH) levels <10 mIU/L (HR, 3.36; CI, 1.34-8.43), but not among those aged 50 to 69 years (HR, 0.32; CI, 0.08-1.31) or 70 years or older (HR, 1.00; CI, 0.51-1.98) (p for interaction = 0.022). Conclusions: Overt hypothyroidism was associated with increased mortality, particularly in individuals with diabetes. Subclinical hypothyroidism was associated with increased mortality risk only in younger adults, even at modest TSH elevations.

Background: A finely tuned balance between excitation and inhibition is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders. Understanding GABAergic neuron maturation processes is thus currently a major challenge in basic neuroscience. Thyroid hormones (THs) are required for the proper maturation of parvalbumin (PV)-expressing GABAergic interneurons in the mouse neocortex. However, the timeline of this TH action has yet to be elucidated. The aim of the present study was to define better the time window during which THs promote the postnatal maturation of PV neurons in the mouse neocortex. Methods: We used genetically engineered mouse models expressing dominant-negative mutations of the TH nuclear receptor α1 (TRα1). The consequences of blocking TH signaling at different times in development were assessed in PV neurons of the somatosensory cortex, in terms of histology and gene expression. Results: Histological observations in mice revealed that the action of THs during the first three postnatal weeks was necessary to initiate the expression of PV and the elaboration of a specialized extracellular matrix called the perineuronal net (PNN). By contrast, after the third postnatal week, TH action on PV neuron maturation appeared to be somewhat dispensable. Transcriptome analysis of neocortical GABAergic neurons two weeks after birth identified a small set of putative target genes for TRα1. Several of these genes are involved in the postnatal remodeling of the repertoire of ion channels within PV neurons and in the elaboration of PNNs. Conclusions: These data suggest that THs act as a timer to define the temporal boundaries of the critical period of heightened cortical plasticity, which plays a fundamental role in the development of neuronal circuits. Unveiling the molecular underpinnings of TH action in PV neurons may help understand better neurological disorders associated with alterations of TH signaling, such as hypothyroidism, resistance to THs, or Allan-Herndon-Dudley syndrome, but also more widely, neurological disorders associated with an imbalance in the excitation/inhibition ratio in the brain, including attention-deficit/hyperactivity disorder, autism, and epilepsy.

Background: Brain metastases from thyroid cancer (TC) are rare but signify an advanced stage of the disease with poor survival outcomes. This study aimed to identify prognostic factors associated with brain metastasis-specific survival (BMS) in patients with brain metastases from TC. Methods: A systematic review and meta-analysis were conducted. Data were extracted from studies retrieved from PubMed, Scopus, Embase, and MEDLINE up to July 18, 2025. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) for potential prognostic factors. Results: A total of 24 studies, including 301 patients with brain metastases from TC, were included. BMS was 18 months (confidence interval [CI], 1.07 to 3.56). Key prognostic factors associated with decreased BMS included anaplastic thyroid carcinoma (HR, 3.3; CI, 1.06 to 10.3; p = 0.04), poorly differentiated thyroid carcinoma (HR, 1.95; CI, 1.07 to 3.56; p = 0.03), poor performance status (Eastern Cooperative Oncology Group >1) (HR, 2.62; CI, 1.69 to 4.05; p < 0.001), multiple brain metastases (HR, 1.89; CI, 1.24 to 2.89; p = 0.004), and the presence of distant metastases (HR, 1.97; CI, 1.13 to 3.44; p = 0.018). Neither the size nor the anatomical location of brain metastases was significantly associated with BMS. Conclusions: Brain metastases from TC are associated with poor survival, with key prognostic factors including aggressive tumor subtypes, poor performance status, multiple brain metastases, and the presence of extracranial metastases, particularly in the lungs. These findings highlight the need for a multidisciplinary approach and the importance of systemic disease control in improving outcomes for this challenging patient population.

Background: There is limited information about the clinical behavior and no standardized treatment guidelines for primary thyroid lymphoma (PTL). Prognostic factors and treatment outcomes remain poorly defined despite diagnostic and therapeutic advancements. We evaluated PTL survival outcomes and treatment strategies, using a large population-based cohort from the Tokyo Cancer Registry (TCR), a government-operated database that systematically collects cancer incidence and outcome data in Tokyo, Japan. Patients and Methods: This retrospective, population-based study analyzed PTL cases registered in 2012-2020 in the TCR. The patients (n = 401) were identified through an International Classification of Diseases for Oncology, third edition topography code C73.9 (thyroid gland) and nonthyroidal lymphoma ICD-10 codes. Results: The median follow-up was 3.3 years (interquartile range, 1.2-5.5 years). Disease-specific mortality was concentrated in the first two years postdiagnosis, particularly in the initial six months. Advanced age (≥80 years) and diffuse large B-cell lymphoma (DLBCL) were associated with poorer overall survival (OS) and disease-specific survival (DSS). The current lymphoma staging systems do not significantly differentiate survival outcomes. Favorable outcomes were observed with localized treatments, including curative surgery alone, for stage IE PTL. Conclusions: Disease-specific mortality was highest in the first two years, particularly the first six months, highlighting this as a critical management period and the importance of timely treatment. Despite recent treatment advances that have improved the overall prognosis and reduced prognostic differences among disease stages, age at diagnosis and histological subtype remain key OS and DSS determinants, with older patients and DLBCL patients experiencing poorer outcomes. Notably, favorable outcomes were observed in selected Stage IE cases treated with surgery alone, suggesting that less-intensive treatment may be appropriate for certain PTL patients.

Background: No international consensus exists on the selection and reporting of outcomes after differentiated thyroid cancer (DTC) surgery, hindering assessment of new treatments and guideline formation. Therefore, we aimed to develop an international core outcome set (COS) to be measured and reported in future studies investigating surgical treatment for DTC, as well as in clinical practice. Methods: COS development consisted of three phases: (1) collecting an initial outcome list through a literature review, (2) a two-round international Delphi process with experts and patient representatives, and (3) international expert panel meeting to finalize the COS. A steering committee including experts from varying medical (sub-)specialties and a patient representative from the Dutch Thyroid Patient Organization advised on the study protocol, Delphi rounds, and expert panel meeting. Experts were identified through scientific associations, international guidelines on DTC, ClinicalTrials.gov, and last authors of key studies and suggestions from the steering committee. The outcomes from the literature review were presented in successive rounds to experts and patient representatives to assess their importance for inclusion in the DTC surgical COS. Delphi results were analyzed for each stakeholder group on a 1-9 Likert scale. Consensus-in was defined as 70% or more of participants in both stakeholder groups rating the outcome 7-9 or 90% in one group. Consensus-out was defined as 70% or more in both groups rating the outcome 1-3. Consensus-out required agreement across both groups. Results: A total of 125 experts and 7 patient representatives from 35 countries across 5 continents completed all rounds. After two rounds, consensus was reached for 17 outcomes. Of these, 13 outcomes were ratified during the expert panel meeting: recurrence, persistent disease, location of metastatic lymph nodes, number of retrieved metastatic lymph nodes, postoperative thyroglobulin levels, surgical completeness, permanent recurrent laryngeal nerve paralysis due to surgery, permanent postoperative hypoparathyroidism, 30-day postoperative complication rate, accidental intraoperative injury to adjacent organ, unplanned reoperation rate, 30-day postoperative mortality, and quality of life. Conclusions: This international consensus on the COS for DTC surgery promotes consistent and appropriate outcome selection in clinical practice and research and may be incorporated into future study designs. Future steps include defining some outcomes.

Background: There has been growing interest in the application of artificial intelligence (AI) in thyroid cancer care, given its potential to enhance diagnostic accuracy, predict patient outcomes, and personalize treatment plans. However, bias introduced during the development of AI algorithms used for thyroid cancer care poses a significant challenge, as biased datasets can lead to disparities in diagnosis and treatment recommendations, particularly in underrepresented populations. This systematic review evaluates the current landscape of AI models for thyroid cancer, focusing on demographic representation and potential biases. Methods: This systematic review was registered on PROSPERO (ID: CRD42024519238) and conducted in accordance with the Cochrane handbook and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search was performed on EMBASE, PubMed, and Google Scholar up to January 2024. Studies were included if they involved AI models for thyroid cancer management and provided demographic details. Data extraction and risk-of-bias assessments were conducted by two independent reviewers. Results: A total of 197 studies were included in the review, with the majority focusing on diagnosis (n = 133) and prediction/prognosis (n = 47). Most studies predominantly involved participants from China (n = 124) and the United States (n = 26), with more female participants (n = 12,410) than males (n = 4222). Ethnicity data from 197 studies (248,896 participants) revealed a significant underrepresentation of East Asians (14.6%) compared with their global thyroid cancer prevalence (18.7%), while White (26.8%) and Black participants (26.8%) were overrepresented relative to their global prevalence (20.7% and 11.3%, respectively). Socioeconomic factors, marital status, and race/ethnicity were less frequently considered in the models. Conclusion: The findings highlight significant gaps in the diversity and representativeness of data used in thyroid cancer AI models. Current models align with epidemiological trends but lack comprehensive demographic inclusion. As such, more representative AI models are required that account for all aspects of a patient's demographics and sociocultural background. Future research should focus on developing and validating more equitable AI models to improve thyroid cancer care across diverse populations.

Background: Free thyroxine (FT4) reference intervals (RIs) provided by many laboratories do not adequately represent the differences in FT4 levels observed across age groups, limiting their usefulness in the diagnosis and management of disease, most particularly at the extremes of age. Interpretive criteria specific to neonates, young children, and older adults are rarely provided. This work was undertaken to develop comprehensive age-based RIs from birth to age 100 to provide clinicians with precise context for result interpretation. Methods: RIs were calculated through multi-modal decomposition (MMD) analysis performed on de-identified retrospective FT4 results from specimens submitted for routine testing by direct dialysis at a commercial reference laboratory. Intervals were validated using a separate data set. The study population for MMD analysis included individuals from age 0 days to 100 years who submitted specimens for FT4 testing. Results: A total of 1,862,273 results were included in the analysis. MMD analysis yielded 14 distinct RIs by age. FT4 intervals were broadest, with higher upper reference limit (URL) and lower reference limit (LRL) at birth, narrowing toward adult ranges throughout childhood. A mild increase in the URL was observed in older adults. Conclusions: The development and validation of FT4 RIs provides interpretive criteria for FT4 results for patients throughout the lifespan. By providing RIs for distinct neonatal, pediatric, and adult age groups, this work enables clinicians to evaluate FT4 results in the appropriate context, allowing more accurate classification of abnormal results.