Thyroid最新文献

Background: The optimal extent of surgery and the role of radioactive iodine (RAI) in patients with papillary thyroid carcinoma (PTC) with lateral neck metastasis (cN1b) remain controversial. We aimed to evaluate the oncologic outcomes of lobectomy with lateral neck dissection, total thyroidectomy with lateral neck dissection, and total thyroidectomy with lateral neck dissection followed by adjuvant RAI in patients with intermediate-risk cN1b PTC. Methods: In this multicenter retrospective cohort study, we included patients with cT1-3N1bM0 PTC who underwent thyroidectomy with therapeutic lateral neck dissection between 2010 and 2022. Recurrence-free survival (RFS) and disease-specific survival (DSS) were compared across three treatment groups using Kaplan-Meier. Multivariable cox proportional hazards models were also used to identify independent risk factors for recurrence. Results: We included 593 patients (60.6% female; median age, 58.0 years) who had a median follow-up duration of 71.5 months. We observed no significant differences in RFS (p = 0.19) or DSS (p = 0.40) among the treatment groups of lobectomy, total thyroidectomy, and total thyroidectomy with RAI. Although the total thyroidectomy with RAI group showed a trend toward worse RFS, this was not statistically significant (p = 0.19). In multivariable analysis, older age (hazard ratio [HR] 1.024 per year, confidence interval [CI] 1.007-1.041, p = 0.006), larger primary tumor size (HR 1.026 per mm, CI 1.012-1.041, p < 0.001), larger metastatic lymph node size (HR 1.020 per mm, CI 1.003-1.036, p = 0.017), and extranodal extension (HR 1.741, CI 1.046-2.898, p = 0.033) were independently associated with shorter RFS. Conclusions: RAI may improve RFS in selected patients with extensive nodal disease, but its routine use in all cN1b PTC cases may be unnecessary. Lobectomy or total thyroidectomy without RAI could be appropriate options in lower risk cN1b patients. Further studies are warranted to refine treatment strategies in intermediate-risk cN1b PTC.

Background: Amphibian metamorphosis involves dramatic tissue remodeling, such as intestinal remodeling and tail resorption, driven by thyroid hormones (THs). Among these hormones, T3, the major active form of TH, is locally generated from T4 by type I and type II deiodinases (Dio1 and Dio2), while T3 is inactivated to T2 primarily by type III deiodinase (Dio3). Tissue-specific regulation of T3 availability is thus crucial for orchestrating TH-dependent developmental events. However, little is known about how spatiotemporal regulation of TH activation and inactivation by deiodinases influences tissue remodeling and degradation during frog metamorphosis. Methods: We analyzed the spatiotemporal distribution of deiodinase mRNAs at single-cell resolution using hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) during metamorphosis. To investigate the role of local TH activation or inactivation in vertebrate development, we generated mosaic Dio2- and Dio3-knockdown (KD) Xenopus laevis using CRISPR-Cas9 genome editing. Molecular and morphological analyses were then carried out to determine whether local TH conversion is required for intestinal remodeling and tail resorption. Results: dio2 mRNA expression peaked at stage 61, whereas dio3 mRNA expression showed delayed upregulation, peaking at stage 64 during intestinal remodeling in wild-type animals. dio2 mRNA appeared in fibroblasts located just beneath the epithelial layer at stage 60 and increased in proliferating fibroblasts at stage 62. Interestingly, dio3 expression was colocalized with lgr5 (an adult intestinal stem cell marker)-positive epithelial cells at stage 61. During tail resorption, dio2 and dio3 expressions peaked at stages 62 and 60, respectively. Following gene KD, Dio2KD animals exhibited delayed tail resorption and intestinal remodeling with reduced expression of multiple TH target genes, whereas Dio3KD animals completed metamorphosis more rapidly. Conclusions: Spatiotemporal regulation of TH activation and inactivation by deiodinases is essential for the timing and progression of organ-specific metamorphic events in Xenopus laevis.

Background: Benign thyroid nodules (BTNs) may cause significant compressive symptoms and cosmetic concerns. Thermal ablation has emerged as an alternative to resection, but its impact on quality of life (QOL) has not been thoroughly evaluated. Our objective was to evaluate the existing literature for QOL outcomes, as measured by validated instruments, after BTN thermal ablation. Methods: MEDLINE, Embase, Scopus, EBSCO, and ProQuest Dissertations & Theses Global were searched through December 8, 2025. Studies in English reporting QOL using validated instruments for thermal ablation of BTNs were included. Three reviewers completed article screening, data extraction, and risk of bias assessments (RoBANS 2 and Cochrane Collaboration's tool). Pooled mean differences (MDs) in QOL were calculated for Thyroid-Related Patient-Reported Outcome (ThyPRO) scales using a random-effects model and the inverse-variance approach; pooling was not possible for other instruments due to sparse utilization across varied time points across studies. Results: Of the 72 articles screened, the review included 13, and the meta-analysis included 4. The included studies were randomized controlled trials (3), cohort studies (3), or pre/post studies (7). The baseline sample sizes ranged from 14 to 120. Ablation techniques included radiofrequency (7 studies), laser (3), and microwave (3). QOL instruments included two thyroid-specific (ThyPRO: 7 studies, Patient-Reported Outcome Measure for Parathyroid and Thyroid disease, or PROMPT: 1), one dysphagia-specific (Swallowing Quality of Life tool, or SWAL-QOL: 1), and three generic (2 Short Form scales, SF-12: 2 and SF-36: 4, EuroQol-5 dimension-3 level scale (EQ-5D-3L): 1) instruments. QOL improvements generally became apparent between three and six months; long-term durability was variable. Improvements in overall QOL (8 of 9 studies) were more consistent than improvements in compressive QOL (4 of 5 studies) or cosmetic QOL (2 of 4 studies). ThyPRO domain MDs statistically improved for most scales, although the consistency of improvement across time points varied. MDs exceeded minimal important changes (MICs) for goiter (all four time points); anxiety (≤1 month only); cognition, depressivity, and emotional susceptibility (≤1 month and 12 months only); and cosmetic, hyperthyroid, and eye domains (12 months only). Conclusions: QOL generally improves between three and six months after BTN ablation, although variability is seen across thyroid-specific QOL domains. Study comparability was limited by inconsistent numeric reporting and heterogenous follow-up intervals. Future research should utilize thyroid-specific instruments, extend follow-up beyond one year, include inferential within-subject repeated measures analyses, and contextualize the clinical meaningfulness of QOL changes using MICs.

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.