Thyroid Research最新文献

Background: Discriminating the epigenetic landscapes of coincidental benign thyroid nodules (particularly follicular adenoma subtypes) from papillary thyroid carcinoma (PTC) remains a critical unresolved challenge, impeding mechanistic insights into their divergent pathogenic trajectories.

Methods: To address this knowledge gap, we performed integrative multi-omics profiling of histologically paired benign thyroid nodules and PTC lesions from the same patients, synergizing chromatin accessibility mapping (ATAC-seq), whole-exome sequencing, transcriptomics, and ATAC-seq-derived extrachromosomal circular DNA (eccDNA) detection.

Results: Three pivotal mechanisms emerged from our cross-omics analyses to delineate the benign-malignant dichotomy. First, chromatin architecture interrogation revealed spatially colocalized PTC-specific accessible regions with somatic mutation hotspots, suggesting coordinated interplay between epigenetic remodeling and genomic instability in malignant transformation. Second, we uncovered ARHGEF28 and ARHGEF24 as novel potential benign-specific master regulators, where TEAD4-binding motif enrichment in benign-hyperaccessible chromatin drives their coordinated overexpression, forming a self-reinforcing regulatory loop unique to benign thyroid nodules. Third, eccDNA-centric profiling delineated a different regulatory paradigm: benign thyroid noduless exhibited preferential enrichment of T-cell signaling related elements on eccDNA scaffolds, whereas PTCs eccDNA were enriched in the DNA replication signaling pathways. This multidimensional atlas not only maps lineage-specific regulatory topologies of thyroid neoplasms but also establishes the ARHGEF28/24-TEAD4 axis as potential association with benign lineage.

Conclusions: By elucidating chromatin-based thresholds of malignant progression, our findings provide a molecular framework for differential diagnosis and mechanistic dissection of transformation checkpoints.

There was no systematic study on myxedema coma (MC), this review summarizes clinical research on MC conducted over the past 20 years. Publications from 2004 to 2024 were retrieved from databases and included. A total of 584 published cases and 114 unpublished cases of MC were systematically analyzed. The estimated incidence rate of MC was 0.12 (95% confidence interval [CI], 0.10%-0.14%) per million per year. Precipitating factors were identified in 77.6% (95%CI: 73.7%-81.5%) of patients with MC. The overall mortality rate was 38.8% (271/698, 95%CI: 34.9%-42.7%), with shock and multiple organ failure (MOF) being the most common causes of death. The results demonstrated that 88.9% (95%CI: 86.9%-90.9%) of patients with confirmed MC had altered mental status (AMS). Approximately 71.9% (95CI:68.0%-75.8%) of patients with MC had hypothermia, and 66.2% (95CI:62.3%-70.1%) had a heart rate < 60 bpm. Seven signs (hypoglycaemia, hypotension, hypercarbia, hoarseness, dry skin, constipation, and puffiness) showed both negative and positive predictive values below 70% and were consequently excluded from the diagnostic criteria. Combined with literature reviews and statistical analysis, proposed diagnostic criteria for MC are presented. It is generally recommended to confirm the presence of decreased FT3 and/or FT4 levels as a necessary criterion for establishing a diagnosis of MC. Early recognition, clinical suspicion, prompt thyroid hormone replacement, supportive measures, and appropriate management of coexisting problems remain the cornerstone of managing this fatal endocrine emergency. Future research directions for MC should focus on: clinical validation and refinement of diagnostic criteria, elucidating the pathophysiological mechanism underlying MC, and conducting clinical studies to compare the efficacy of different treatment regimens.

Background: CD44v6 is a membranous antigen upregulated in solid tumors and a promising molecular radiotherapy target, especially in anaplastic thyroid carcinoma (ATC). A Phase 1 trial recently launched to evaluate the lutetium-labeled anti-CD44v6 antibody [¹⁷⁷Lu]Lu-DOTA-AKIR001 in CD44v6-positive solid tumors. Given limited data in non-ATC, we assessed CD44v6 immunoreactivity in tumors that may progress to a radioiodine-refractory state.

Materials and methods: An exploratory cohort of 33 tumors (30 papillary thyroid carcinomas [PTCs], 3 poorly differentiated thyroid carcinomas [PDTCs]) was screened using the VFF-7 antibody, supported by detailed iodine concentration, genetic, and RNA sequencing data. A validation cohort of 40 oncocytic thyroid carcinomas (OTCs), 28 additional PDTCs, and one differentiated high-grade thyroid carcinoma was also screened using two antibody clones, VFF-7 and VFF-18.

Results: In the exploratory cohort, 10 of 33 tumors (30%) showed focal or diffuse CD44v6 expression, while the rest were negative. Among OTCs in the validation cohort, 15 of 40 (38%) were partially or diffusely positive, and in PDTCs, 14 of 28 (50%) showed focal or diffuse staining. The VFF-7 and VFF-18 clones produced similar patterns.

Conclusions: Substantial subsets of non-ATCs express CD44v6, indicating that some patients may be candidates for [¹⁷⁷Lu]Lu-DOTA-AKIR001 radiotherapy, particularly when conventional treatments are exhausted.

Purpose: Patients with active, moderate-to-severe Graves' orbitopathy require immunosuppressive treatments to reduce inflammation and morbidity. Since 2021 EUGOGO lists Mycophenolate-sodium (MPS) as first-line-treatment, which lead to a change in treatment regimens. In our center MPS was administered mainly for patients at risk for deterioration (e.g. unstable thyroid function, smoker etc.) or as second-line treatment. To augment the limited data we analyzed our real-world cohort retrospectively.

Methods: We analyzed all consecutive patients of our tertiary referral center (2019-2023) with a complete data set, who either received MPS simultaneously with intravenous methylprednisolone (IVMP), or after a first course of IVMP.

Results: We evaluated the data of 172 patients. Ninety-five were eligible for analysis. Clinical Activity Score showed a significant decrease between baseline (BL) and primary endpoint 6 months (3.9 ± 0.9 vs. 2.4 ± 1.4, p < 0.0001). Inactivation was achieved in 60% of all patients at 6 months and in 77% at 12 months. Deviation, motility, upper eye lid retraction and proptosis showed no significant changes after 6 months. TSH-receptor-antibody-levels (TRAb) showed a significant decrease at 3 and 6 months (p < 0.0001). 10.5% developed DON. Multiple logistic regression showed a significant influence of irradiation after BL for inactivation (OR 6.18, 95% CI: 1.08 to 48.99).

Discussion: While inactivation is most often achieved, the severity of the disease in form of fibrosis (lid retraction, motility) and proptosis is not reversed. Further rehabilitative surgery is needed and patients should still be closely monitored for DON. Other immunosuppressants could be more effective even in IVMP resistant GO and should be subject to randomized head-to-head trials.

Background: Swallowing complaints are common following total thyroidectomy, though an exact mechanism of patient-reported swallowing symptoms following thyroidectomy is currently lacking. This secondary, blinded analysis of data collected in a randomized, controlled clinical trial hypothesized that patients randomly assigned to the central neck dissection group would exhibit increased aspiration and pharyngeal residue on videofluoroscopic swallowing evaluation, and reduced patient-rated swallowing outcomes, as compared to patients randomized to thyroidectomy alone. We further hypothesized that blinded analysis would reveal worse swallowing function two-weeks post-surgery when compared to their pre-operative status to explain qualitative patient-reported dysphagia symptoms.

Methods: Thirty-two participants randomized to total thyroidectomy treatment with or without central neck dissection underwent pre- and post-surgical evaluation of swallowing outcomes, including videofluoroscopic Penetration/Aspiration Scale ratings, Normalized Residue Ratio Scale measures of valleculae and pyriform sinus residue, and EAT-10 patient-rated outcomes.

Results: No statistically significant differences were found post-surgery between randomized treatment groups for patient-rated EAT-10 scores (p = 0.2406), penetration/aspiration scale (p = 0.4465) or Normalized Residue Rating Scale scores for either vallecular or pyriform sinus sites. When group data were combined for analysis of differences between pre- and post-operative swallow performance, no statistically significant differences were found in patient-rated EAT-10 scores (p = 0.1374), penetration/aspiration scale (p = 0.7588) or Normalized Residue Rating Scale scores.

Conclusions: Measures of penetration/aspiration and pharyngeal residue failed to substantiate perceptions of post-operative dysphagia reported by patients undergoing total thyroidectomy with or without central neck dissection.

Trial registration: ClinicalTrials.gov Identifier NCT02138214.

Objectives: Serum thyroglobulin (Tg) is a key biomarker in the post-surgical monitoring of differentiated thyroid cancer (DTC). However, inter-assay variability among different immunoassay platforms can impact clinical interpretation, particularly at low Tg concentrations. This study aimed to compare the analytical performance and concordance of three widely used Tg immunoassays, Access (Beckman Coulter, Tg-B), Atellica (Siemens, Tg-A), and Liaison (Diasorin, Tg-L), with a focus on their agreement across clinically relevant Tg ranges.

Methods: A total of 103 residual serum samples from subjects with or without thyroid pathology were analyzed using Tg-B, Tg-A, and Tg-L. Correlation analysis, Bland-Altman plots, and concordance rates were evaluated across three Tg concentration intervals: <2 ng/mL, 2-50 ng/mL, and > 50 ng/mL. Tg-B was used as the reference method for comparison.

Results: All three assays demonstrated strong overall correlations. Tg-L showed a very strong correlation with Tg-B (ρ = 0.89), with moderate agreement at Tg < 2 ng/mL. Tg-A also correlated well with Tg-B (ρ = 0.92), though agreement declined slightly at higher concentrations (> 50 ng/mL). The concordance rate for detecting undetectable Tg (< 0.2 ng/mL) was 96% for Tg-L and 98% for Tg-A when compared to Tg-B. Bland-Altman analysis revealed a significant negative bias for Tg-L versus Tg-B, while Tg-A and Tg-B showed no significant difference. A significant discrepancy was also observed between Tg-L and Tg-A.

Conclusions: Although the three Tg immunoassays demonstrated high correlation, notable differences emerged at lower and higher Tg levels, likely due to assay-specific antibody characteristics and calibrator variability. Our findings underscore the need for re-baselining when switching methods in longitudinal follow-up. However, the use of residual serum samples from a heterogeneous population, including individuals with and without thyroid pathology limits the direct clinical generalizability of the results and underscores the need for further validation in well-characterized post-thyroidectomy DTC cohorts.

Background: Thyroid cancer is the most common endocrine tumor, impacting patients' quality of life and contributing to a significant societal burden. This study aims to estimate the global burden of thyroid cancer attributable to High Body Mass Index(HBMI) over the past 30 years.

Methods: The mortality rates, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) attributable to HBMI for thyroid cancer were extracted. A generalized linear model with a Gaussian distribution was used to calculate the estimated annual percentage changes (EAPCs) in ASRs, quantifying the temporal trends in the global burden of thyroid cancer due to HBMI. The strength and direction of the association between the Social Developmeant Index (SDI) and DALY rates were measured using Spearman's rank correlation. The Bayesian age-period-cohort (BAPC) model was used to predict deaths patterns of thyroid cancer from 2020 to 2035.

Results: Globally, the DALYs for thyroid cancer increased from 1.49 in 1990 to 1.68 in 2021, with an EAPC of 0.377 (95% CI: 0.342-0.411). 127 countries or regions showed an upward trend. This trend was particularly pronounced in low SDI, middle SDI, and low-middle SDI regions, while a declining trend was observed in high SDI and high-middle SDI regions.The global ASR of death(ASDR) and DALYs were all higher in females than in males.From 2020 to 2035, the global burden of thyroid cancer, measured in DALYs and ASDR, are both projected to exhibit a gradual upward trend.

Conclusions: High Body Mass Index is associated with thyroid cancer. Comprehensive control of body weight may help mitigate or even prevent the development of thyroid cancer, providing valuable data for future prevention and control efforts.

Background: Iodine is essential to thyroid hormone production, and both excess and deficiency can cause thyroid dysfunction in infants. While urinary iodine concentration (UIC) is used to assess population iodine status, there is no gold standard for determining iodine status in individual infants. Our study aimed to examine the clinical use of UIC in the investigation of thyroid dysfunction in hospitalised infants.

Methods: We examined hospital records of infants (age < 24 months) admitted to The Children's Hospital at Westmead who had UIC collected in the context of thyroid dysfunction between 2007-2009 and 2017-2021, two time periods separated by changes in public health measures for iodine nutrition and local clinical practice.

Results: Of 152 infants, 13.8% had UIC in iodine deficient range (WHO population-based definition: UIC < 100 µg/L) and 53.9% in iodine excess range (UIC ≥ 300 µg/L). Highest quartile UIC (> 1432 µg/L) was significantly associated with pre-test clinician suspicion of iodine excess, identification of source of iodine exposure, higher percentage of premature babies, and those with cardiac anomalies or who required surgery. Median free thyroxine (fT4) level was significantly lower in the highest UIC quartile group compared to the lower three quartiles (9.4pmol/L [interquartile range 7.8-vs 13.7] vs. 12.7 pmol/L [10.3-15.6]; p = 0.004). While median TSH was elevated in all UIC quartiles in this group, there were no significant differences in the levels between the UIC quartile groups.

Conclusions: Extremely high random UIC can be helpful to confirm clinical suspicion of iodine excess in hospital-based infants, taken in the context of thyroid dysfunction in critical illness. The degree of thyroid dysfunction associated with high UIC in this clinically complex and often premature patient population may be better measured by the fT4 level rather than the degree of TSH elevation.