Thyroid Research最新文献

Background: This study aims to investigate the effects of iodinated contrast media (ICM) exposure on thyroid function in patients with subclinical hyperthyroidism.

Methods: The study included 46 patients with subclinical hyperthyroidism who presented to the cardiology outpatient clinic and underwent angiographic imaging procedures. Thyroid function tests (TSH, fT3, fT4) of the patients before and after the procedure were analyzed retrospectively. Patients were divided into two groups as low volume (< 200 ml) and high volume (≥ 200 ml) according to the volume of contrast medium received. Pre- and post-procedure comparisons as well as analyses according to low and high-volume exposure were performed.

Results: After the procedure, 50% of the patients became euthyroid and 41.3% remained in the same group (subclinical hyperthyroidism). 2 patients (4.3%) developed clinical hyperthyroidism, and another 2 patients (4.3%) developed clinical hypothyroidism. TSH values increased significantly after the procedure (p < 0.01), but no significant change was observed in fT3 and fT4 values.

Conclusions: In patients with subclinical hyperthyroidism, thyroid function mostly remained stable or became euthyroid after ICM exposure. However, a group of patients developed clinical hypothyroidism or hyperthyroidism. These results suggest that patients with subclinical hyperthyroidism should be closely monitored when using ICM. Long-term follow-up will contribute to a better understanding of the possible risks in this patient group.

Background: Pretibial myxoedema (PTM), a rare extrathyroidal manifestation of Graves' disease (GD), is characterized by dermal glycosaminoglycans (GAGs) deposition. Current therapies (e.g., glucocorticoids) show limited efficacy with high relapse rates. Emerging evidence implicates JAK-STAT pathway activation via thyrotropin receptor antibodies (TRAb) in the pathogenesis of PTM, suggesting JAK inhibitors, such as Tofacitinib, as potential therapy.

Case presentation: A 39-year-old man with GD and Graves' orbitopathy (GO) presented with bilateral pretibial non-pitting edema and itchy erythematous nodules. Histopathology from skin biopsy confirmed GAGs deposition and elevated TRAb (> 40 IU/L). After transient response to intralesional glucocorticoids, oral tofacitinib (5 mg twice daily) was initiated. Significant resolution of edema (body surface area: 12%→3%) and GO occurred within 1 month, sustained over 6 months without adverse events.

Conclusion: Tofacitinib demonstrated rapid and durable efficacy in refractory PTM, likely by suppressing JAK-STAT-mediated fibroblast activation and pro-inflammatory cytokine release. This supports its role as a potential targeted oral therapy for PTM.

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.