Thyroid最新文献

Background: Pretibial dermopathy (PTD) is a rare, disfiguring manifestation of Graves' disease. The shared pathophysiology with thyroid eye disease (TED), centered on fibroblast activation via a thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) complex, provides a strong rationale for using the IGF-1R inhibitor, teprotumumab.

Methods: We present a case series of five patients with severe PTD and concomitant TED who were treated with teprotumumab. A review of reported cases in the literature was also conducted.

Results: All patients experienced significant clinical improvement, including regression of skin thickening as well as enhanced functional capacity. Side effects included mild hearing loss, muscle cramps, and fatigue. One patient experienced a severe gastrointestinal event requiring treatment discontinuation, while those experiencing a recurrence of PTD, responded to a second course of therapy.

Conclusions: Teprotumumab showed promising efficacy in the treatment of PTD. Further studies are needed to confirm its durability and safety.

Introduction: BRAF wild-type anaplastic thyroid carcinomas (BRAF^WT-ATCs) have a poor prognosis, in part, due to limited effective therapies. The preliminary results from the phase II ATLEP trial suggest the promising clinical activity of lenvatinib plus pembrolizumab (L/P). We aimed to confirm the real-world efficacy of L/P in BRAF^WT-ATC.

Methods: A retrospective single-center study of patients with BRAF^WT-ATC treated with first-line L/P between January 2016 and July 2024 outside of a clinical trial. The primary endpoints were confirmed overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results: In 36 eligible patients, the median age at treatment start was 64 years (range, 41-84 years). All patients had distant metastases, and 46% had radiological suspicion of locoregional invasion, including that of the trachea, esophagus, and/or internal jugular vein. The most common driver mutations were RAS (39%) and NF1 (19%); 61% had co-occurring TP53 and 50% TERT promoter mutations. In the evaluated specimens, programmed cell death ligand 1 (PD-L1) combined positive score was ≥1 in 96% (27/28), median tumor mutational burden was 2 mut/Mb (interquartile range [IQR], 1-4), and high microsatellite instability (MSI-H) was present in 7% (2/30). Previous therapies for ATC included surgery (69%), definitive- (31%) or palliative-intent (31%) neck external beam radiation, and cytotoxic chemotherapy (9%). The median initial lenvatinib dose was 16 mg (IQR, 10-20 mg). Pembrolizumab dosing was 200 mg Q3 weeks (64%) or 400 mg Q6 weeks (36%). The median time between lenvatinib and pembrolizumab initiation was 0.5 days (IQR, -7.8 to 10.5). With a median follow-up of 39.5 months [confidence interval {CI}, 8.1-54.3], the median OS was 7.7 months [CI, 4.6-22.9], and the median PFS was 6.2 months [CI, 3.1-7.9]. In 33/36 patients evaluable for responses, the confirmed ORR was 36%, and the median duration of the response was 16.0 months [CI, 3.2-28.8]. The best overall response was confirmed complete response in 3 (9%), confirmed partial response in 9 (28%), stable disease in 11 (33%), and progressive disease in 10 (30%) patients. The safety profile was similar to previous studies. Five (14%) patients stopped pembrolizumab due to immune-related toxicity, including pneumonitis (n = 2) and colitis (n = 3). Two patients discontinued lenvatinib due to concern for esophageal or tracheal fistula; however, no further intervention was required in either case.

Conclusions: Our real-world experience with L/P in metastatic BRAF^WT-ATC demonstrates the clinical efficacy and safety of this combination, consistent with prior reports. A prospective clinical trial in the United States is ongoing (NCT#04171622).

Background: In this updated review, we will discuss the role of artificial intelligence (AI) in the assessment of thyroid nodules, cervical lymph nodes, and cytology or histology specimens, followed by guidance for practices wishing to install AI systems.

Summary: To date, six AI platforms for assessing sonograms of thyroid nodules have been cleared by the United States Food and Drug Administration, with generally good performance, especially when compared with that of less-experienced physicians. Multimodality large language models have also been tested in this context, but with less impressive results so far. Software to evaluate lymph nodes and biopsy or surgical specimens shows promise, though no systems have yet reached the marketplace. The process of evaluating and installing an AI system in a practice requires consideration in five areas: information technology, vendor support, effectiveness, usability, and finance. Engagement of people with subject matter expertise in all these domains is recommended, beginning with product selection.

Conclusions: AI tools for the evaluation of thyroid nodules continue to proliferate, and commercial software to assess lymph nodes and slide specimens may soon become available. Attention to detail is critical for successful implementation and operation.

Background: Radioiodine is an effective treatment for hyperthyroidism and thyroid cancer. Little is known about patients' experiences of radioiodine, yet negative beliefs about other novel treatments can influence adherence to precautionary behaviors and side effect experience post treatment. The current study aims to examine the impact of patients' beliefs about their thyroid condition, radioiodine, and their body on precautionary post-radioiodine behaviors and side effects.

Methods: This prospective cohort study enrolled adults receiving a first outpatient dose of radioiodine to treat thyroid cancer or hyperthyroidism. Participants completed questionnaires assessing beliefs and understanding of radioiodine pre-treatment at the end of the initial post-dose restriction period and 4 weeks after receiving radioiodine. We also assessed adherence to precautionary post-treatment behaviors and reported side effects.

Results: Sixty-six patients enrolled in the study, 63 completed the pre-radioiodine and initial post-dose assessments, and 60 completed all three. Overall, participants poorly recalled clinician-imposed post-treatment precautions, but often engaged in additional self-imposed precautions. On average, participants reported 4-5 radioiodine side effects. Participants' beliefs about radioiodine, their thyroid condition, and their body predicted adoption of additional precautions and side effect attribution (P < 0.05 for each).

Conclusions: Patients receiving radioiodine have poor recall and may under-adhere to required postdose precautions while adopting unnecessary self-imposed precautions. Patients with maladaptive beliefs before treatment appear to find radioiodine more burdensome and intrusive during the first 4 weeks after treatment.

Background: Familial nonmedullary thyroid carcinoma (FNMTC) occurs when three or more family members are affected by usually papillary thyroid carcinoma (PTC), the most common form of NMTC. While the heritability to NMTC is among the highest of all cancers, the genetic determinants among NMTC families are not well understood. Here, we aim to understand the contribution of rare noncoding germline variants in the etiology of FNMTC.

Methods: We previously reported whole-genome sequencing (WGS) and linkage analysis in 17 PTC families and reported on 41 protein-coding variants in 40 genes that cosegregated with PTC in 11 of the families. Herein, we further leveraged our WGS data to include noncoding variants in our analysis for all 17 families. We hypothesized that most of the pathogenic noncoding variants would be located in theoretical or empirically determined regulatory regions that demonstrate at a minimum, basal thyroid expression, a positive family linkage score, and co-segregation among PTC-affected individuals. To test this hypothesis, we adopted a unique filtering strategy to identify variants that occurred in known DNA elements and transcription factor binding sites, near regions known to impact on gene expression or splicing in thyroid tissue, and/or in characterized thyroid enhancers. We annotated variants using two analyses (ENCODE and transcription factor binding site) within the BasePlayer software. We separately analyzed (1) expression quantitative trait loci, (2) splicing quantitative trait loci, and (3) thyroid enhancers. We then ranked variants according to predicted pathogenicity and performed Sanger sequencing in all individuals of each family.

Results: In total, 121 variants were selected based on in-silico prediction and our custom ranking analysis in each pedigree. Of these, 56 variants showed cosegregation among all PTC-affected individuals and were absent from unaffected individuals. This included candidate variants from five of the six PTC families for whom no protein-coding variants were previously found.

Conclusion: Our data suggest that noncoding variants are important in the etiology of FNMTC and provide a framework for identifying noncoding germline variants using a novel approach. Further studies are needed to functionally characterize these variants to better understand the molecular mechanism of their pathogenicity.

Background: The risk of hypothyroidism after hemithyroidectomy is not well defined in the pediatric population. We sought to determine the incidence of hypothyroidism after hemithyroidectomy in children and the clinical factors associated with this risk.

Methods: This is a retrospective cohort study of consecutive pediatric patients (<19 years of age) who underwent hemithyroidectomy in a pediatric thyroid center between 1998 and 2023, with data available on postoperative thyroid function and/or levothyroxine (LT4) treatment. The primary outcome was the composite of persistent hypothyroidism (thyrotropin [TSH] ≥ 5 mIU/L) or LT4 treatment (PersHypo/LT4). Secondary outcomes were persistent hypothyroidism and transient hypothyroidism. Univariable and multivariable survival analysis and logistic regression were used to evaluate associations of these outcomes with clinical characteristics.

Results: A total of 136 eligible patients (85% female) underwent hemithyroidectomy at a median (range) age of 15.4 (0.14-19.0) years. The median (interquartile range) postsurgical follow-up was 1.10 (0.15-3.2) years for thyroid function and 1.76 (0.38-4.3) years for LT4 treatment status. PersHypo/LT4 occurred in 27/136 patients (20%), with an estimated risk of 18.1% [CI: 12.1-26.6%] at 1 year and 27.5% [CI: 18.7-39.2%] at 5 years. PersHypo/LT4 occurred within 12 months in 21/27 cases (78%) and after 12 months in 6/27 (22%). PersHypo/LT4 was associated with preoperative TSH (hazard ratio 1.89, [CI: 1.31-2.74], p = 0.001), and preoperative TSH ≥ 2 mIU/L optimally distinguished patients with high (58.8%) versus low (12.8%) 5-year risk of PersHypo/LT4 (receiver operator characteristic AUC 0.73, [CI: 0.60-0.85]). The presence of thyroperoxidase (TPO) antibodies was independently associated with increased risk of PersHypo/LT4 (OR: 7.37, [CI: 1.09-49.9], p = 0.041). Persistent hypothyroidism occurred in 14/128 patients (11%), with an estimated 5-year risk of 12.9% [CI: 7.7-21.1%]. Severe hypothyroidism occurred in 5/136 patients (3.7%), and transient hypothyroidism occurred in 22/136 patients (16%).

Conclusions: Persistent hypothyroidism or LT4 treatment occurs in 27.5% of children within 5 years after hemithyroidectomy, usually in the first postoperative year. Preoperative TSH < 2 mIU/L may identify children at low risk, whereas preoperative TSH ≥ 2 mIU/L, particularly in conjunction with TPO antibodies, may identify children at high risk. Transient hypothyroidism also occurs commonly but may not require treatment. These data should inform preoperative counseling and postoperative monitoring around hemithyroidectomy in children.

Background: Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer with a median survival of less than six months. So far, no therapies offering a survival benefit are established. Thus, new therapeutic approaches are urgently needed. In general, genetic alterations leading to ATC increase PI3K and MAPK/ERK signaling and include mutations in receptor tyrosine kinases and tumor suppressor genes. They often occur together with the loss of p53, the most prevalent mutation in human ATC. Among such alterations are mutations and rearrangements of the anaplastic lymphoma kinase (ALK) gene.

Methods: To study ATC and potential treatment options, we generated a mouse model with inducible thyrocyte-specific expression of constitutively active mutant ALK^F1174L and homozygous deletion of Trp53 due to a Cre recombinase under control of the thyroglobulin promoter (thyroglobulin [Tg]-Cre^ERT2+/0;lox-stop-lox (LSL)-ALK^F1174L/+;Trp53^LoxP/LoxP mice, here referred to as Trp53^KO/ALK^F1174L mice). Moreover, we established several primary thyroid cancer cell lines harboring ALK^F1174L and Trp53^KO and investigated the effects of ALK inhibition in vitro and in vivo.

Results: Median survival of Trp53^KO/ALK^F1174L mice was severely reduced, and the mice showed massively enlarged thyroids. Histopathology confirmed the development of locally invasive and metastatic ATC. Treatment of primary Trp53^KO/ALK^F1174L ATC cells with the ALK inhibitor TAE-684 decreased AKT and ERK phosphorylation and induced a dose-dependent cytotoxicity. Trp53^KO/ALK^F1174L mice treated with TAE-684 showed significantly extended median survival compared with the solvent group (66 days vs. 18 days, p < 0.0001).

Conclusions: Our data demonstrate that the combination of ALK^F1174L mutation with Trp53 loss leads to the development of ATC. This study provides the first functional data supporting the use of ALK inhibitors in patients with ALK-driven ATC. Our novel ATC mouse model and the derived cell lines offer valuable tools to explore the molecular characteristics of ATC, especially signaling pathway activation and tumor microenvironment, and to test novel therapeutics for the treatment of advanced thyroid cancers.

Background: Artificial intelligence (AI) chatbots are increasingly being used by patients to obtain medical information. Comparison between platforms with specialty-specific physician assessment remains limited. This study compares the quality, factual accuracy, readability, and consistency of responses generated by four publicly available AI chatbots when answering patient-centered questions about thyroid radiofrequency ablation (RFA).

Methods: We conducted a cross-sectional analysis of chatbot-generated responses using 20 standardized clinical questions about thyroid RFA. Responses from ChatGPT-4, Gemini, Copilot, and Perplexity were evaluated by six blinded physician reviewers experienced in thyroid RFA using 5-point Likert scales for global quality and factual accuracy. Higher Likert scale scores indicated better performance. Readability and response length were analyzed with established metrics. Statistical significance was defined as p < 0.05.

Results: Gemini achieved the highest mean scores for global quality (4.08 ± 0.87) and accuracy (3.76 ± 1.05), with significantly better performance than ChatGPT and Copilot (p < 0.005). ChatGPT responses were significantly longer and more readable. Score variability across questions was lowest for Gemini. Copilot and Perplexity ranked lowest across most domains. Question-level analysis identified specific prompts that best discriminated between platforms.

Conclusions: AI chatbot performance varied across platforms for thyroid RFA queries. Chatbots were generally reliable for straightforward factual information but were less dependable for judgment or context-dependent assessments. These AI tools should supplement, not replace, clinician-vetted patient education and institutional materials.

Background: The prognostic value of unstimulated serum thyroglobulin (Tg) levels for structural recurrence in patients with low- to intermediate-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy but did not receive radioactive iodine (RAI) therapy remains unclear. This study aimed to determine Tg cutoff values and evaluate the role of dynamic Tg monitoring in risk stratification in these patients. Methods: We retrospectively analyzed 9753 patients with low- to intermediate-risk DTC who underwent total thyroidectomy without RAI at 11 Korean tertiary hospitals. Serum Tg levels were measured under thyrotropin suppression (<2 mIU/L) at 6, 12, and 24 months postoperatively using high-sensitive assays (functional sensitivity, <0.2 ng/mL). Optimal Tg cutoffs were determined by receiver operating characteristic curves and survival analyses. Results: Higher postoperative unstimulated Tg levels consistently predicted structural recurrence, with an optimal cutoff of 0.3 ng/mL (area under the curve: 0.815, 0.772, and 0.816 at 6, 12, and 24 months, respectively). A Tg ≥ 0.2 ng/mL, the Korean Thyroid Association (KTA) guideline cutoff for biochemical remission (excellent response), showed high sensitivity for recurrence. Tg ≥ 5.0 ng/mL at 6 months, a KTA-defined threshold for a biochemical incomplete response, independently predicted an elevated recurrence risk. Kaplan-Meier curves showed stepwise declines in recurrence-free survival with increasing Tg levels. Notably, even Tg < 0.2 or < 0.3 ng/mL were associated with recurrence if levels rose over time. Conclusion: Unstimulated Tg levels are strongly associated with the risk of structural recurrence in patients with DTC who have undergone total thyroidectomy without RAI. The current cutoff values of 0.2 ng/mL and 5.0 ng/mL were clinically relevant, and Tg kinetics over time further improved risk stratification. These findings provide the first large-scale evidence from an East Asian cohort and underscore the importance of early, serial Tg assessment in this growing patient population.