Thyroid最新文献

Background: International guidelines now recommend adopting individualized approaches which consider patient preferences when deciding the extent of surgical resection for low-risk differentiated thyroid carcinoma (LRDTC). Information-sharing must be methodical to help patients make informed decisions without feeling overwhelmed by information. Understanding the factors influencing decision-making is therefore essential. Methods: Semi-structured interviews were conducted between May 2023 and June 2024 at two large tertiary referral centers in England, United Kingdom. Consecutive sampling via the multidisciplinary team meetings was used to identify patients newly diagnosed with LRDTC measuring 1-4 cm without adverse features, choosing between hemithyroidectomy and total thyroidectomy, or, if diagnosed following hemithyroidectomy, active surveillance and total thyroidectomy. Clinicians directly involved in their care were approached and recruited, with six consultant thyroid surgeons (five male, one female), and two thyroid cancer nurse specialists (both female), agreeing to participate. All had experience managing over 10 LRDTC patients annually. Transcripts were analyzed using the framework method of thematic analysis. Results: Twenty-four patients were identified, and 19 agreed to participate (13 female, 6 male). Information-sharing was often perceived as a didactic process, leaving patients overwhelmed with complex clinical details. Both groups emphasized tailoring information to meet patients' needs and delivering it in bite-sized portions to enhance comprehension. Key factors influencing individual decisions included a desire among most patients to minimize the number of, and extent of, surgical procedures, the need to preserve the thyroid gland and avoid hormone supplementation, and the patient's ability to accept the cancer recurrence risk. Although autonomy was paramount for patients, providers' recommendations still significantly impacted the final decision. Some clinicians expressed concern that multiple treatment options might confuse patients, instead entrusting decision-making to the multidisciplinary team meetings. Conclusions: This study identified essential information needs for LRDTC treatment decision-making, which can help inform the development of decision-support tools. Multidisciplinary team discussions may need to evolve to allow greater flexibility and support individualized decision-making.

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: We assessed the effectiveness of administering subcutaneous levothyroxine in a medically complex patient, a 51-year-old male who previously underwent total thyroidectomy for papillary thyroid carcinoma. His thyrotropin (TSH) worsened to >100 mIU/L, caused by encapsulating sclerosing peritonitis that led to thyroxine malabsorption and enteral loss of protein-bound thyroxine. Several routes of levothyroxine were evaluated prior to subcutaneous levothyroxine. Methods: Subcutaneous levothyroxine was initiated at a low dose of 100 mcg thrice a week. A pharmacokinetic absorption study was performed to assess the bioavailability of subcutaneous levothyroxine against oral levothyroxine. Results: A 103% increase in free thyroxine at 6 hours post-subcutaneous levothyroxine 100 mcg confirmed effective absorption. Area-under-curve analysis showed that the relative bioavailability of subcutaneous levothyroxine was 8.75 times of oral levothyroxine for our patient. Hence, subcutaneous levothyroxine was initiated, with TSH normalizing 20 days later. Conclusions: Subcutaneous levothyroxine may be an alternative in patients with oral malabsorption.

Background: The treatment paradigm for thyroid eye disease (TED) in the United States has shifted from corticosteroids toward targeted therapies such as teprotumumab. However, it remains unknown whether teprotumumab decreases the need for subsequent treatments for TED compared with intravenous methylprednisolone (IVMP). This study compares the long-term need for additional medical or surgical interventions in TED patients treated with teprotumumab versus IVMP. Methods: A retrospective cohort study identified TED patients treated with IVMP or teprotumumab utilizing the TriNetX Analytics platform. Patients with comorbidities requiring high-dose steroids, prior TED therapy within 6 months, or concurrent TED treatments were excluded. Propensity score matching (PSM) adjusted for baseline demographic and TED-related risk factor differences. Patients were followed for 6, 12, and 18 months after a 6-month washout period. The primary outcome was the incidence of additional TED-related interventions. Secondary outcomes included post-treatment care trajectories, treatment burden, and complexity, assessed through longitudinal pathway analysis. Results: The IVMP cohort included 308 patients, and the teprotumumab cohort included 417; after PSM, each contained 263 patients. No significant differences were found in the incidence of additional TED-related interventions between cohorts. A similar percentage required additional medical therapies (41% vs. 37%, p = 0.423), while fewer in the IVMP cohort underwent additional surgical interventions (3.8% vs. 8.8%, p = 0.019, 4.8% vs. 10.0%, p = 0.040) at 12 and 18 months. Among those needing additional TED interventions, the IVMP cohort exhibited a higher treatment burden and more complex treatment trajectories, requiring a greater average number of treatments (2.34 vs. 1.34 per patient; 32.8% vs. 5.5% requiring ≥3 additional treatments). Conclusions: TED patients treated with IVMP or teprotumumab had similar overall rates of additional interventions. However, IVMP was associated with greater treatment complexity, requiring more varied medical therapies. Teprotumumab-treated patients typically required fewer additional medical therapies and underwent more surgical interventions as a second-line step, suggesting that teprotumumab may simplify the treatment pathway. These data have important implications for patient education and future assessment of the cost-effectiveness of TED therapies.

Background: There is evidence of quality of life (QoL) impairment and weight gain in treated hyperthyroidism. It is not known whether treatment-related weight gain is associated with QoL impairment in this patient group of this cohort. Our primary aim was to examine whether percentage weight gain (PWG) after treatment of hyperthyroidism was associated with QoL impairment. Methods: We enrolled patients with treated hyperthyroidism 6 months to 8 years after diagnosis. We obtained anthropometric measurements from a prospectively completed database. With a cross-sectional study design, we assessed QoL using the thyroid-specific patient-reported outcome (ThyPRO) tool. We pre-specified three dependent variables in ThyPRO: "cosmetic complaints," a composite of "tiredness and overall QoL" and "depressivity and anxiety" domains. We included age, sex, thyrotropin categories, comorbidities, and disease duration as covariates. We applied a generalized linear model (GLM) for the analysis. Results: We included 108 patients, including 68 (63%) females, with a mean (standard deviation [SD]) age 50 (14.5) years. The median weight at diagnosis was 65.5 (interquartile range [IQR]: 58.7, 75.5) kg and BMI was 23.9 (21.9, 27.1) kg/m², and at final evaluation, weight was 72.7 (64.1, 83.8) kg (p < 0.001) and BMI was 26.5 (23.9, 30.8) kg/m² (p < 0.001). The mean (SD) weight gain observed was 7.2 (6.2) kg over a mean (SD) disease duration of 41 (22.5) months. Median PWG was 8.8% (4.3%, 17%). There was a significantly reduced QoL in all comparable domains against general population normative data. PWG was associated with "cosmetic complaints" (odds ratio = 1.11, p = 0.008 via logistic regression; b = 0.47, p = 0.022, q (adjusted p) = 0.033 via GLM) and "tiredness and overall QoL" (b = 0.62, p = 0.011, q = 0.017), but not with the "anxiety and depressivity" domains (b = -0.005, p = 0.661). Conclusions: Our study suggests that weight gain after treatment of hyperthyroidism is associated with a large adverse effect on QoL, with reduced scores on appearance, combined "tiredness and overall QoL" domains of the ThyPRO questionnaire. Management of weight change upon treatment of hyperthyroidism merits further clinical attention and research.

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.