Thyroid最新文献

Background: Differentiated thyroid cancer (DTC) is the most prevalent cancer of thyroid and is among the most frequently diagnosed cancers in the United States. The practice guidelines of the American Thyroid Association (ATA) for DTC management in adult patients (previously combined with thyroid nodules) were published initially in 1996, with subsequent revisions based on advances in the field. The goal of this update is to provide clinicians, patients, researchers, and those involved in health policy with rigorous, comprehensive, and contemporary guidelines to assist in the management of adult patients with DTC, emphasizing the patient journey beginning with a thyroid cancer diagnosis. Methods: The questions addressed were based, in part, on prior versions of the guidelines, with input from a larger, more diverse complement of stakeholders. The panel included members from multiple specialties involved in thyroid cancer care, including a patient advocate and an expert in systematic reviews/meta-analyses/guidelines who educated and supported task force members. The panel conducted systematic literature reviews to inform the recommendations and commissioned two additional systematic reviews. Published English-language articles were eligible for inclusion, with a final search date of July 1, 2024. A modified Grading of Recommendations Assessment, Development and Evaluation system was used for critical appraisal of evidence and determining the quality of data. The guidelines panel had editorial independence from the ATA. Competing interests of task force members were pre-vetted, regularly updated, communicated with task force members, and assessed and managed by ATA leadership and the Clinical Practice Guidelines and Statements Committee. Results: These revised guidelines begin with the initial cancer diagnosis and continue with recommendations for staging and risk assessment, initial treatment decisions, assessment of treatment responses, monitoring approaches, diagnostic testing, and subsequent therapies based on the strength of evidence for response and consideration of side effects and outcomes. Patient-reported outcomes and identified areas of need for additional high-quality research are highlighted. Conclusions: These revised evidence-based recommendations inform clinical decision-making in the management of DTC that reflect the changing science and optimize the evidence-based clinical care of patients throughout their journey with DTC. Critical areas of need for additional research are highlighted.

Background: Although accumulated experience with lenvatinib in patients with differentiated thyroid cancer (DTC) and progressive radioactive iodine (RAI)-refractory disease has been used to improve management strategies for this disease, findings regarding the actual clinical picture and long-term observation data are insufficient. Methods: We conducted a retrospective cohort study of patients with DTC who received lenvatinib treatment from 2011 to 2022 at the National Cancer Center Hospital East, Japan. The patients were treated under the following treatment and management policies (1) starting dose at 24 mg/day, (2) schedule modification according to individual adverse events status (planned drug holidays), (3) dose escalation of lenvatinib, and (4) local therapy at disease progression, if applicable. This is a retrospective cohort study, although some patients were enrolled in a prospective clinical trial (NCT01321554 and UMIN000022243). Results: Of 91 patients, 59 (64.8%) had papillary carcinoma and 22 (24.2%) had follicular carcinoma. Best overall response in all patients was 60.4% (partial response in 55 and complete response in 0). With a median observation period of 2.9 years (range, 0.1-12.4; interquartile range, 1.7-4.6) under supportive management, including the planned drug holidays (n = 72, 79.1%), dose escalation of lenvatinib at systemic disease progression (n = 21, 23.1%), and local therapy for oligoprogressive disease (n = 11, 12.1%), median progression-free survival and overall survival were 2.4 years (95% confidence interval [CI] 1.9-3.3) and 5.1 years (95% CI 3.3-6.7), respectively. At the time of data cutoff, 19.8% had discontinued lenvatinib treatment due to adverse events, although no adverse event was grade 5. Conclusions: In patients with RAI-refractory DTC treated with lenvatinib, careful treatment optimization and management of adverse events contribute to a favorable, durable prognosis.

Background: Thyroid dysfunction (TD) occurs commonly from immune checkpoint inhibitors (ICI) cancer therapy, but questions remain regarding its predicting factors, appropriate dosing for thyroid hormone replacement, and the strength of association with overall survival (OS). We aim to address these three questions in our study. Methods: We performed a retrospective cohort study of adult patients with cancer who received ICIs from December 1, 2012, to December 31, 2019. After excluding 28 patients with preexisting primary hypothyroidism, 811 patients were evaluated for the development of new-onset ICI-TD. Kaplan-Meier survival and log-rank tests were used to compare OS distributions between ICI-TD status groups, following which Cox regression models addressed immortal time bias (ITB). Results: Of the 811 included patients with a median follow-up of 19.2 months, 122 (15.0%) patients developed ICI-TD. The median age at initiation of ICIs was 64.8 years; women comprised 42.8% of the cohort. There were no significant differences in age, sex, race, malignancy type, or personal history of autoimmunity in patients who developed ICI-TD versus those who did not. ICI-TD occurred most frequently after combination ICI therapy (32%) compared with CTLA-4 ICI and PD-1/PD-L1 ICI monotherapy (p = 0.002). The median levothyroxine dose was the highest, being 1.41 mcg/kg/day in the overt hypothyroidism group. Patients with ICI-TD had a higher median pre-treatment log2(thyrotropin or TSH) level (1.2, corresponding to TSH 2.3 mIU/L) versus those without (0.79, corresponding to TSH 1.7 mIU/L; p = 0.008); however, the area under the curve was <0.6, hence lacking predictive ability. The survival benefit of ICI-TD was not apparent after addressing ITB and adjusting for other variables affecting patient outcomes. Conclusions: The levothyroxine dose needed for overt hypothyroidism from ICI-TD is similar to athyreotic hypothyroidism. While baseline TSH in the upper normal range is associated with an increased risk of ICI-TD, there is no absolute baseline TSH value that accurately predicts ICI-TD in the clinical setting. The link between ICI-TD and OS needs further validation after accounting for ITB.

Background: Thyroid cancer (TC) is infrequently encountered in Birt-Hogg-Dubé (BHD) syndrome. We describe three BHD patients with TC and review the relevant literature. Patient Findings: Patient 1, a 55-year-old male with BHD, developed dedifferentiated oncocytic TC with distant metastases, requiring systemic therapy and radiation. Genetic testing revealed pathogenic variants (PVs) in FLCN, DAXX, and TP53. Patient 2, a 51-year-old female, and her 30-year-old daughter (patient 3) were diagnosed with papillary TC and treated with surgery and radioiodine. Tumor testing in patient 3 demonstrated PV in BRAF (V600E). Gene query analysis (n = 2285 patients) identified 2% FLCN PV prevalence in sporadic TCs, but the prevalence increased to 23% in anaplastic TCs. Literature review revealed 15 TC cases in BHD with diverse clinical presentations. Conclusions: TCs are rare in BHD. FLCN PVs may not be the sole molecular drivers in TCs but may have a substantial role in the development of aggressive TCs.

Background: The management of advanced thyroid cancer has rapidly evolved as several multikinase, and gene-specific inhibitors have substantially improved survival for patients with most types of thyroid cancer. Optimizing management of the treatment-related adverse events (TRAEs) from these medications is important to improve quality of life and outcomes for patients with thyroid cancer. This narrative review discusses common and clinically significant TRAEs of treatments for thyroid cancer and effective management approaches. Summary: Published literature was reviewed to summarize available information on the incidence of TRAEs with medications used to treat thyroid cancer and management approaches for these TRAEs. There are common TRAEs across many treatments for advanced thyroid cancer including fatigue, hypertension, gastrointestinal toxicities, rashes, and hand-foot syndrome. Additionally, several other TRAEs with thyroid cancer treatments are significant because of their frequency with specific medications (e.g., pyrexia syndrome) or their severity (e.g., thromboembolic events and cardiac impairment). Data from clinical trials and real-world data along with expert guidelines and insights from experienced clinicians can guide management approaches for many of these TRAEs. Conclusions: The toxicity profiles are well established for treatments for advanced thyroid cancer, there are evidence-based management approaches for many commonly encountered scenarios. Following these approaches to optimizing management of TRAEs can improve the quality of life and outcomes for patients with thyroid cancer.

Background: Newborn screening for congenital hypothyroidism (CH) has been implemented in high-income countries since the 1970s to prevent intellectual disability. A delayed thyrotropin (TSH) rise with a normal TSH on the first dry blood spot (DBS) sample, followed by an abnormal TSH on the subsequent DBS, is sometimes observed in preterm newborns. The incidence of permanent CH and the screening process in preterm newborns remain controversial. Our aim was to evaluate the incidence of transient and permanent CH and delayed TSH rise in preterm newborns. The utility of a multiple screening samples is discussed. Methods: We conducted a retrospective study on preterm newborns (<37 weeks of gestation) screened at the Newborn Screening Center of Université Libre de Bruxelles between January 2014 and December 2023. A literature review was performed to identify cases of permanent CH with delayed TSH rise in cohorts of preterm newborns. Results: Of the 3578 preterm newborns included in the study, 10 were diagnosed with CH (0.3%). The majority of CH cases were transient (6 out of 10 transient, one deceased and one under ongoing L-thyroxine, too young for weaning attempt). Six cases were detected at the first DBS, four at subsequent DBS. Only two cases were confirmed as permanent CH, yielding an incidence of 1 in 1789 for permanent CH in preterms (0.05%). One of the two had a delayed TSH rise. Genetic testing helped in establishing the diagnosis of permanent CH with gland in situ. Conclusions: Permanent CH appears to be rarer than transient CH among preterm newborns (1/1789 vs. 1/596). Transient CH may be suspected in case of iodine exposure or thyroid ultrasound showing an in situ gland with negative genetic testing and absent maternal blocking antibodies. In such cases, early L-thyroxine weaning may help avoid overtreatment. A delayed TSH rise leading to a false negative first DBS is not uncommon in preterm newborns with permanent CH. This justifies a second DBS in preterms. Given the retrospective nature of this study, these findings should be interpreted with caution, and further prospective research is warranted to confirm these observations.

Background: Thyroid eye disease (TED) is a sight-threatening autoimmune disease with cigarette smoking as one of the key risk factors. Cigarette smoking affects both the severity of TED and the patient's response to medication. However, the underlying pathogenic mechanisms of smoking in TED remain unclear. Methods: Orbital fibroblasts (OFs) were extracted from patients with TED and non-TED controls, and treated with cigarette smoking extract (CSE). Luminex assays and Western blots were employed to examine inflammatory status and pathological phenotypes of OFs. A specific reactive oxygen species (ROS) probe was used to evaluate oxidative stress levels. RNA-sequencing of CSE-treated OFs was used to analyze differentially expressed genes. Immunofluorescence and RNA-sequencing were used to examine the expression of receptor for advanced glycation end products (RAGE) signaling molecules in patients. Small interfering RNA sequences and a RAGE-specific inhibitor were employed to investigate the effects of RAGE blockade on cigarette smoking-related pathological phenotypes. To validate our findings in vivo, we generated an adenovirus-induced TED mouse model with exposure to cigarette smoke. Results: Exposure to CSE resulted in an inflammatory phenotype of OFs together with higher levels of oxidative stress. OFs exposed to CSE presented susceptibility to transforming growth factor-β-induced myofibroblast differentiation, and 15-D-PGJ₂-induced adipocyte differentiation, indicating pro-fibrotic and pro-adipogenic phenotypes. RNA-sequencing of CSE-treated OFs revealed upregulation of RAGE signaling molecules. TED patients with smoking history also exhibited higher levels of RAGE signaling, both in the orbit and peripheral blood, compared with non-smoking patients. Enhancement of inflammatory status was associated with activation of the ROS-nuclear factor-kappa B pathway downstream of RAGE. RAGE gene interference or administration of RAGE inhibitor effectively mitigated cigarette smoking-related pathological changes in OFs. Disrupting RAGE signaling in TED mice efficiently ameliorated smoking-induced disease progression in vivo. Conclusions: Cigarette smoking-relevant TED progression was linked with RAGE signaling activation, leading to the exacerbation of orbital inflammation and tissue-remodeling, including fibrosis and adipogenesis. Our findings demonstrate that cigarette smoke exposure affects the biological characteristics of TED-derived OFs and supports RAGE as a promising therapeutic target for the management of patients with TED and smoking habits.