European Thyroid Journal最新文献

Objective The final surgical pathology report follows the patient throughout their cancer journey. For locoregionally advanced cancers, lack of surgeon-pathologist communication can lead to understaging, adversely impacting management. Our study aims to improve the accuracy of staging grossly invasive thyroid cancer by introducing an anatomic checklist, enhancing surgeon-pathologist communication. Methods We studied 35 consecutive patients with either gross extrathyroidal or extranodal extension, 29 of whom underwent primary resections requiring AJCC staging. Surgeon A initially only dictated an operative report. Surgeon B transmitted an anatomic checklist to the pathologist in addition to the standard operative note. Final pathology reports were reviewed for AJCC staging accuracy. Surgeon A transitioned to submission of an anatomic checklist for his final 6 cases. Results 13 of the 14 final pathology reports without a checklist, were understaged. All 15 cases with a surgeon completed anatomic checklist were accurately staged. There was a statistically significant improvement in the accuracy of staging reported in the final pathology reports when an anatomic checklist was submitted as compared to when it was not (p<0.01, Fisher exact test, two-tailed). All of the final pathology reports for recurrent cases without a checklist failed to define anatomic parts that were resected. The time to complete the checklist was less than 90 seconds. Conclusion A surgeon completed anatomic checklist allows pathologists to more accurately stage grossly invasive thyroid cancers. This rapidly completed form eliminates the need for a pathologist to analyze the operative note and facilitates both risk of recurrence and AJCC determination.

Background: Congenital hypothyroidism (CH) is a preventable cause of neurodevelopmental delay in children, detectable by newborn screening (NBS) programs for CH. Since NBS for CH was started in Canada in 1974, numerous countries have successfully implemented this public health strategy. However, in 2014, only 29.3% of newborns worldwide were screened by NBS for CH.

Objective: This study aimed to assess the implementation of new NBS programs for CH over the past decade, and screening methods and coverage rates of current programs. In addition, it sought to update the worldwide iodine status.

Methods: We reviewed literature data on NBS programs for CH and their coverage rates for each country, using PubMed, Embase and Google searches.

Results: Currently, 29.6% of children worldwide are screened for CH. Europe, North America, Oceania, China, Japan and Israel have efficient programs with optimal coverage. Recently, some countries of Central and Western Asia have implemented NBS programs for CH, and coverage has increased in several Asian countries. South America has also seen substantial improvements in coverage. In contrast, almost none of the African countries has widespread screening programs, but some attempts with pilot studies and local initiatives have been witnessed. Global iodine sufficiency has improved, with 149 of 193 countries achieving adequate iodine levels by 2023.

Conclusions: Over the past decades, several countries have launched NBS programs for CH or conducted pilot studies, and the coverage of most existing NBS programs has increased. Nevertheless, approximately 70% of newborns worldwide still lack access to NBS for CH, predominantly in African and Asian countries, accounting for a significant part of annual births.

Objective: Pleural metastasis (PM) is rare in patients with differentiated thyroid cancer (DTC). Radioiodine (131I) therapy has been the main treatment for postoperative metastasis and recurrence of DTC. However, clinical data on PM from DTC are limited. This study investigated the clinicopathological characteristics of patients with PM from DTC that were treated surgically and with 131I therapy and evaluated their long-term prognosis and prognostic factors.

Methods: A review of the Shanghai Sixth People's Hospital medical records from 2010 to 2023 identified PM in 27 of 14,473 patients with DTC. Overall survival (OS) was assessed by the Kaplan-Meier method.

Results: The prevalence of PM in DTC was 1.87‰ (27/14,473). The median age at the time of initial diagnosis of PM was 59 years (range: 34-79). At the end of follow-up, eight patients (29.63%) had disease progression (PD), four (14.81%) had a partial response, and the remainder had stable disease; no patient achieved complete response. Twelve patients (44.44%) died, and 15 (55.56%) survived. Thirteen patients (48.15%) did not show 131I avidity, and 16 (59.26%) had radioiodine-refractory DTC (RR-DTC). Twenty patients (74.07%) had malignant pleural effusion (MPE), which was large in 11 cases (40.74%) and moderate in two. More-than-moderate MPE (P = 0.031), lack of 131I avidity (P = 0.041) and RR-DTC (P = 0.030) were significantly associated with worse 5-year OS in patients with PM of DTC.

Conclusions: PM is rare in DTC. Lack of 131I avidity, RR-DTC and more-than-moderate MPE are associated with poor OS in patients with DTC and PM.

Immune checkpoint inhibitors (ICIs) frequently cause immune-related adverse events (irAEs), with thyroid irAEs being the most common endocrine-related irAEs. The incidence of overt thyroid irAEs was in the range of 8.9-22.2% in real-world settings, typically triggered by antibodies against PD-1 and PD-L1 and rarely by anti-CTLA-4 antibodies alone. The representative clinical course involves biphasic changes in thyroid function: transient thyrotoxicosis and subsequent persistent hypothyroidism. The identified risk factors for thyroid irAEs include the presence of thyroid autoantibodies, thyroid uptake on 18F-FDG-PET, prior use of tyrosine kinase inhibitors (TKIs), high BMI and high thyroid-stimulating hormone levels. There is evidence that overt thyroid irAEs are associated with good prognosis, at least in non-small cell lung cancer. Although the clinical features have been well clarified, the management strategies require further refinement. Routine monitoring of thyroid function every 4-6 weeks during ICI therapy is recommended for early detection of thyroid irAEs. While thyrotoxicosis generally requires observation only, hypothyroidism should be promptly treated with levothyroxine replacement. Continuation of ICI therapy is typically feasible in patients with thyroid irAEs, provided their overall health remains stable. However, these strategies were largely based on clinical experience with monotherapy. As combination ICI therapies have been developed as first-line treatments, antitumor agents may modify the clinical features of thyroid irAEs. For example, cytotoxic agents can delay the onset of thyroid irAEs, while TKIs are often linked to early-onset hypothyroidism, independent of ICI use. Given the increasing diversity and complexity of cancer immunotherapy, it is essential to vigilantly screen for thyroid irAEs.

Deletion of the long q arm of chromosome 22 (22qDEL) is the most frequently identified recurrent somatic copy number alteration observed in papillary thyroid carcinoma (PTC). Since its role in PTC is not fully understood, we conducted a pooled analysis of genomic characteristics and clinical correlates in 1094 primary tumors from four published PTC genomic studies. The majority of PTC cases with 22qDEL exhibited arm-level loss of heterozygosity (86%); nearly all PTC cases with 22qDEL had losses in 22q12 and 13, which together constitute 70% of the q arm. Our analysis confirmed that 22qDEL occurs more frequently with RAS point mutations (50.4%), particularly HRAS (70.3%), compared with other PTC drivers (9.3%), supporting the conclusion that 22qDEL is unlikely to be a solitary driver of PTC but possibly an important co-factor in carcinogenesis, particularly in PTCs with RAS driver mutations. Differential RNA expression analyses revealed downregulation of most genes located on chromosome 22 in cases with 22qDEL compared to those without 22qDEL. Many differentially expressed genes are drawn from immune response and regulation pathways. These findings highlight the value of further investigations into the contributions of 22qDEL events to PTC, perhaps mediated through immune perturbations.

Objective: Fine-needle aspiration (FNA) cytological analysis fails to confirm the benignity or malignancy of Bethesda III, IV and V thyroid nodules. Molecular tests performed on FNA samples have demonstrated interesting results in improving the diagnosis of these nodules. The aim of this study was to assess the performance of a large next-generation sequencing (NGS) panel in thyroid nodules with indeterminate cytology (Bethesda III, IV and V).

Methods: Retrospective, monocentric study including 121 patients with cytologically indeterminate thyroid nodules (Bethesda III, IV and V) who underwent a routine FNA procedure for molecular testing using the AmpliSeq general cancer NGS panel, with an available final histological diagnosis. The main objective was to estimate the negative predictive value (NPV) of malignancy of the AmpliSeq panel in Bethesda III and IV thyroid nodules. Performance assessment (sensitivity, specificity, positive predictive value (PPV) and NPV) was carried out in the grouped categories III and IV, in the overall cohort and in each Bethesda category. The final histological diagnosis was used as the designated gold standard.

Results: Histologically, 86 nodules were benign and 35 nodules were malignant. Molecular analysis yielded a positive result in 40 nodules. Panel performances assessed in the grouped categories Bethesda III and IV demonstrated a 55.0% (95% CI: 31.5; 76.9) sensitivity, a 76.9% (95% CI: 66.0; 85.7) specificity, a 37.9% (95% CI: 25.7; 51.9) PPV and an 87.0% (95% CI: 80.2; 91.7) NPV, considering a 20% prevalence of malignancy.

Conclusions: The performances of the AmpliSeq panel are promising; however, the NPV is not sufficient to avoid diagnostic surgery in cytologically indeterminate thyroid nodules.

Significance statement: Different ancillary molecular tests have been marketed in the USA and are integrated into the management of thyroid nodules with indeterminate cytology. Unfortunately, none of these molecular tests are currently available in France and clinicians lack effective tools for the management of these nodules. The aim of this work was to assess the performance of a large general-cancer targeted NGS panel in a series of thyroid nodules with indeterminate cytology (i.e. Bethesda III and IV categories and, to some extent, the Bethesda V category), managed in a French university medical center referral for thyroid tumors.

Background: Adiposity may be associated with thyroid nodularity. However, its impact on the number of nodules and the risk of malignancy is unclear.

Aim: To evaluate the impact of adiposity on thyroid nodules using body mass index (BMI), ultrasonographic (US) data and cytological data.

Methods: A retrospective cohort study of 310 patients with thyroid nodules was performed. Patients were categorized based on their BMI, and grayscale US data and fine-needle aspiration cytology results were evaluated.

Results: Patients with BMI ≥ 25 kg/m2 were found to have a higher number of thyroid nodules compared to those with BMI < 25 kg/m2 (4.25 ± 2.42 vs 3.66 ± 1.93) (P value = 0.05). Patients with BMI ≥ 25 kg/m2 had more suspicious and malignant cytology than those with BMI < 25 kg/m2 (P value = 0.029). Patients with BMI ≥ 25 kg/m2 had more nodules with intermediate and high suspicion sonographic patterns. However, this did not reach statistical significance.

Conclusion: Overweight and obese patients have a trend for more thyroid nodules and have a higher risk of being diagnosed with thyroid malignancy.

Objective: Active surveillance (AS) has emerged as a viable alternative to immediate surgery for low-risk thyroid cancer. However, several barriers still hinder its widespread adoption and implementation by physicians.

Methods: In 2024, an email survey was conducted among members of the Korea Thyroid Association to assess their perspectives on AS. The survey comprised questions about clinical case scenarios, perceptions of the benefits and risks associated with AS, factors influencing the consideration of AS and unmet needs for the implementation of AS.

Results: Among the 287 physicians surveyed, 40.8% were endocrinologists, followed by general surgeons at 20.9% and otolaryngologists at 19.9%. The majority worked in tertiary hospitals and had over 10 years of experience. Regarding a 65-year-old man with a 0.7 cm low-risk thyroid cancer, 74.6% of the respondents considered AS. Endocrinologists and physicians with higher self-assessment and experience explaining AS to patients were more inclined to consider AS. Although the respondents recognized the benefits of AS, such as avoiding surgery and reducing surgical complications, they expressed concerns about potential risks, including the possibility of patient lawsuits due to disease progression and patient worry and anxiety about the disease. Challenges in screening candidates for AS were highlighted, especially in detecting recurrent laryngeal nerve involvement and lymph node metastases. Additionally, physicians noted unmet needs in AS implementation, specifically regarding psychological support for patients and reimbursement for long-term follow-up costs.

Conclusions: The survey underscored the need for further research and initiatives to overcome the barriers and implement AS for the management of low-risk thyroid cancer.

Aims: Thyroid eye disease (TED) is an autoimmune orbital disorder that diminishes the quality of life (QOL) in affected individuals. Graves' ophthalmopathy (GO)-QOL questionnaire effectively assesses TED's effect on patients. This study aims to investigate the factors influencing visual functioning (QOL-VF) and physical appearance (QOL-AP) scores in Chinese TED patients using innovative data analysis methods.

Methods: This cross-sectional study included 211 TED patients whose initial visit to our clinic was from July 2022 to March 2023. Patients with previous ophthalmic surgery or concurrent severe diseases were excluded. GO-QOL questionnaires, detailed medical histories and clinical examinations were collected. The distribution of GO-QOL scores was analyzed, and linear regression and machine learning algorithms were utilized.

Results: The median QOL-VF and QOL-AP scores were 64.29 and 62.5, respectively. Multivariate linear regression analysis revealed age (P = 0.013), ocular motility pain (P = 0.012), vertical strabismus (P < 0.001) and diplopia scores as significant predictors for QOL-VF. For QOL-AP, gender (P = 0.013) and clinical activity (P = 0.086) were significant. The XGBoost model demonstrated superior performance, with an R2 of 0.872 and a root mean square error of 11.083. Shapley additive explanations (SHAP) analysis highlighted the importance of vertical strabismus, diplopia score and age in influencing QOL-VF and age, clinical activity and sex in QOL-AP.

Conclusion: TED significantly affects patient QOL. The study highlights the efficacy of XGBoost and SHAP analyses in identifying key factors influencing the QOL in TED patients. Identifying effective interventions and considering specific demographic characteristics are essential to improving the QOL of patients with TED.

Background: Pituitary lesions after traumatic brain injury (TBI) are frequent in children and adolescents, but the rate of post-TBI central hypothyroidism remains uncertain.

Objective: To identify the long-term incidence of post-TBI CH and the clinical and laboratory characteristics of this complication in children and adolescents.

Methods: The analysis included 31 patients with a history of TBI with at least 1 year of follow-up. Patients were evaluated at hospital admission and every 3 months thereafter. Assessments included clinical evaluation, brain CT and hormone assessments (basal fT4, IGF-1, cortisol and adrenocorticotropic hormone; insulin tolerance test/thyrotropin-releasing hormone test with TSH, growth hormone and cortisol measurement; and corticotropin-releasing hormone test, if indicated). The CH diagnosis was based on clinical and laboratory findings and a therapeutic trial with levothyroxine.

Results: Overall, five patients (16%) developed CH (3 with associated adrenal insufficiency). At 3 and 12 months, median fT4 values were lower in patients with CH compared with those without anterior pituitary dysfunction (n = 18; P = 0.01). Patients with CH received levothyroxine and progressed with clinical resolution and increased median fT4 (from 0.92 to 1.47 ng/dL) and IGF-1 (from -2.08 to -0.22 standard deviation scores (SDS)) levels. Temporary suspension of levothyroxine was accompanied by decreased median fT4 (1.02 ng/dL) and IGF-1 (-1.07 SDS) levels and reappearance of clinical symptoms, which resolved once levothyroxine was reinitiated.

Conclusions: The longer follow-up, valorization of clinical manifestations, nontraditional laboratory approach and therapeutic trial with levothyroxine in the present study revealed a higher rate of post-TBI CH in children and adolescents than that reported in the literature.