European Thyroid Journal最新文献

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.

Objective: The prevalence of Thyroid-Cancer (TC) has increased worldwide and an association with metabolic and cardio-vascular disorders has been reported. Moreover, an increasing percentage of patients are currently diagnosed incidentally through non-thyroid related imaging for other clinical conditions. Our aim was to assess the prevalence of Thyroid-Related (TD) versus Incidental (ID) pre-surgery reasons leading to TC diagnosis and to compare the two groups in terms of clinical characteristics, size and severity of TC at presentation and rate of non-thyroid cancers and cardiovascular/metabolic comorbidities.

Design: we performed a retrospective cohort study in three high-volume hospital-based centers for thyroid diseases (Pavia, Latina and Messina) in Italy.

Patients: Consecutive patients with TC Measurements: data on pre-surgery reasons leading to TC diagnosis, age, sex, BMI, presence of cardio-metabolic comorbidities and non-thyroid cancer.

Results: among the 327 enrolled subjects the diagnosis of TC was prompted by thyroid-related reasons in 262 (80.1%, TD group) and incidental in 65 (19.9%, ID group). The ID group patients were more frequently males, significantly older and with a higher BMI than the TD group ones, they had a higher rate of non-thyroidal cancers and cardiovascular/metabolic comorbidities. No significant differences could be observed in terms of TC histotype, cancer size, extra-thyroidal extension, lymph-node metastases, AJCC Staging or ATA Risk stratification.

Conclusions: biological features of TC are similar in the TD and ID groups, but patients in the two groups display significant differences regarding their clinical features.

In recent years, germline mutations in the microRNA (miRNA) processor genes DICER1 and DGCR8 have been coupled to the development of thyroid follicular nodular disease (TFND), thereby casting new light on the etiology of this enigmatic, benign condition in non-iodine-deficient regions. Moreover, DICER1 and DGCR8 mutations have also been reported in rare subsets of follicular cell-derived thyroid carcinomas. Specifically, truncating germline or missense somatic DICER1 mutations have been reported in small subsets of pediatric and adolescent follicular thyroid carcinoma (FTC) and poorly differentiated thyroid carcinoma (PDTC). Similarly, a recurrent somatic mutation of the DGCR8 gene has been observed in highly aggressive FTCs and in some indolent cases of encapsulated follicular variant of papillary thyroid carcinoma. The reason why identical mutations in the same miRNA processor gene can lead to such a myriad of thyroid conditions, ranging from benign TFND to FTCs and PDTCs, remains unclear. This review highlights key features of miRNA regulator gene mutations in thyroid disease and explores their potential roles as drivers or progression events in tumor development.

Background: Thyroid hormones and sympathetic stimulation are needed for activating Brown adipose tissue (BAT) during cold exposure. Studies of human cold exposure have demonstrated both increased production and raised clearance of triiodothyronine (T3). Greenlandic hunters provide a unique model for evaluating metabolic effects of cold exposure.

Aim: We aimed to explore the dynamics of thyroid hormones when blocking sympathetic activity in Greenlandic hunters during winter to inspire knowledge on mechanisms of BAT activation.

Methods: We conducted a 7-day field study of Greenlandic hunters (n=7) in East Greenland in February. The sympathetic system was blocked using a non-selective beta blocker for seven consecutive days. A group of non-hunter Greenlanders (n = 8) from the same settlement were included for parallel sampling. All participants were healthy men. Blood samples were drawn daily for measurement of TSH, thyroid hormone levels, and thyroglobulin.

Results: Hunters had higher serum thyroglobulin, TSH, and high fT3/fT4 ratio compared to controls. Blocking the sympathetic activity was followed by changes in serum thyroglobulin and fT3 with an initial decrease and subsequent restoration of levels, while TSH and fT4 showed a gradual increase over the course of the study. The fT3/fT4 ratio showed a continuous and marked decrease.

Conclusion: We hypothesise that when blocking the sympathetic system, TSH increases to uphold the production of T3 needed for maintaining BAT activity. Additionally, alterations of fT3/fT4-ratio support a hypothesis of adrenergic stimulation promoting T3 over T4 secretion from the thyroid via the adrenergic nerve terminals in the thyroid.

Background: Thyroglobulin (Tg) is a biomarker of iodine status. Newborn Tg is a more sensitive marker than neonatal TSH in detecting variations in iodine intake. This study aims to validate an enzyme-linked immunosorbent assay (ELISA) for Tg determination on dried blood spots (DBS) in newborns. This study also sets out to assess the stability of Tg and the influence of newborns' hematocrit on Tg determination.

Methods: A commercially available ELISA Tg assay was adapted for use on DBS. DBS-Tg in cord blood was measured in 209 newborns delivered from healthy euthyroid pregnant women. Sensitivity, linearity, repeatability, and intermediate fidelity were determined using the appropriate standards and quality control materials.

Results: The limit of detection of the DBS-Tg assay was 2.4 µg/L, and the limit of quantification was 5.8 µg/L. Repeatability and intermediate fidelity were 7.7-8.3% and 11.0-11.2%, respectively. The median cord plasma Tg and DBS-Tg values in newborns were not significantly different, 30.2 (21.3-44.4) µg/L and 31.6 (19.3-48.7) µg/L (P = 0.48) with the ELISA, respectively, and 76.5 (40.0-101.5) µg/L with the Elecsys assay with an R = 0.88. DBS-Tg concentrations decrease with increasing hematocrit values (P < 0.05). DBS-Tg values were stable at a concentration of 25 µg/L for 12 months at -20ºC and 4ºC.

Conclusion: This DBS-Tg assay demonstrated good analytical performance over a wide range of Tg concentrations, suggesting it is well suited to detecting variations in Tg concentrations. Studies comparing populations with different prevalence of anemia should consider the effect of hematocrit on DBS-Tg determination. The availability of a DBS-Tg assay for newborns makes it possible to integrate iodine status monitoring with newborn screening for inherited metabolic diseases.

Patients with an inactive thyroid hormone (TH) transporter MCT8 (Allan-Herndon-Dudley Syndrome, AHDS) display severe neurological impairments and motor disabilities, indicating an indispensable function of MCT8 in facilitating TH access to the human brain. Consequently, the CNS of AHDS patients appears to be in a TH deficient state, which greatly compromises proper neural development and function. Another hallmark of this disease is that patients exhibit elevated serum T3 levels, leading to a hyperthyroid situation in peripheral tissues. Several treatment strategies have been developed and evaluated in preclinical mouse models as well as in patients. Here, we discuss these different therapeutic approaches to overcome MCT8 deficiency and summarize the current achievements and challenges in improving brain maturation in the absence of MCT8.

Objective: Poorly differentiated thyroid carcinomas (PDTCs) are rare and aggressive head and neck malignancies with a poor prognosis. Systemic treatment for incurable PDTC consists of multi-kinase inhibitors (MKIs) based on extrapolation from the experience with radioiodine refractory differentiated thyroid cancer (DTC). Cabozantinib is an approved second-line MKI therapy for DTC, but there are limited data regarding the safety and efficacy of cabozantinib for PDTC.

Methods: We conducted a single-institution, retrospective analysis of patients with PDTC who received cabozantinib in any line of therapy. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record. Median progression-free survival (PFS) and overall survival (OS) were primary endpoints and estimated using Kaplan-Meier methodology.

Results: Seven patients with PDTC who received cabozantinib were included. 4/7 (57%) patients had a partial response to cabozantinib, while 2/7 (29%) had stable disease (SD) as their best response. The median time on treatment for cabozantinib was 10.53 months. The median PFS from the start of cabozantinib was 12.9 months, and median OS was 14.21 months. Most adverse events to treatment (5/6) were low grade. Two (29%) patients were alive at the date of the last follow-up.

Conclusion: Cabozantinib is an effective and reasonably well-tolerated treatment option for patients with PDTC. Prospective studies are needed to further investigate the role of cabozantinib in the treatment of PDTC, alone and in combination with other agents, including checkpoint inhibitors.