European Thyroid Journal最新文献

Objective: To establish thyroid ultrasound volume norms appropriate for studies of diffuse goiter in a cohort of children and adolescents from an iodine-deficient population exposed to 131I by the Chernobyl fallout.

Methods: A cohort of 11,970 Belarusians aged ≤18 years at the time of the 1986 Chernobyl accident with individual thyroid radiation dose estimates was screened 10-18 years later. From these, a low-dose subset of 2,392 with no thyroid diseases was selected to construct age- and sex-specific normative values for thyroid ultrasound volume, compared to Belarusian Ministry of Health (MOH) norms and existing WHO and European standards.

Results: Cohort-specific values were generally lower than MOH norms and WHO standards for 11-17-year-olds. For those aged ≥18 years, internal norms were 30% higher in males and 15-30% lower in females than MOH norms, and exceeded European values for both sexes. Thyroid volume norms were about 40% higher in males and 30% higher in females as a function of BSA compared to European values. Thyroid volume continued to increase in both sexes, and by age 30-34 years, cohort-specific norms were 6% higher in males and 26% higher in females than European values. Urinary iodine concentration did not significantly explain variance in thyroid volume beyond sex, age, and BSA.

Conclusions: In this iodine-deficient cohort of young Belarusians exposed to 131I by Chernobyl fallout, thyroid ultrasound volumes differed substantially from MOH norms and established WHO standards, prompting a revision of diffuse goiter definition using cohort-specific normative values.

Background: Healthcare claims data are increasingly used to investigate the epidemiology of benign thyroid diseases. Here, we estimate the prevalence of treated hyper- and hypo-thyroidism and assess the potential sociodemographic and geographic disparities in France in 2020, given the country's poor epidemiological knowledge of these conditions.

Methods: We used the French national healthcare data system, which covers nearly the entire population residing in France (over 67 million inhabitants in metropolitan and overseas departments). Prevalent cases were identified based on patients' long-term disease status, hospitalisation for hyper- and hypo-thyroidism and reimbursements for thyroid hormones, antithyroid drugs, iodine-131 and thyroid surgery. Thyroid-stimulating hormone, antithyroid antibodies and previous therapy for thyroid cancer and hyperthyroidism were considered to characterise the origin and surveillance of hypothyroidism.

Results: In 2020, we identified 112,992 and 2,986,333 cases of treated hyper- and hypo-thyroidism, respectively, with an overall prevalence of 0.17 and 4.45 per 100 inhabitants. Marked differences were observed in terms of sex, age group and geographic area (department) for both conditions and deprivation level of the place of residence for hyperthyroidism only. The proportion of hypothyroidism following previous therapy for thyroid cancer or hyperthyroidism was less than 10%. Adequate monitoring (thyroid-stimulating hormone checked in the past year) occurred in 73.7% of hypothyroid subjects, with large variations across departments.

Conclusions: This study provides prevalence estimates of treated hyper- and hypo-thyroidism at the national and departmental levels in France and improves epidemiological knowledge of both conditions. It also supports using healthcare claims data for their epidemiological surveillance.

Objective: Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease without a cure. Mesenchymal stem cells (MSCs) may offer the opportunity to improve autoimmune thyroiditis.

Methods: We replicated the pathogenic factors of HT and established a stable autoimmune thyroiditis model in NOD.H-2h4 mice by administering iodine for 12 weeks. We used orthotopic injection to transplant bone MSCs (BMSCs) into the thyroid. Immunohistochemistry, enzyme-linked immunosorbent assay, flow cytometry, and hematoxylin and eosin and immunofluorescence staining were used to evaluate the effects of cell transplantation.

Results: Orthotopic BMSC transplantation decreased serum thyroglobulin antibody and caspase 3 levels; increased proliferating cell nuclear antigen levels; decreased CD4+/CD3+ T cells, Th1/Th2, and Th17/Treg ratios; decreased TNF-alpha (a proinflammatory cytokine) and interferon-gamma levels; and increased transforming growth factor-beta and interleukin-10 levels. In addition, it increased CD90/S100A4 and CD90/TTF-1 co-expression.

Conclusion: Orthotopic BMSC transplantation improved the inflammatory environment by regulating the secretion of anti-inflammatory cytokines, promoting regeneration, and reducing apoptosis in the thyroid tissue. Bone marrow-derived stem cells inhibited T cell activation, maintained a balance between T cell subpopulation ratios, and halted thyroiditis progression. Finally, transplanted BMSCs could transform into fibroblasts and thyroid cells. This study elucidated the pathogenesis of HT and provided evidence supporting the potential of MSCs in HT treatments.

Autoimmune thyroid disease (AITD) is the most prevalent organ-specific autoimmune condition, encompassing Graves' disease (typically linked with hyperthyroidism) and Hashimoto's thyroiditis (generally associated with hypothyroidism). The growing body of evidence suggests that AITD can interfere with brain function. Here, we review the impact of AITD on cognition, mood, and psychiatric disorders by analysing data from clinical, animal, ex vivo and in vitro studies to reveal the molecular mechanisms by which AITD affects brain function. Most reports indicate a stronger association between cognitive impairments and hyperthyroidism (including AITD-related) than hypothyroidism. Both hypothyroidism and hyperthyroidism are linked with a higher risk of depression. At least some of those effects can be mediated by altered concentrations of T3 (3,3',5-triiodo-L-thyronine), which regulates gene expression in the brain microenvironment, affecting neurogenesis, angiogenesis, neurotransmitter release, and synaptic transmission. Diminished TSH (thyrotropin) signalling may also impair learning and memory by inhibiting the Wnt5a-β-catenin pathway. Thyroid disorders may also contribute to neurodegeneration by T3-mediated attenuation of amyloid-β elimination or TRH-induced formation of neurofibrillary tangles. Surprisingly, most clinical studies do not specify the immune origin of hypothyroidism or hyperthyroidism, therefore further studies involving large, well-characterised patient cohorts are needed to clarify the relationships between AITD and cognitive impairments and psychiatric disorders. Furthermore, data on the effect of anti-thyroid antibodies on brain function are scarce and inconclusive. Given the association between hyperthyroidism and an increased risk of dementia, cognitive impairment and mood disorders, adequate treatment and careful monitoring of AITD patients are essential to prevent the induction of exogenous hyperthyroidism.

Objective: Graves' disease increases metabolism and leads to net lipid degradation. Circulating acylcarnitines reflect lipid metabolism and the state of fatty acid oxidation in individuals. The aim of this study was to explore the lipid and acylcarnitine profiles in patients with Graves' disease.

Methods: Seven lipids/apolipoproteins and 23 acylcarnitines were analysed in 100 newly diagnosed Graves' disease patients and validated in another 51 patients. Both groups were age- and sex-matched with healthy subjects.

Results: The hyperthyroid Graves' disease patients (n = 88) from the main cohort (78 females, median age 42 (17-67) years) had significantly (P < 0.05) higher levels of medium- and long-chain acylcarnitines, and lower levels of short-chain acylcarnitines, compared with healthy subjects. Factor analysis showed that medium- and long-chain acylcarnitines explained most of the differences between the two groups. Serum levels of the five lipids/apolipoproteins were significantly lower in the hyperthyroid Graves' disease patients compared with healthy subjects. Patients (n = 21) treated with antithyroid drugs for 6 weeks had acylcarnitine levels closer to healthy subjects, compared with 79 treatment-naïve hyperthyroid patients. The main findings were confirmed in the validation group.

Conclusion: Increased levels of medium- and long-chain acylcarnitines in patients with newly diagnosed Graves' disease may reflect accelerated catabolism. Lower levels of short-chain acylcarnitines point to Graves' disease being a catabolic condition, with a shift in energy source from carbohydrates to fat.

Objective: Treatment for distant metastases (DM) of differentiated thyroid cancer (DTC) aims to improve the prognosis and quality of life (QOL). Radioactive iodine and molecular targeted therapies are the primary systemic treatments for DM. Combining these with local treatments, such as surgery and radiotherapy targeting metastatic sites, may provide additional benefits to systemic therapy.

Methods: This study reviewed the additional effects of local therapies on common metastatic sites of DTC, such as pulmonary or bone metastases (BM), the efficacy of bone-modifying agents (BMAs) for BM, and the therapeutic effects of local treatments for less common brain metastases.

Results: Although based on retrospective studies with no definitive conclusions on the effectiveness of each treatment, local therapy for DM in DTC patients has been shown to enhance prognosis and QOL in several studies. Considering the results of clinical trials for metastatic tumors, local therapy for one or a few pulmonary or BM in DTC should be considered, if expected to improve prognosis and QOL. Surgical intervention is recommended for spinal metastases presenting with spinal compression symptoms or for long BM in extremities at risk of pathological or impending fractures. BMAs are also recommended to reduce the risk of skeletal-related events. Surgery, stereotactic radiotherapy, and whole-brain radiotherapy are suggested for brain metastases to improve the prognosis and QOL.

Conclusion: Incorporating local therapy alongside systemic treatment can enhance the prognosis and QOL and should be considered a viable treatment option.

Alemtuzumab is a powerful anti-CD52 drug that is an established treatment option in patients with multiple sclerosis due to its proven efficacy. However, in about 50% of patients, the use of alemtuzumab is burdened by the development of secondary autoimmune thyroid diseases, constituting a range of alemtuzumab-induced autoimmune thyroid diseases (AIATDs). Graves' disease (GD) is the most common AIATD, with an incidence of approximately 60%, and presents different characteristics from the conventional form. Indeed, GD with a fluctuating course is significantly more prevalent (15-50%), which poses a major challenge for physicians in its management. Other AIATDs also exhibit distinct features compared to their conventional counterparts; notably, hypothyroidism is frequently associated with TSH-receptor blocking antibodies, and alemtuzumab-induced GD demonstrates a higher rate of fluctuating course and potential for spontaneous remission. Alemtuzumab-induced thyroid eye disease (TED) is less common than conventional TED, with similar clinical and management characteristics. In this review, we summarize the latest evidence, also from real-world studies, with a focus on clinical management and possible predictors of AIATDs.

Introduction: Mutations of RAS genes are detected in a spectrum of follicular-patterned thyroid tumors. Preoperative prediction of invasive cancers based on the presence of RAS mutation alone is challenging because non-invasive and invasive tumors tend to have similar sonographic and cytologic features. The aim of this study was to perform clinicopathologic and molecular analyses of RAS-mutant tumors, identify molecular and clinical markers associated with invasiveness, and determine their diagnostic and therapeutic potentials.

Methods: We collected clinicopathologic characteristics and performed RNA-seq on 48 surgically resected RAS-mutant thyroid tumors (23 non-invasive and 25 invasive). A classifier using expression data of selected invasiveness markers and clinical parameters was applied to an independent set of 54 RAS-mutant fine-needle aspiration (FNA) samples to predict invasion. Selected markers were investigated in vitro and in vivo.

Results: On RNA-seq analysis, invasive RAS-mutant tumors showed different gene expression profiles compared to non-invasive tumors. Expression levels of six selected genes (CA12, CD44, LRP4, ECM1, FN1, and CRABP1) were associated with invasiveness on qRT-PCR. Expression levels of these genes plus nodule size predicted invasion in RAS-mutant FNA samples with 95% sensitivity and 89% specificity. siRNA silencing and chemical inhibition of CA12 reduced invasion of RAS-mutant human thyroid cells. Treatment of RAS-mutant xenografts with CA12 inhibitors arrested tumor growth.

Conclusions: Development of invasion in RAS-mutant tumors is associated with significant alteration in gene expression. Expression levels of six genes and nodule size may predict invasion in RAS-mutant thyroid nodules, whereas chemical inhibition of CA12 may have a potential therapeutic effect in RAS-mutant tumors.