BackgroundThe sodium-iodide symporter (NIS), encoded by the SLC5A5 gene, is essential for iodide uptake and the effectiveness of radioiodide therapy in differentiated thyroid carcinoma (DTC). Data addressing the relationship between NIS transcription and protein expression in pediatric DTC remain limited.MethodsWe conducted a retrospective cohort study of pediatric and adolescent patients with DTC, evaluating NIS protein expression by immunohistochemistry in tumor and adjacent nontumoral thyroid tissues and tumor SLC5A5 mRNA expression by quantitative real-time PCR. Clinical, pathological, molecular, and treatment-related variables were analyzed.ResultsWe analyzed DTC samples from 92 patients diagnosed under the age of 19. NIS was present at significantly lower levels in tumor cells than in adjacent nontumoral cells (odds ratio (OR): 106.8; 95% (CI): 30.7–337.5; P < 0.0001). NIS was only detected in 20/92 of tumor samples, while SLC5A5 was expressed in 36/70 of tumor samples. No associations were found between NIS expression or SLC5A5 expression and clinical or histological features, metastasis, iodide-131 (I-131) activity, or treatment response. A dissociation between gene expression and protein detection was observed. Despite reduced tumoral NIS protein expression, most patients achieved an excellent response to radioiodide therapy.ConclusionThis study highlights significant differences in NIS expression between pediatric thyroid tumors and adjacent nontumoral tissue, with a lower proportion of NIS-positive tumors compared with SLC5A5-high cases. No associations were observed between NIS protein detection or SLC5A5 expression and clinical features, histology, tumor aggressiveness, or treatment response.

The heterogeneity of extraocular muscles (EOMs) in thyroid eye disease (TED) correlates with response to intravenous glucocorticoid (IVGC) therapy but remains unquantified by current imaging. This study applied habitat imaging to characterize EOM heterogeneity and remodeling patterns. This retrospective study included 138 patients with active moderate-to-severe TED (84 responsive; 54 unresponsive), all undergoing water-fat separation imaging before and after IVGC therapy. Four EOM habitat subregions were defined using the Otsu method based on water and fat signal intensity (SI). Volume and volume percentage (VP), including their absolute (Δ) and relative (Δ%) changes post-therapy, were compared between groups. Univariate analysis compared habitat features, while binary logistic regression and receiver operating characteristic (ROC) curve analysis identified valuable parameters for evaluating therapeutic effect. Habitat imaging identified edema (high SIwater and low SIfat) and myosteatosis (low SIwater and high SIfat) subregions. The responsive group exhibited a higher edema VP (32.64 vs 14.13%, P = 0.008) at baseline. After IVGC treatment, the responsive group had a significant decrease in edema VP (32.64 vs 9.85%, P < 0.001); both groups displayed increased myosteatosis, with more pronounced changes observed in the responders. The combination of Δ volume of myosteatosis region and Δ% volume of whole region demonstrated excellent discriminative ability (AUC = 0.86) with high sensitivity (93.75%) in treatment response assessment. Habitat imaging based on water-fat separation provides quantitative visualization of EOM pathological remodeling, establishing myosteatosis as an adjunctive biomarker for evaluating IVGC therapeutic response.

BackgroundA Japanese phase 2 trial of encorafenib plus binimetinib met the primary endpoint of the centrally assessed objective response rate in patients with unresectable BRAF V600E-mutated thyroid cancer. Consequently, encorafenib plus binimetinib has been approved in Japan. We present the health-related quality of life (HR-QoL) outcomes from the trial.MethodsThe multicenter, open-label, uncontrolled phase 2 trial enrolled patients with unresectable locally advanced or metastatic BRAF V600E-mutated thyroid cancer. HR-QoL score, one of the secondary endpoints, was assessed using the EORTC QLQ-C30 and QLQ-THY34 at baseline and during follow-up. The minimal important change (MIC) threshold was set at 10 points.ResultsWe enrolled 22 patients with BRAF V600E-mutated thyroid cancer. The median follow-up was 11.5 months. Completion rates for the questionnaires were 100% (22 of 22 patients) at baseline and 68% (15 of 22) at week 20. Until week 20, changes from baseline were below MIC at most time points in 29 of all 32 domains in QLQ-C30 and QLQ-THY34. In the other 3 domains, patients showed tendencies toward improvement (social support and appetite loss) or deterioration (joint pain) for consecutive time points. Patients with anaplastic thyroid cancer showed tendencies toward improvement for swallowing, restlessness, body image, and discomfort in the head and neck, from the first assessment after the initial treatment.ConclusionThe combination therapy of encorafenib plus binimetinib for unresectable BRAF V600E-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.

ObjectiveGuideline-based lobectomy criteria were adopted in July 2017, and reflexive molecular testing (MT) was introduced for all Bethesda III/IV indeterminate thyroid nodules (ITNs) in July 2020. This study evaluates how reflexive MT of ITNs influenced lobectomy and completion thyroidectomy (CT) rates.MethodsPatients with well-differentiated thyroid cancer who had undergone surgery were identified from a prospective database. Patients were categorized into three groups: i) Bethesda V/VI initial lobectomy, ii) Bethesda III/IV initial lobectomy without MT, iii) Bethesda III/IV lobectomy candidates with MT. The indications for and rates of lobectomy and CT, postoperative complications, and thyroid hormone replacement (THR) were assessed.ResultsFrom July 2017 to October 2023, 227 of 799 (28%) patients with thyroid cancer underwent initial lobectomy, with 91, 70, and 64 patients in each group, respectively. Included in group 3 were 16 ITNs that would have undergone diagnostic lobectomy; however, due to the presence of a malignant mutation, they underwent total thyroidectomy (TT). TT was the appropriate surgery for 15 of 16 patients based on either preoperative lobectomy exclusion criteria or final pathology. CT rates by group were 26, 43, and 27%, respectively (P < 0.05). Vascular invasion, tumor size >4 cm, and aggressive histology were the most common indications for CT. ThyroSPEC was independently associated with a lower likelihood of CT in multivariate analysis. Surgical complications were lower with lobectomy (2%) versus CT (7%), with 44% of lobectomy patients requiring THR.ConclusionReflexive MT for ITNs decreased CT rates by increasing appropriate upfront TT. Lobectomy demonstrated lower rates of surgical complications and THR than two-stage thyroidectomy.

ObjectiveCongenital hypothyroidism is a leading cause of preventable intellectual disability. Neonatal screening enables early detection and treatment, ideally before symptoms appear. In France, screening has been part of national public health policy since 1978, relying on standardized protocols to ensure equity of care. However, the actual adherence to these guidelines and potential local adaptations remain undocumented. This study aimed to describe current practices of French Regional Neonatal Screening Centers and assess their conformity with national recommendations.MethodsIn 2024, a cross-sectional descriptive survey was conducted via a structured online questionnaire sent to all 16 French Regional Neonatal Screening Centers. The questionnaire addressed TSH retesting and referral thresholds, use of thyroxine assays, second-tier testing, resampling protocols, and management of preterm infants. Data were analyzed to identify deviations from guidelines and their potential implications.ResultsAll 16 centers responded (100% response rate). Nine (56%) reported deviations from national recommendations. Five centers applied alternative TSH retesting or referral thresholds. Four measured thyroxine on the first dried blood spot for intermediate TSH levels, with one retrospectively evaluating this approach. Three centers had specific resampling protocols for preterm infants, but none used gestational age-adjusted TSH thresholds. These adaptations aimed to reduce false positives and false negatives associated with the standard protocol.ConclusionThis nationwide survey highlights substantial heterogeneity in congenital hypothyroidism screening practices across France. Variations in TSH thresholds, thyroxine measurement, and preterm infant management may impact diagnostic consistency and equity. Harmonization efforts based on evidence are needed to optimize neonatal screening performance nationally.

IntroductionAmiodarone-induced thyrotoxicosis (AIT) is a serious complication of amiodarone therapy, associated with high morbidity and mortality. Standard medical therapies are often insufficient in refractory cases, and therapeutic plasma exchange (TPE) has been proposed as a bridge to definitive thyroidectomy, although protocols for its use vary and detailed descriptions and definitions of response to therapy are limited.Case presentationWe report four cases of severe refractory AIT, prepared for thyroidectomy with TPE. Patients underwent three to five sessions using either albumin with saline, or combinations including fresh frozen plasma, as replacement fluids. TPE produced variable biochemical effects: free thyroxine (FT4) levels consistently fell during sessions but rarely normalised, while total thyroxine (TT4) normalised in some cases. In most patients, thyroid-stimulating hormone (TSH), previously suppressed for months, rose to detectable levels after only one to two sessions, suggesting a rapid reduction in biologically active thyroid hormone (TH) concentration. TPE was well tolerated overall, although transient coagulopathy and thrombocytopaenia occurred in two cases. All patients proceeded to successful thyroidectomy and achieved post-operative euthyroidism.ConclusionTPE may provide temporary biochemical improvement and clinical stabilisation in refractory AIT, facilitating safe progression to thyroidectomy. However, its biochemical effects can be inconsistent and transient, and complications such as coagulopathy must be anticipated. Our experience supports the use of TPE as a valuable adjunct in selected patients with refractory AIT but illustrates that thyroidectomy should not be unnecessarily delayed in pursuit of complete TH normalisation or rigid biochemical targets.

Long non-coding RNAs (lncRNAs) are untranslated RNA molecules that regulate gene expression through diverse mechanisms, acting as scaffolds, guides, decoys, or signals. In thyroid cancer, the most prevalent endocrine malignancy, lncRNAs are increasingly recognized as key contributors to tumor development and progression. Elucidating these molecular mechanisms is essential for advancing diagnostic, prognostic, and therapeutic strategies. This review highlights major lncRNAs implicated in thyroid cancer, categorizing them as upregulated/oncogenes or downregulated/tumor suppressors and describing their mechanisms of action and interactions. lncRNAs are typically expressed at low levels and tightly regulated to preserve normal cell behavior. In thyroid cancer, they serve as crucial regulators of oncogenesis, frequently acting as competing endogenous RNAs that influence key signaling pathways. While most studies focus on miRNA sponging, other mechanisms are underexplored. Circulating lncRNAs offer potential for non-invasive diagnostics, and several lncRNAs show promise as therapeutic targets. Thus, continued research into the diverse functions of lncRNAs is vital to fully harness their clinical potential in thyroid cancer.

We examined the effect of selenium vs placebo on remission rate and quality of life (QoL) in the Graves' selenium supplementation (GRASS) trial (ID: NCT01611896). Double-blinded, placebo-controlled, multi-centre trial in individuals with newly diagnosed Graves' hyperthyroidism randomised to daily supplementation with 200 μg selenium or placebo tablets during 24-30 months, depending on the timing of antithyroid drug (ATD) withdrawal. The primary outcome was the proportion of participants with non-remission, defined as receiving ATD or remaining hyperthyroid (thyroid stimulating hormone <0.1 mIU/L) during the last 12 months of the intervention period or referral to ablative therapy (radioactive iodine or surgery). QoL was serially assessed by the thyroid-related patient-reported outcome ThyPRO and compared with previously collected norm data. Between Dec 7th 2012 and Dec 3rd 2018, 430 participants with Graves' hyperthyroidism were recruited. Non-remission was observed in 114 (53.3%) participants in the placebo group and 118 (54.6%) in the selenium group (OR = 1.0 (95% CI: 0.7-1.5); P = 0.98). There was no beneficial effect of selenium, as compared with placebo, on any ThyPRO scale. The participants' QoL at the end of the study was comparable to that of the general population sample. Thyrotropin receptor antibody levels were similar in the groups at the 18-month and end-of-study follow-up visits. In individuals with newly diagnosed Graves' hyperthyroidism, daily supplementation with selenium did not have any effects compared with placebo as add-on to standard antithyroid drugs. The GRASS trial findings do not support the use of selenium supplementation in Graves' hyperthyroidism.

ObjectiveDysthyroid optic neuropathy (DON) is a severe complication of thyroid eye disease (TED) with limited early detection methods. This study aimed to investigate the clinical characteristics of patients with TED who developed DON and to establish a predictive model for early identification of high-risk cases.MethodsHerein, 257 TED patients were prospectively included, of whom 68 (26.5%) developed DON. All patients were divided into derivation and validation cohorts, and Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression analyses were applied to identify clinical factors and construct a prediction model.ResultsIn the derivation cohort (185 TED patients), 49 (26.5%) developed DON. DON patients showed significantly higher prevalence of pretibial myxedema (PTM) (22.4 vs 5.9%, P = 0.001), diabetes mellitus (18.4 vs 7.4%, P = 0.029), older age (58.04 ± 11.30 years vs 47.99 ± 10.65 years, P < 0.001), higher CAS (5 vs 4, P < 0.001), elevated triglyceride (TG) levels (1.44 mmol/L vs 1.15 mmol/L, P = 0.042), and lower visual functioning (VF) (43.75 vs 62.50, P < 0.001). LASSO regression analysis identified age, PTM, TG, VF, and CAS as independent predictors of DON. The developed nomogram presented AUCs of 0.853 (95% CI: 0.792–0.914) and 0.856 (95% CI: 0.762–0.950) in the derivation and validation cohorts, respectively.ConclusionsAltogether, the findings of this study identify advanced age, elevated CAS, increased TG, lower VF, and PTM as significant predictors of DON in patients with TED. The proposed nomogram offers a practical clinical tool for risk stratification, providing clinicians with an approach for individualized risk assessment and timely therapeutic intervention.