Thyroid Research最新文献

Background: Thyroid hormones influence the function of essentially every system of the body, including the cardiovascular and metabolic system. Thyroid hormone replacement with levothyroxine (LT4) is the mainstay of pharmacological management for people with (especially clinically overt) hypothyroidism, and it is important to ensure the cardiovascular and metabolic safety of this treatment. This is especially so as in hypothyroidism, cardiometabolic risk factors and cardiovascular disease are highly prevalent conditions and will often coexist in an individual patient. Accordingly, we have reviewed the cardiometabolic consequences of hypothyroidism and intervention with thyroid hormone replacement.

Main body: Numerous observational studies and meta-analyses have described multiple potentially adverse cardiometabolic consequences of hypothyroidism, including exacerbation of cardiovascular and metabolic risk factors (especially dyslipidaemia), functional impairment of the heart and vasculature (including accelerated atherosclerosis) and increased risk of advanced cardiovascular outcomes. LT4 usually improves cardiometabolic risk factors in people with hypothyroidism and some (but not all) studies have reported improved vascular and cardiac function in LT4-treated populations. Observational data have suggested the possibility of improved cardiometabolic outcomes with LT4 treatment, particularly in younger people with hypothyroidism, although data from randomised, controlled trials are needed here. Importantly, LT4 (with or without additional triiodothyronine) appears to be safe from a cardiovascular perspective, as long as overtreatment and iatrogenic thyrotoxicosis are avoided.

Conclusions: Overall, the current evidence base supports intervention with LT4 to protect the cardiometabolic health of people with hypothyroidism who require thyroid hormone replacement, although more data on long-term clinical outcomes are needed.

Introduction: Paediatric Graves' disease (PGD) is an autoimmune condition, which if left untreated, can result in cardiac complications. National Institute for Health and Care Excellence (NICE) Guidance (NG145) advocates the use of antithyroid drugs (ATD) as first-line therapy for PGD, with a consultation to consider a move to definitive therapy in the form of radioactive iodine (RAI) or thyroidectomy if the initial 2-year course failed to achieve normal thyroid function. We aim to evaluate the effectiveness, adverse events, and potential predictors of remission for ATD and RAI in treating PGD.

Methods: A thorough guideline search of NICE Evidence and Royal College of Physicians (RCP) guidelines and policy was conducted to yield a guideline relevant to our review question. A literature search of the Cochrane Library, MEDLINE, EMBASE and PubMed, alongside a clear inclusion and exclusion criteria was utilised to generate systematic reviews and primary literature exploring the efficacy and adverse effects (AEs) of ATD and RAI. Our guideline, systematic reviews and primary literature were appraised using AGREE-II, AMSTAR 2 and CASP respectively.

Results: The search strategy yielded one NICE guideline (NG145) published in November 2019, two systematic reviews published after November 2019 and four primary studies, published after the most recent systematic review (August 2020). All studies concluded that ATD and RAI are effective treatment options for PGD. With regards to AEs, RAI and ATD were safe treatment options, with the latter having the least severity of complications.

Conclusions: In patients who have been identified to have predictors of remission, we agree with NG145 and ATD should be offered as first-line treatment. However, for those who do not have characteristics aligning with the predictors of remission, RAI should be offered as first-line therapy. Future studies should investigate the effect of biochemical parameters to identify predictors of remission, to aid the choice of treatment in paediatric Graves' disease treatment.

Background: Thyroid disorders affect the physical, behavioural, and psychological aspects of an individual, leading to poor self-rated health (SRH). Hence, we aimed to determine the prevalence of poor SRH and the factors associated with it among thyroid disorder patients.

Methods: This is an observational study consisting of 2336 thyroid disorder patients from LASI, 2017-19. Descriptive statistics were employed to calculate prevalence. The association between poor SRH and socio-demographic variables was evaluated using regression analysis, with results expressed as (AOR) and 95% CI.

Results: The findings showed poor self-rated health predictors among thyroid disorder patients, where 25% rated their health as poor. Significant predictors included older age, with patients aged ≥ 75 years having a higher likelihood of reporting poor health (aOR = 2.36, 95% CI = 1.32-4.22, p = 0.004), and rural residence (aOR = 1.34, 95% CI = 1.07-1.67, p = 0.011). Belonging to the OBC caste (aOR = 1.57, 95% CI = 1.23-2.00, p < 0.001) and practicing Christianity (aOR = 1.90, 95% CI = 1.25-2.89, p = 0.003) were also associated with increased odds of poor SRH. Previous employment (aOR = 1.65, 95% CI = 1.20-2.25, p = 0.002), co-morbidities (aOR = 2.59, 95% CI = 1.88-3.59, p < 0.001), and lower education levels (aOR = 1.50, 95% CI = 1.06-2.13, p = 0.022) were significant. Limitations in activities of daily living and instrumental activities of daily living were linked to poorer health outcomes (aOR = 1.76, 95% CI = 1.33-2.31, p < 0.001; IADL: aOR = 1.41, 95% CI = 1.11-1.79, p = 0.004). Depression (aOR = 1.84, 95% CI = 1.32-2.56, p < 0.001) and healthcare utilization in the past year (aOR = 1.86, 95% CI = 1.33-2.58, p < 0.001) also predicted poor SRH, with most healthcare utilization (79.8%) occurring in private facilities.

Conclusion: The study highlights a high prevalence of poor SRH among patients, with significant associations observed with age, residence, comorbidity, and healthcare utilization. Targeted interventions focusing on healthcare access, physical activity, and mental health support are crucial to improve SRH.

Allele Frequency (AF) is the percentage of sequence reads with a specific mutation relative to the read depth at that locus, reflecting the proportion of gene mutation. This review explores the AF characteristics of different mutations in thyroid cancer, investigating their connection with tumor features and clinical characteristics. BRAF mutation AF is associated with tumour malignancy and prognosis, exhibiting a relatively low peak value. TERT mutations in AF are associated with invasive characteristics, and the combination between BRAF and TERT mutations AF improved the diagnostic value in identifying patients' risk of recurrence and tumour malignancy. RET mutation is frequently observed in medullary carcinoma, and RET mutation AF is associated with partial tumour characteristics. RAS mutation is prevalent in follicular tumors, but the association between RAS mutation AF and tumour characteristics is relatively weak. TP53 mutation is more frequently occurred in poorly differentiated and anaplastic carcinoma, and its AF might be associated with the dedifferentiation process. We also concentrated on the mutually exclusive and synergistic effect between different mutations. The mutation rate of TERT increases with the elevation of BRAF mutation AF. Finally, the detection and assessment of AF by NGS in clinical practice helps to provide a reference for individualised targeted therapy plans.

Background: The Tec family of proteins has been identified as a key player in numerous diseases. However, no studies on the associations of Tec family proteins with overall survival (OS) in differentiated thyroid cancer (DTC) patients have been conducted.

Methods: RNA sequencing (RNA-Seq) and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. LASSO-Cox, random forest, and eXtreme Gradient Boosting (XGBoost) analysis methods were used to screen for the genes encoding Tec family proteins that were most closely associated with DTC. A predictive model was developed to estimate the OS of DTC patients. The validity of the prediction model was evaluated via receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and fivefold and 200-fold cross-validation. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the biological functions of the most significant genes.

Results: The AC007494.3 and AC019226.2 genes were most strongly associated with the OS of DTC patients. Therefore, the model can be used to predict the OS of DTC patients. Functional annotation analysis revealed characteristics similar to those of other Tec kinases.

Conclusions: We found that the TEC gene has significant predictive value for the prognosis of DTC patients. The TEC gene has potential value as a target for future drug development. In addition, we recommend more comprehensive treatment and closer monitoring of high-risk populations.

Background: Liquid ethanol-containing levothyroxine (e-LT4) is known to circumvent malabsorption induced by food, drugs, or pathological conditions. Recently a new ethanol-free formulation of liquid levothyroxine (ef-LT4) has been commercialized. No studies have compared e-LT4 with ef-LT4. The aim of the present study is to compare thyroid hormone profile in patients treated with e-LT4 and ef-LT4.

Material and methods: We retrospectively retrieved thyroid hormonal profile and clinical data of 48 patients diagnosed with hypothyroidism who had been on stable treatment with an e- LT4 formulation at the same dosage for at least one year and who decided to switch to ef-LT4 for tasting issue.

Results: A significant increase in TSH levels was observed after 6 months on ef-LT4 treatment (2.5 ± 0.8 mIU/ml vs. 3.1 ± 1.0 mIU/ml, respectively, p < .001), while fT4 decreased [1.2 ng/dl (IQR 1.1-1.4) vs. 1.1 ng/dl (1.0-1.2), respectively, p = .047], maintaining the same dosage of LT4. In 31 patients, for whom data were available 12 months after the switch, TSH further increased (2.50 ± 0.9 mIU/ml at baseline vs 3.2 ± 0.9 mIU/ml after 6 months vs 3.5 ± 0.9 mIU/ml at 12 months, p < .001) and fT4 decreased [1.2 ng/dl (IQR 1.1-1.4) vs. 1.1 ng/dl (IQR 0.9-1.3) vs 1.0 ng/dl (IQR 0.9-1.1), p = .008].

Conclusion: ef-LT4 formulation seems to be less effective compared to e-LT4 over time. However, further prospective cross-sectional studies, performed in large sets of patients, even on concomitant therapy with interfering drugs, are needed.

Background: Value-Based Health Care (VBHC) implementation motivates providers to reduce unnecessary procedures to improve outcomes and costs, i.e.

Value: In thyroid cancer care, adequate use of Fine Needle Aspiration (FNA) may prevent downstream diagnostics, costs, and delays in the care process. This study aims to evaluate the impact of needle selection in FNA on Bethesda I classifications, duration of FNA appointments, and care utilization.

Methods: In October 2021, a Modified Menghini-type needle needle replaced the regular syringe needle used for FNA. An interrupted time series (ITS) analysis using generalized linear models was conducted with data from radiology and pathology reports coupled with care utilization data at the patient level. Outcomes included frequency of Bethesda I classifications per month, appointment time, and health care utilization in the first patient year (in 2024€).

Results: Between July 2020 and May 2022, 345 FNA in 224 patients were included. Implementation of the Modified Menghini-type needle needle was associated with a 78% level decrease in the odds of Bethesda I classification during FNA (OR (95% CI) 0.22 (0.06;0.71)), and, on average, a 4% (1.25 min) reduction in FNA appointment time. Despite a higher FNA unit cost postintervention (additional cost of €17.56 per FNA), there were no changes in the diagnostic and overall costs.

Conclusion: VBHC implementation provides the tools to identify and monitor improvement projects that enhance the value of thyroid nodule diagnostics and management. Implementing a Modified Menghini-type needle needle in FNA resulted in increased adequate diagnostic results, time savings, and no changes in diagnostic and care costs.

Clinical trial number: Not applicable.

Background: Papillary thyroid cancer (PTC) is the most prevalent follicular cell-derived subtype of thyroid cancer. A systems biology approach to PTC can elucidate the mechanism by which molecular components work and interact with one another to decipher a panoramic view of the pathophysiology.

Methodology: PTC associated genes and transcriptomic data were retrieved from DisGeNET and Gene Expression Omnibus database respectively. Published proteomic and metabolomic datasets in PTC from EMBL-EBI were used. Gene Ontology and pathway analyses were performed with SNPs, differentially expressed genes (DEGs), proteins, and metabolites linked to PTC. The effect of a nucleotide substitution on a protein's function was investigated. Additionally, significant transcription factors (TFs) and kinases were identified. An integrated strategy was used to analyse the multi-omics data to determine the key deregulated pathways in PTC carcinogenesis.

Results: Pathways linked to carbohydrate, protein, and lipid metabolism, along with the immune response, signaling, apoptosis, gene expression, epithelial-mesenchymal transition (EMT), and disease onset, were identified as significant for the clinical and functional aspects of PTC. Glyoxylate and dicarboxylate metabolism and citrate cycle were the most common pathways among the PTC omics datasets. Commonality analysis deciphered five TFs and fifty-seven kinases crucial for PTC genesis and progression. Core deregulated pathways, TFs, and kinases modulate critical biological processes like proliferation, angiogenesis, immune infiltration, invasion, autophagy, EMT, and metastasis in PTC.

Conclusion: Identified dysregulated pathways, TFs and kinases are critical in PTC and may help in systems level understanding and device specific experiments, biomarkers, and drug targets for better management of PTC.

Background: Molecular testing is a well-established tool that assists in the management of thyroid nodules and allows classification in distinct molecular alteration patterns: BRAF-like, RAS-like and non-BRAF-non-RAS (NBNR). Yet classical TNM classification and ATA guidelines currently rely on tumor size for risk stratification. In this study, we compared tumor behavior according to molecular alteration patterns versus tumor size.

Methods: Retrospective multicenter multinational study of thyroid nodules that underwent preoperative molecular profiling with ThyGenX/ThyGeNEXT or ThyroSeq V3 between 2015 and 2022. Clinical characteristics, including demographics, cytology results, tumor size, surgical pathology, and molecular alterations, were analyzed.

Results: The study included 718 patients who underwent surgery for papillary thyroid cancer, with a majority of 556 (77.4%) being female. The distribution of molecular alteration patterns was as follows: BRAF-like in 227 (31.6%), RAS-like in 171 (23.8%), NBNR in 59 (8.2%), BRAF/RAS overlap 8 (1.1%) and no detectable mutation in 224 (31.2%) cases. The median tumor size was 15 mm (IQR 10-24). Extrathyroidal extension (ETE) was observed in 6.2% of cases with gross ETE and 5.6% with minimal ETE. Notably, nodules with BRAF-like molecular alterations were more likely to exhibit ETE compared to those with RAS-like or NBNR alterations (P < 0.001). There was no significant correlation between ETE and median tumor size (P > 0.05).

Conclusion: Molecular testing of thyroid nodules provides a more accurate prediction of tumor behavior compared to tumor size alone. These findings suggest that future staging systems could benefit from incorporating molecular alteration patterns into their algorithms.

Background: Evidence regarding the relationship between thyroid hormone levels within the normal range and the incidence of chronic kidney disease (CKD) in adults is scarce. This study aimed to identify the association between thyrotropin (TSH) and free thyroxine (FT4) levels with the incidence of CKD in a large cohort study over long-term follow-up.

Methods: This prospective cohort study, with an 18-year follow-up, included 4118 adults without CKD from the Tehran thyroid Study (TTS). Participants were categorized by tertiles of normal TSH levels (low-normal, middle-normal, and high-normal) and abnormal TSH. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) for CKD incidence based on thyroid hormone levels.

Results: The HR for CKD development was 1.08 (95%CI: 1.01-1.15) per 1 SD increase in the TSH levels. Compared with participants with low-normal TSH levels, those with high-normal (HR:1.37; 95%CI: 1.03-1.84) and abnormal TSH (HR:1.24; 95%CI: 1.05-1.46) had a significantly higher risk of developing CKD. In subgroup analyses, the association between TSH level and CKD was significant in participants younger than 60 years, females, non-obese, non-smokers, and those without diabetes and hypertension. No association was observed between FT4 levels and incident CKD (HR: 0.92; 95%CI: 0.79-1.09). However, a significant association was observed between FT4 levels within the normal range and CKD development in those younger than 60 years old (HR: 0.77; 95% CI: 0.61-0.98).

Conclusion: Increased TSH levels, even within the normal range, linearly increased the risk of CKD even after adjustment for important risk factors. As a result, TSH may potentially be an independent risk factor for incident CKD.