Changing trends in the global, regional, and national burden of iodine deficiency among adolescents and young adults: population-based study.

Iodine is a micronutrient required for the production of thyroid hormones, which regulate metabolism, growth, and neurodevelopment. Iodine deficiency among adolescents and young adults is a major global health issue. We analyzed data from the Global Burden of Disease 2019 database to calculate the prevalence, incidence, and disability-adjusted life-year (DALY) rates of iodine deficiency among adolescents and young adults. We explored the specific year with the most substantial changes in the trends of iodine deficiency among adolescents with annual percentage change (APC) by Joinpoint Regression analysis. Descriptive analyses were conducted to characterize the iodine deficiency burden according to age, sex, location, and sociodemographic index (SDI) quintiles. All measures are listed with 95% uncertainty intervals (UIs), and all rates are reported per 100,000 individuals. From 1990 to 2019, the iodine deficiency prevalence rate among adolescents decreased from 3082.43 (95% uncertainty interval [UI], 2473.01-3855.86) to 2190.84 (95% [UI], 1729.18-2776.16) per 100,000 population, with an AAPC of -1.15 (95% confidence interval [CI], -1.29 to -1.02). Regarding the SDI in 2019, the highest prevalence and DALY rates of iodine deficiency were reported in low-SDI countries. In 1990, Southeast Asia had the highest prevalence and DALYs rates for iodine deficiency among adolescents, while in 2019, Africa had the highest prevalence rate (3330.12). CONCLUSION: Globally, the iodine deficiency burden among adolescents has substantially decreased since 1990; however, low-SDI countries still bear a great burden. Implementation measures and monitoring systems should be strengthened to reduce the iodine deficiency burden, especially among adolescents. WHAT IS KNOWN: • Iodine deficiency can cause severe or irreversible developmental disorders, particularly in adolescents and young adults. • Universal Salt Iodization was implemented for ensuring appropriate iodine intake. WHAT IS NEW: • We found substantial declines in the prevalence rates of iodine deficiency among adolescents during the past three decades. Globally, the disability-adjusted life-year rate of iodine deficiency among adolescents decreased from 56.17 in 1990 to 35.38 in 2019. • Iodine deficiency among adolescents in low- sociodemographic index countries still bear a great burden.

Global, regional, and national burden of type 1 diabetes in adolescents and young adults.

BACKGROUND: Type 1 diabetes (T1D) incidence in adolescents varies widely, but has increased globally in recent years. This study reports T1D burden among adolescents and young adults aged 10-24-year-old age group at global, regional, and national levels. METHODS: Based on the Global Burden of Disease Study 2019, we described the burden of T1D in the 10-24-year-old age group. We further analyzed these trends by age, sex, and the Social Development Index. Joinpoint regression analysis was used to assess temporal trends. RESULTS: T1D incidence among adolescents and young adults increased from 7·78 per 100,000 population (95% UI, 5·27-10·60) in 1990 to 11·07 per 100,000 population (95% UI, 7·42-15·34) in 2019. T1D mortality increased from 5701·19 (95% UI, 4642·70-6444·08) in 1990 to 6,123·04 (95% UI, 5321·82-6887·08) in 2019, representing a 7·40% increase in mortality. The European region had the highest T1D incidence in 2019. Middle-SDI countries exhibited the largest increase in T1D incidence between 1990 and 2019. CONCLUSION: T1D is a growing health concern globally, and T1D burden more heavily affects countries with low SDI. Specific measures and effective collaboration among countries with different SDIs are required to improve diabetes care in adolescents. IMPACT: We assessed trends in T1D incidence and burden among youth in the 10-24-year-old age group by evaluating data from the Global Burden of Disease Study 2019. Our results demonstrated that global T1D incidence in this age group increased over the past 30 years, with the European region having the highest T1D incidence. Specific measures and effective collaboration among countries with different SDIs are required to improve diabetes care in adolescents.

Effects of iodine intake on gut microbiota and gut metabolites in Hashimoto thyroiditis-diseased humans and mice.

Hashimoto thyroiditis (HT) is an organ-specific autoimmune disease linked to iodine intake. Emerging evidence highlights the gut microbiota's role in HT pathogenesis via the microbiota-gut-thyroid axis. However, the process through which iodine intake modifies the microbiota and triggers HT remains unclear. This study examines how iodine affects gut dysbiosis and HT, recruiting 23 patients with HT and 25 healthy individuals to assess gut microbiota composition and metabolic features. Furthermore, we establish a spontaneously developed thyroiditis mouse model using NOD.H-2h4 mice highlighting the influence of iodine intake on HT progression. The butanoate metabolism significantly differs between these two groups according to the enrichment results, and butyric acid is significantly decreased in patients with HT compared with those in healthy individuals. Gut dysbiosis, driven by excessive iodine intake, disrupts TH17/Treg balance by reducing butyric acid. In summary, iodine intake alters intestinal microbiota composition and metabolic changes influencing the microbiota-gut-thyroid axis.

Effects of altitude on thyroid disorders according to Chinese three-rung, ladder-like topography: national cross-sectional study.

BACKGROUND: Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015-2017 that covered all 31 mainland Chinese provinces. METHODS: A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000-500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500-100 m) and B (< 100 m). Associations between geographic factors and thyroid disorders were assessed using linear and binary logistic regression analyses. RESULTS: Participants in the first ladder group were associated with lower thyroid peroxidase (ß = -4.69; P = 0.00), thyroglobulin antibody levels (ß = -11.08; P = 0.01), and the largest thyroid volume (ß = 1.74; P = 0.00), compared with the other groups. The second ladder group was associated with autoimmune thyroiditis (odds ratio = 1.30, 95% confidence interval [1.18-1.43]) and subclinical hypothyroidism (odds ratio = 0.61, 95%confidence interval [0.57-0.66]) (P < 0.05) compared with the first ladder group. Group A (third ladder) (500-100 m) was associated with thyroid nodules and subclinical hypothyroidism (P < 0.05). Furthermore, group B (< 100 m) was positively associated with autoimmune thyroiditis, thyroid peroxidase and thyroglobulin antibody positivity, and negatively associated with overt hypothyroidism, subclinical hypothyroidism, and goiter compared with the first ladder group(P < 0.05). CONCLUSION: We are the first to investigate the association between different ladder regions and thyroid disorders according to unique Chinese topographic features. The prevalence of thyroid disorders varied among the three-rung ladder-like topography groups in China, with the exception of overt hyperthyroidism.

Iodine-induced thyroid dysfunction: a scientometric study and visualization analysis.

Objective: Iodine is essential in thyroid hormone production. Iodine deficiency is associated with serious complications (i.e miscarriage and stillbirth), whereas excess can cause thyroid dysfunction (i.e hyperthyroidism, hypothyroidism, thyroid autoimmunity). We conducted this scientometric study to visualize hot spots and trends in iodine-induced thyroid dysfunction over past two decades. The aim of this paper was to help scholars quickly understand the development and potential trend in this field, and guide future research directions. Methods: Articles on iodine-induced thyroid dysfunction from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) using the following search terms: (((((TS=(hypothyroid*)) OR TS=(hyperthyroid*)) OR TS= ("TSH deficiency")) OR TS= ("thyroid stimulating hormone deficiency")) AND TS=(Iodine)) NOT TS=(radioiodine). Only publications in English were selected. CiteSpace, VOSviewer, Tableau, Carrot2, and R software were used to analyze the contribution and co-occurrence relationships of different countries, institutes, keywords, references, and journals. Results: A total of 2986 publications from 115 countries and 3412 research institutions were included. From 2000 to 2022, research on iodine-induced thyroid dysfunction progressed over a three-stage development period: initial development (2000-2009), stable development (2010-2016), and rapid development (2016-2022) period. The Journal of Clinical Endocrinology and Metabolism had the most co-citations followed and China Medical University (n=76) had the most publications. The top three clusters of co-citation references were isolated maternal hypothyroxinemia, subclinical hyperthyroidism, and brain development. Various scientific methods were applied to reveal acknowledge structure, development trend and research hotspots in iodine-induced thyroid dysfunction. Conclusion: Our scientometric analysis shows that investigations related to pregnant women, epidemiology surveys, and iodine deficiency are promising topics for future iodine-induced thyroid dysfunction research and highlights the important role of iodine on thyroid function.

A Systematic Review and Meta-Analysis Examining the Risk of Adverse Pregnancy and Neonatal Outcomes in Women with Isolated Hypothyroxinemia in Pregnancy.

Background: The relationship between isolated hypothyroxinemia (IH) in pregnancy and adverse pregnancy outcomes is controversial, with no consensus on the need for treatment. Summary: We conducted a systematic review and meta-analysis examining adverse pregnancy and neonatal outcomes in women with IH in pregnancy. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for publications from inception to December 2022. Randomized clinical trials and cohort studies were included. Random-effects meta-analyses were used to estimate pooled relative risks (RRs) for each outcome. We included 21 articles, of which 19 investigated the relationship between IH and maternal and neonatal outcomes and 4 investigated the efficacy of levothyroxine (LT4) treatment. Compared with euthyroid pregnancies, IH pregnancies were associated with an increased risk of preterm birth (RR 1.35 [confidence interval, CI, 1.16-1.56]; I2 = 9%), premature rupture of membranes (RR 1.41 [CI 1.08-1.84]; I2 = 0%), gestational diabetes (RR 1.34 [CI 1.07-1.67]; I2 = 76%), macrosomia (RR 1.62 [CI 1.31-2.02]; I2 = 42%), and fetal distress (RR 1.72 [CI 1.15-2.56]; I2 = 0%). However, no statistically significant differences were noted in adverse outcomes according to LT4 treatment status. Conclusions: There is evidence suggesting that IH in pregnancy may be associated with an increased risk of adverse pregnancy and neonatal outcomes. However, it is unclear whether LT4 may mitigate the risk of these adverse outcomes.

A novel signature to predict thyroid cancer prognosis and immune landscape using immune-related LncRNA pairs.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy worldwide. The incidence of TC is high and increasing worldwide due to continuous improvements in diagnostic technology. Therefore, identifying accurate prognostic predictions to stratify TC patients is important. METHODS: Raw data were downloaded from the TCGA database, and pairwise comparisons were applied to identify differentially expressed immune-related lncRNA (DEirlncRNA) pairs. Then, we used univariate Cox regression analysis and a modified Lasso algorithm on these pairs to construct a risk assessment model for TC. We further used qRT‒PCR analysis to validate the expression levels of irlncRNAs in the model. Next, TC patients were assigned to high- and low-risk groups based on the optimal cutoff score of the model for the 1-year ROC curve. We evaluated the signature in terms of prognostic independence, predictive value, immune cell infiltration, immune status, ICI-related molecules, and small-molecule inhibitor efficacy. RESULTS: We identified 14 DEirlncRNA pairs as the novel predictive signature. In addition, the qRT‒PCR results were consistent with the bioinformatics results obtained from the TCGA dataset. The high-risk group had a significantly poorer prognosis than the low-risk group. Cox regression analysis revealed that this immune-related signature could predict prognosis independently and reliably for TC. With the CIBERSORT algorithm, we found an association between the signature and immune cell infiltration. Additionally, immune status was significantly higher in low-risk groups. Several immune checkpoint inhibitor (ICI)-related molecules, such as PD-1 and PD-L1, showed a negative correlation with the high-risk group. We further discovered that our new signature was correlated with the clinical response to small-molecule inhibitors, such as sunitinib. CONCLUSIONS: We have constructed a prognostic immune-related lncRNA signature that can predict TC patient survival without considering the technical bias of different platforms, and this signature also sheds light on TC's overall prognosis and novel clinical treatments, such as ICB therapy and small molecular inhibitors.

Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis.

Background: Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID. Methods: We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD. Results: The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto's thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves' disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls. Conclusions: This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels. Systematic Review Registration: PROSPERO, identifier CRD42021251557.

Nanotherapy Targeting the Tumor Microenvironment.

Cancer is characterized by high mortality and low curability. Recent studies have shown that the mechanism of tumor resistance involves not only endogenous changes to tumor cells, but also to the tumor microenvironment (TME), which provides the necessary conditions for the growth, invasion, and metastasis of cancer cells, akin to Stephen Paget's hypothesis of "seed and soil." Hence, the TME is a significant target for cancer therapy via nanoparticles, which can carry different kinds of drugs targeting different types or stages of tumors. The key step of nanotherapy is the achievement of accurate active or passive targeting to trigger drugs precisely at tumor cells, with less toxicity and fewer side effects. With deepened understanding of the tumor microenvironment and rapid development of the nanomaterial industry, the mechanisms of nanotherapy could be individualized according to the specific TME characteristics, including low pH, cancer-associated fibroblasts (CAFs), and increased expression of metalloproteinase. However, some abnormal features of the TME limit drugs from reaching all tumor cells in lethal concentrations, and the characteristics of tumors vary in numerous ways, resulting in great challenges for the clinical application of nanotherapy. In this review, we discuss the essential role of the tumor microenvironment in the genesis and development of tumors, as well as the measures required to improve the therapeutic effects of tumor microenvironment-targeting nanoparticles and ways to reduce damage to normal tissue.

Cpt1c regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions.

Background: Cancer cells have to take metabolic transformation in tumor progression when facing need of increased energy and adequate vascularization. However, molecular mechanism is not fully known. In this study, we showed that expression of carnitine palmitoyltransferase 1C (Cpt1c), as a member of the gate-keeper enzymes , which transferring long-chain fatty acids into mitochondria to further oxidation, which is regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions. Methods: Firstly, we used qRT-PCR to detect expression of Cpt1c in papillary thyroid carcinomas tissues compared with paired normal tissues. Secondly, to evaluate whether Cpt1c is induced under metabolic stress, models of hypoxia (0.2% oxygen) and glucose deprivation for cultured papillary thyroid carcinomas cells were established. Lastly, KTC-1 cells were treated with AICAR (as an agonist of AMPK) and Compound C (as an inhibitor of AMPK) to investigate the correlation of AMPK activity with Cpt1c expression under metabolic stress. Results: Cpt1c is higher in papillary thyroid carcinomas tissues compared with paired normal tissues. Furthermore, Cpt1c up-regulation promotes cancer cell growth and metastasis. In addition, the results showed that Cpt1c expression is induced by metabolic stress, including hypoxia and low glucose treatment. Consistently, Cpt1c can protect cells from cancer cells death caused by hypoxia and low glucose. Lastly, Cpt1c expression is regulated by AMPK activity. Conclusion: Here we describe that induction of Cpt1c expression facing metabolic stress in papillary thyroid carcinomas is at least partly regulated by AMPK activity and ultimately contribute to development and progression of papillary thyroid carcinomas.