International Journal of Endocrinology最新文献

Objectives: This multicenter cross-country study aimed to assess and compare the short- and long-term efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) in distinct national treatment settings. Materials and Methods: This retrospective study analyzed low-risk PTMC patients who received US-guided RFA at 6 medical centers in 2 countries (Taiwan and Vietnam) between November 2017 and April 2023. US and computed tomography (CT) were performed to assess and compare the PTMC tumors, changes in tumor size, and disease progression. Repeated measure ANOVA and two-way mixed ANOVA were used to analyze within-group and between-group differences among volume and volume reduction ratio (VRR). Student's t-test and the standard chi-square test were used to compare between-group data, while paired t-test was used to compare within-group data. Results: A total of 206 patients (mean age: 44.8 ± 12.5 years [range, 19-87], 44 men) with 224 PTMC tumors were enrolled and treated. Four (1.9%) patients reported transient hoarseness as complications. All tumors exhibited a reduction in size (p < 0.001) at 12 month post-RFA, while 58.5% (131/224) of PTMCs had completely disappeared under US examination at the last follow-up. One patient had developed ipsilateral cervical LN metastasis at the 6-month follow-up. While the VRR showed a statistical difference between the two countries in the short term (p < 0.001), this difference was not observed at 2 year follow-up (p=0.159). Conclusions: US-guided RFA is an effective and safe procedure for patients with PTMC. Furthermore, we noted no long-term differences in terms of procedural outcomes under the distinct national treatment settings.

Background: Osteoporosis represents a critical public health challenge, particularly among postmenopausal women, characterized by reduced bone mineral density (BMD) and increased fracture risk. Traditional obesity metrics such as body mass index (BMI) and waist circumference (WC) have limitations in assessing bone health due to their inability to differentiate lean and fat mass. The weight-adjusted waist index (WWI), a novel anthropometric indicator, offers a more nuanced approach to evaluating body composition and metabolic risks. Objective: The WWI is a novel obesity metric that demonstrates superior accuracy in evaluating both muscle mass and adiposity compared to conventional anthropometric measurements. This cross-sectional study examined the relationship between WWI and BMD at the femoral neck in a nationally representative sample of American postmenopausal women. Methods: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES), including 3198 postmenopausal women aged 40 and older. WWI was calculated by dividing WC by the square root of body weight. BMD was assessed using dual-energy X-ray absorptiometry (DXA). Multivariate regression analyses were performed, adjusting for potential confounders including age, race, height, BMI, and metabolic markers. Results: Multiple regression analyses revealed a significant negative correlation between WWI and femoral neck BMD. A critical threshold of 10.32 was identified, beyond which the relationship with BMD shifted. Below this threshold, higher WWI levels showed a protective effect on BMD (β = 0.03, p=0.0265), while above the threshold, WWI exhibited a significant negative influence (β = -0.01, p < 0.0001). Stratified analyses demonstrated variations in the WWI-BMD relationship across different subgroups, including age, race, and menopause status. Conclusion: This cross-sectional analysis revealed a significant negative correlation between the WWI and femoral neck BMD in a nationally representative cohort of American postmenopausal women. Notably, the association demonstrated a nonlinear inverted U-shaped pattern with an identifiable threshold effect.

Background: Atypical femoral fractures (AFFs) are rare but serious complications of antiresorptive therapy (ART), frequently misdiagnosed and managed inappropriately in acute care settings. Early recognition remains critical to avoid further harm. Objective: To compare the clinical and biochemical characteristics of patients with AFFs and typical femoral fractures (TFFs) to identify features that may assist in diagnosis at the time of hospitalization. Methods: A retrospective study was conducted across two tertiary hospitals in Queensland, Australia, from 2012 to 2022. Patients presenting with femoral shaft fractures were identified using ICD-10 codes. Fractures were classified radiologically using ASBMR criteria. Clinical characteristics, biochemical results, and discharge medications were extracted from electronic records. Between-group comparisons were performed using appropriate statistical tests. Results: Of 869 identified fractures, 43 AFFs and 101 TFFs were confirmed. Patients with AFFs were more likely to have a prior diagnosis of osteoporosis (97.7% vs. 35.6%, p < 0.01), a history of fragility fracture (53.5% vs. 26.7%, p < 0.01), and prodromal symptoms (32.6% vs. 3%, p < 0.01). Biochemically, AFF patients had significantly lower alkaline phosphatase (median 56 vs. 83 IU/L, p < 0.01) and higher 25-hydroxyvitamin D levels (median 86.8 vs. 69.5 nmol/L, p=0.01). Nearly one-quarter had ALP < 40 IU/L. Despite this, 51.3% of AFF patients were discharged on continued ART. Conclusions: Patients with AFFs demonstrate distinct clinical and biochemical profiles at the time of hospital presentation, most notably suppressed ALP. These features may serve as diagnostic clues to prevent ongoing exposure to ART. Greater clinical vigilance is needed to ensure appropriate management and to consider alternative diagnoses such as hypophosphatasia in selected patients.

Aim: This study aimed to analyze the relationship between sensitivity to thyroid hormones and insulin resistance (IR) in people with different levels of body mass index (BMI). Methods: We included 32,478 euthyroid participants, and they were divided into three groups according to body mass index (BMI): normal weight (n = 20,200), overweight (n = 10,178), and obesity (n = 2100). We used the Thyroid Feedback Quantile-based Index (TFQI), the TSH index (TSHI), and the Thyrotroph T4 Resistance Index (TT4RI) to represent thyroid hormones sensitivity and used Triglyceride-Glucose (TyG) Index, the Atherogenic Index of Plasma (AIP), and The Metabolic Score for Insulin Resistance (METS-IR) to represent IR. Results: In the BMI < 25 kg/m² group, linear regression showed that TFQI, TSHI, and TT4RI were all positively correlated with TyG (β = 0.096, 0.089, and 0.089, respectively, all p < 0.001). Logistic regression showed that the odds ratios (ORs) for having high TyG in the highest quartiles of the TFQI, TSHI, and TT4RI were 1.430, 1.537, and 1.518, respectively (all p < 0.001), compared with the lowest quartiles of the TFQI, TSHI, and TT4RI. In the 25 ≤ BMI < 29.9 kg/m² group, TFQI, TSHI, and TT4RI were positively associated with TyG (β = 0.071, 0.067, and 0.066, respectively, all p < 0.001) according to linear regression. The ORs for having high TyG in the highest quartiles of the TFQI, TSHI, and TT4RI were 1.269, 1.363, and 1.353, respectively (all p < 0.001) by logistic regression. In the BMI ≥ 30 kg/m² group, positive correlations were found between the three thyroid indices and TyG (β _TFQI = 0.097, β _TSHI = 0.084, β _TT4RI = 0.083, all p < 0.01) by linear regression. The ORs for having high TyG in the highest quartiles of the TFQI, TSHI, and TT4RI were 1.298 (p=0.101), 1.454 (p=0.05), and 1.455 (p=0.05), respectively. Conclusions: Reduced sensitivity to thyroid hormones was associated with high levels of IR in euthyroid adults of normal weight and overweight. In obese patients, no significant correlation was found between sensitivity to thyroid hormones and IR.

Purpose: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The aim of this study is to identify noninvasive biomarkers for early-stage DKD or targets for DKD treatment through the analysis of urinary exosomal miRNA expression profiles in DKD patients. Methods: The urinary exosomes were isolated from type 2 diabetes (T2DM) patients with DKD confirmed by renal biopsy (DKD-Exo). The urinary exosomal miRNAs expression profiles were detected using miRNA sequencing, and differentially expressed miRNAs were verified by real-time quantitative PCR. Target genes of these miRNAs and relevant pathways in DKD were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Human podocytes and renal tubular epithelial cells (TECs) were treated with DKD-Exo to investigate the effects of DKD-Exo on podocyte apoptosis and the epithelial-mesenchymal transition (EMT) of TECs. Results: A total of 40 miRNAs were found to be differentially downregulated, 17 of which were named and 23 were untitled; miR-371a-3p, miR-371a-5p, miR-1260b, miR-222-3p, miR-1224-5p, and miR-1253 were reported in DKD for the first time. GO and KEGG pathway analyses suggest that these target genes are related to cellular apoptosis and renal fibrosis in DKD, and are involved in 135 pathways. In vitro, DKD-Exo induced the apoptosis of podocytes and collagen synthesis in TECs. Conclusion: Our study implies that the urinary DKD-Exo could deliver biological information to podocytes or TECs, which play an important role in pathogenesis of DKD.

Background/Objective: Thyroid hormones are central to the regulation of energy expenditure and homoeostasis. An important microelement required for the optimal function of the thyroid gland is selenium. The question of whether Nigerian patients with thyroid disorders are deficient in selenium is what this study aims to answer. Methods: This was a comparative cross-sectional study carried out at a tertiary hospital in Southwest Nigeria. Fifty individuals with various thyroid disorders who gave consent were consecutively recruited and compared with one hundred apparently healthy age and sex-matched controls. Blood samples were collected for free thyroxine, free triiodothyronine, thyroid-stimulating hormone and selenium levels. The thyroid hormones were assayed with enzyme-linked immunoassay. Selenium was measured using inductively coupled plasma optical emission spectroscopy. Data were analysed with SPSS Version 26. Results: The mean age of the subjects and control was 40.3 ± 10.6 and 38.0 ± 9.1 years, respectively (p=0.157). The subjects and controls were predominantly females, 80% and 72%, respectively. Thyroid disorders were most prevalent in the 41-50 years age category. The male:female ratio was 1:4. The majority of the cases (60%) had biochemical evidence of hyperthyroidism, 28% were euthyroid and 12% were hypothyroid. Selenium levels were significantly lower among the cases than healthy controls (mean selenium level: 24.9 ± 15.7 and 59.0 ± 35.9 μg/L, respectively, p < 0.001). With normal selenium levels of 80 μg/L, all the participants were deficient in selenium. There was no significant difference in selenium levels across the spectrum of thyroid disorders although the mean selenium levels were lowest for the hypothyroid subjects. Conclusion: There is significant selenium deficiency in all subjects with thyroid disorders; apparently, healthy Nigerians are generally deficient. Selenium supplementation is recommended for Nigerian patients with thyroid disease and may be required for the general population.

Background: The association of vitamin D with metabolic dysfunction-associated fatty liver disease (MAFLD) remained unclear. This study aimed to examine the relationships of total 25-hydroxyvitamin D [25(OH)D, the sum of 25(OH)D₂ and 25(OH)D₃], 25(OH)D₃, and epi-25(OH)D₃ with MAFLD. Methods: We used the National Health and Nutrition Examination Survey of the 2017-2018 cycle for our present analysis. Binary logistic regression analyses were conducted to explore the associations of total 25(OH)D, 25(OH)D₃, and epi-25(OH)D₃ with MAFLD after adjusting for confounders. Interaction tests were conducted to compare the association between 25(OH)D and MAFLD in subgroups. Results: The final analysis included 4605 subjects. After adjustment for confounders, the odds of MAFLD decreased with increasing concentrations of total 25(OH)D (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.29-0.68; p for trend < 0.001). Serum 25(OH)D₃ showed a strong inverse association with MAFLD (OR, 0.39; 95% CI, 0.25-0.59; p for trend < 0.001). In addition, participants with lower epi-25(OH)D₃ levels had a higher likelihood of MAFLD, as demonstrated in both quartile and continuous models (OR, 0.77; 95% CI, 0.60-0.99; p=0.041). After stratification by lipid status, inverse associations of total 25(OH)D and 25(OH)D₃ with MAFLD were found only in dyslipidemic participants (p for interaction < 0.001). A sex-specific interaction was also noted for 25(OH)D₃, showing stronger effects in women than in men (p=0.036). Conclusions: Low serum total 25(OH)D, 25(OH)D₃, and epi-25(OH)D₃ were significantly associated with a higher prevalence of MAFLD. These associations showed nonlinear patterns and were particularly evident among participants with dyslipidemia, with 25(OH)D₃ demonstrating stronger protective effects in women than in men. Given the cross-sectional design, causality cannot be inferred, and further prospective studies are required to confirm these findings.

Purpose: To explore the flavin-containing monooxygenase 3 (FMO3) single-nucleotide polymorphisms (SNPs) and their connection to coronary heart disease (CHD) among Han Chinese with type 2 diabetes (T2D). Methods: The case-control research involved 781 individuals with T2D: 506 CHD cases and 275 controls. The tag-SNPs rs2266780, rs1736557, rs1800822, and rs909530 were selected according to the e!Ensembl database. The genotypes of all the research populations were analyzed via mass spectrometry. SPSS 25.0 software was used to analyze the associations between the selected SNPs and the risk of developing CHD. Results: The rs1800822 T allele frequency was lower in the CHD group than in the non-CHD group (p = 0.049), as was the rs909530 T allele frequency (p = 0.029). The carriers of rs909530 CX genotype had a greater risk of developing CHD than did the TT genotype carriers in the non-premature CHD group (p < 0.001). Conclusion: Our study revealed that rs1800822 and rs909530 in the FMO3 gene may be related to CHD risk among Han Chinese with T2D. We observed a significant gene-by-age interaction at rs909530 on CHD risk, indicating that aging modulates the effect of this locus. Young patients with T2D and the CX genotype may require more stringent management of cardiovascular risk factors.

Background: The selection of thyroid nodules ≤ 10 mm requiring characterization and treatment should be improved, as extensive detection, cytological assessment, and surgery of small and well-differentiated thyroid carcinoma are not cost-effective. Aim: To assess the accuracy of algorithms and ultrasonographic characteristics in selecting actual high-risk thyroid nodules ≤ 10 mm. Methods: A cross-sectional study was conducted on 38 of 112 outpatients who attended the University of Bari and underwent echo-assisted FNA for cytological characterization of thyroid nodules ≤ 10 mm (65 out of 118) and thyroid surgery from January 01 to December 31, 2016. Results: The median age of patients was 49.5 years [16; 69]. Thyroid cytology (SIAPeC-IAP 2014) was classified as TIR1 (one nodule), TIR2 (15), TIR3A (7), TIR3B (10), TIR4 (8), and TIR5 (24). Thirty-nine thyroid nodules were diagnosed as well-differentiated thyroid microcarcinoma. The clinical performance of 4 algorithms widely employed in clinical practice was low (AACE/ACE/AME, 38%; ACR-TIRADS, 45%; K-TIRADS, 60%; EU-TIRADS, 66%). Ultrasonographic features indicating high-risk nodules were hypoechogenicity (p=0.0047), irregular margins (p=0.004), and microcalcifications (p=0.0019). Multivariable analyses indicated that hypoechogenicity was the main ultrasonographic characteristic associated with high-risk nodules (OR = 5.48, p=0.0484). Discussion: Validated algorithms fail to select thyroid nodules ≤ 10 mm for which cytological characterization is needed. Our results are expected to improve the reliability of current algorithms by improving the weight of variables associated with a more consistent risk of thyroid malignancy in nodules ≤ 10 mm.

Purpose: Dietary and exercise interventions have the potential to modify thyroid hormone levels in individuals with obesity. This study investigates the specific mechanisms through which these interventions influence thyroid function, employing a multiomics approach. Methods: 16 volunteers with obesity participated in a two-week regimen of aerobic exercise combined with dietary control. Fasting blood samples and anthropometric measurements were taken before and after the intervention. Serum untargeted lipidomics and metabolomics analyses were performed, alongside evaluations of serum thyroid hormone levels. Additionally, an RNA sequencing dataset was obtained which included gene expression data for skeletal muscle and subcutaneous fat both prior to and following weight loss. Results: Following the intervention, significant alterations were observed in serum levels of thyroid hormones, lipid molecules, and metabolites among participants. Notably, there was a substantial reduction in the levels of tyrosine and phenylalanine (p < 0.001). Furthermore, this intervention had a pronounced effect on the activity of thyroid hormone signaling pathways. Conclusion: Dietary modifications along with exercise facilitate the restoration of thyroid function by enhancing the consumption of tyrosine and phenylalanine while concurrently altering the activity within thyroid hormone signaling pathways. These findings provide valuable insights into potential treatments for obesity-related thyroid dysfunction. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2000040981.