OBJECTIVE:Thyroid nodules diagnosed as atypia of undetermined significance (AUS) are one of the most challenging categories in thyroid cytopathology due to histopathological ambiguity and complexities in clinical management. Therefore, this study aimed to develop and evaluate the diagnostic accuracy of a novel malignancy risk scoring system integrating cytological subclassification and key ultrasonographic features. SUBJECTS AND METHODS:A retrospective analysis was conducted on 357 patients who underwent thyroidectomy following an AUS cytology diagnosis. Cytological samples were subclassified as AUS-N or AUS-O, based on the presence of nuclear atypia, and fundamental sonographic parameters were recorded. Independent predictors of malignancy were identified using multivariable logistic regression, and the AUS-malignancy risk score (AUS-MRS) was developed accordingly. Diagnostic performance was compared with existing classification systems: ACR-TIRADS, EU-TIRADS, and K-TIRADS. RESULTS:The AUS-MRS demonstrated the highest diagnostic performance, with a sensitivity of 84.6%, specificity of 79.6%, and a diagnostic odds ratio (DOR) of 21.8. Among the conventional systems, ACR-TIRADS showed the highest sensitivity (89.1%) but had lower specificity (69.7%) and a DOR of 18.4. EU-TIRADS and K-TIRADS showed more balanced metrics, with sensitivities of 82.7% and 81.4%, specificities of 73.6% and 74.1%, and DORs of 18.2 and 16.7, respectively. The inclusion of nuclear atypia increased specificity across TIRADS models (>85%); however, this was accompanied by reduced sensitivity and did not yield substantial gains in diagnostic performance. CONCLUSION:The AUS-MRS may offer improved diagnostic utility compared to existing ultrasound-based classification systems for assessing malignancy risk in AUS nodules.
OBJECTIVE:We aimed to evaluate temporal changes in the diagnostic performance of thyroid fine-needle aspiration biopsy (FNAB) over a 15-year period in a single-center, surgically confirmed cohort. SUBJECTS AND METHODS:We retrospectively analyzed thyroid FNABs performed between 2009 and 2023, dividing the data into two intervals (Group 1: 2009-2014; Group 2: 2015-2023). All specimens were interpreted by the same two experienced cytopathologists. Sensitivity, specificity, and Youden's J were calculated at four diagnostic thresholds (≥AUS/FLUS, ≥FN/SFN, ≥SM, and malignant only), and level-specific likelihood ratios (LRs) were compared between cohorts. Overall diagnostic discrimination was assessed with receiver operating characteristic (ROC) curves and compared by DeLong's test. RESULTS:The study included 1,241 nodules; after excluding non-diagnostic cytology, 601 nodules in Group 1 and 553 in Group 2 were available for diagnostic performance analysis. At the ≥AUS/FLUS cutoff, sensitivity increased from 85.6% to 94.8%, while specificity declined from 58.4% to 33.0% (both p<0.01). Specificity at higher thresholds remained similar or increased in Group 2. The area under the ROC curve (AUC) was 0.799 for Group 1 and 0.831 for Group 2 (p = 0.24). Of the five Bethesda LRs, only that for AUS/FLUS changed significantly (1.24 vs. 0.37; p<0.01). CONCLUSION:The overall discriminative ability of the Bethesda System remained stable over 15 years. The decrease in the AUS/FLUS LR reflects a spectrum effect driven by more selective surgical referral patterns and should be interpreted as a change in cohort composition rather than diminished test performance.
OBJECTIVE:We investigated the association between physical activity (PA) and arterial stiffness (AS) in Chinese middle-aged and older adults, systematically evaluating the potential mediating role of the Metabolic Score For Visceral Fat. SUBJECTS AND METHODS:Data were drawn from the 2015 China Health and Retirement Longitudinal Study. PA was assessed using the International Physical Activity Questionnaire, and AS was determined by estimated pulse wave velocity. Multivariable logistic regression, restricted cubic spline models, and Bootstrap mediation analysis were applied for statistical analyses. RESULTS:In the fully adjusted model, each standard deviation increase in PA intensity was associated with a 22% reduction in AS risk (odds ratio [OR] = 0.78, 95% confidence interval [CI]: 0.72-0.84, p < 0.001). Compared to low-intensity PA, both moderate-intensity (OR = 0.75, 95% CI: 0.61-0.92, p = 0.005) and high-intensity PA (OR = 0.57, 95% CI: 0.48-0.68, p < 0.001) were significantly associated with a lower risk of AS. Restricted cubic spline analysis revealed a nonlinear association, with AS risk decreasing as PA intensity increased (p-nonlinear = 0.034). Mediation analysis indicated that Metabolic Score For Visceral Fat significantly mediated the negative correlation between PA and AS, accounting for 11.4% of the total effect. CONCLUSION:Among middle-aged and older Chinese adults, higher levels of PA are associated with a lower risk of AS, with this association partially mediated by improvements in visceral fat metabolism.
OBJECTIVE:This study aimed to evaluate the impact of levothyroxine supplementation on neurodevelopmental outcomes in infants with transient hypothyroxinemia of prematurity (THOP). SUBJECTS AND METHODS:In this retrospective observational study, infants born at < 34 weeks of gestation were categorized into three groups: THOP treated with levothyroxine, untreated THOP, and non-hypothyroxinemic controls. Neurodevelopmental outcomes were assessed at 12-72 months of corrected age using the Denver Developmental Screening Test II (DDST-II). RESULTS:Fifty-four infants (40.7% female) with a median gestational age (GA) of 31.0 (28.6-33.0) weeks and mean birth weight of 1414 ± 466 g were included. Infants treated for THOP had significantly lower GA compared with controls (p = 0.037) and lower initial FT4 levels (p < 0.001), while TSH levels were similar (p = 0.581). Prematurity-related morbidities were more frequent in the treated THOP group. No association was observed between DDST-II results and GA, birth weight, or prematurity-related morbidities. The DDST-II results did not differ significantly among treated THOP, untreated THOP, and controls (p = 0.484). CONCLUSION:Levothyroxine supplementation in infants with THOP was not associated with neurodevelopmental outcomes compared with untreated infants with THOP or non-hypothyroxinemic controls. In this cohort, DDST-II results were not significantly associated with GA, birth weight, or major prematurity-related morbidities, suggesting that routine levothyroxine supplementation may not confer a measurable neurodevelopmental benefit. Given the observational design and baseline clinical differences between groups, these findings should be interpreted cautiously. Further multicenter studies with larger cohorts and comprehensive follow-up are needed to clarify whether specific high-risk subgroups may benefit from treatment..
OBJECTIVE:Pediatric Graves' disease (PGD) is a rare autoimmune disorder. Predictors of remission after antithyroid drug (ATD) therapy have been described, but their applicability in pediatric populations remains inconsistent. This study aimed to identify clinical and biochemical factors associated with remission in PGD. SUBJECTS AND METHODS:Retrospective observational study of children diagnosed with Graves' disease at a tertiary hospital in Portugal (2001-2021), all initially treated with ATD. Demographic, clinical, and biochemical data at diagnosis, as well as treatment characteristics, were analyzed. The primary outcome was "In Remission". Secondary outcomes included "Remission Experienced" and "Disease Not Active ≥1 Month". Comparative analyses, logistic regression, and receiver operating characteristic (ROC) curves were applied. RESULTS:Among 45,000 pediatric patients, 36 had PGD (prevalence 0.08%). Median age at diagnosis was 13.7 years; 81% were female, and 78% were pubertal. Methimazole was prescribed in 81%. Mean initial treatment duration (ITD) was 35 months, and 47% of patients underwent definitive therapy. At data collection, 18% of patients were in remission. Longer ITD (>24 months) was associated with remission; the optimal cutoff ITD was 51 months. Smaller thyroid volume and TRAb levels at diagnosis correlated with "Disease Not Active ≥1 Month". Thyroid volume ≥2.5-fold the upper limit of normal (ULN) and TRAb ≥7.055-fold the ULN reduced the likelihood of disease inactivity. CONCLUSION:Prolonged ATD therapy, smaller thyroid volume, and lower TRAb levels at diagnosis were associated with favorable outcomes in PGD. The optimal ITD (≥51 months) supports extended ATD therapy. Larger multicenter studies are warranted to confirm these results.
OBJECTIVE:Transgender individuals often face structural barriers and adverse health outcomes. Provider-to-provider (P2P) consultations may improve the quality of care for this population. This study describes the characteristics, clinical questions, and care provided to transgender population in the Brazilian public primary health care (PHC) system, using data from a P2P telephone consultation service based in Rio Grande do Sul State. SUBJECTS AND METHODS:This cross-sectional study included all consultations classified as related to transgender health care conducted between TelessaúdeRS consultants and PHC professionals from 2015 to 2023. We extracted patient characteristics and clinical questions from each consultation. Continuous data are reported as means ± standard deviations or medians (interquartile ranges), and categorical data as absolute and relative frequencies. RESULTS:Between 2015 and 2023, 752 of the 422,972 total consultations were classified as related to transgender health care. Regarding sex assigned at birth, 47.3% of patients were male, 43.4% were female, and 9.3% were unreported. The mean patient age was 24.5 years (±9.1). The most frequent consultation topics were laboratory monitoring (64.9%), hormone therapy (49.7%), and mental health (28.9%). Nonprescription hormone use was reported by 41.0% of patients. Referrals to specialized care were recommended in 68.4% of cases, and clinical guidance was provided in 71.4%. CONCLUSION:The growing number of P2P consultations reflects an increasing demand for support regarding transgender care within PHC. Frequently asked questions reveal knowledge gaps among PHC providers, and the high rate of unsupervised hormone use suggests persistent barriers to appropriate care. P2P consultations can support PHC professionals in providing safer, more timely transgender health care.
OBJECTIVE:To identify clinicopathologic predictors independently associated with cervical lymph node metastasis in pediatric papillary thyroid carcinoma. SUBJECTS AND METHODS:We performed a retrospective cohort including patients younger than 18 years who underwent total thyroidectomy for papillary thyroid carcinoma (PTC) (2013-2023) at a tertiary pediatric hospital in Brazil. Clinical and histopathologic variables were reviewed per World Health Organisation Classification 5th edition (2022) and the College of American Pathologists protocol (2023). Multivariable associations with cervical lymph node metastasis (LNM) were estimated using Firth's penalized logistic regression; discrimination was summarized by the area under the ROC curve (AUC) with 95% bootstrap confidence intervals. RESULTS:Thirty-two patients were included (median age, 14 years; 81% female). Cervical LNM occurred in 78%. Extrathyroidal extension (ETE) was associated with cervical lymph node metastasis in bivariate analysis (100% vs 59%; p = 0.007) and remained independently associated with cervical lymph node metastasis after adjustment for tumor T stage and lymphatic invasion (OR, 14.29; 95% CI, 1.28-2028.82; p = 0.028). CONCLUSION:ETE was independently associated with cervical lymph node metastasis in pediatric PTC and may justify closer postoperative surveillance.
OBJECTIVE:To quantify the societal burden of obesity in Brazil by estimating years of life lost (YLL) due to premature mortality. SUBJECTS AND METHODS:Given the Brazilian life expectancy of 76.4 years, premature death was defined as occurring before the age of 60. A quantitative epidemiological approach was applied to estimate obesity-attributable YLL in Brazil from 2014 to 2023. Mortality data were obtained from the Mortality Information System, and demographic projections were sourced from the Brazilian Institute of Geography and Statistics. The YLL was calculated by multiplying the number of deaths by the remaining life expectancy (using 2021 Global Burden of Disease reference tables), stratified by age and sex. Statistical analyses were conducted using R software and Python, with results presented as rates per 100,000 population. RESULTS:The total number of events exhibited an upward trend over the decade, with a pronounced peak after 2020, coinciding with the COVID-19 pandemic. The 50-59 and 60-69-year age groups consistently demonstrated the highest event frequencies. Sex-specific analyses revealed variations across age groups and years. Events were rare among those aged 1-14 but increased from age 15-19 onwards. Among older age groups (40-69 years), females exhibited higher rates than males, particularly in the 60-69-age bracket. CONCLUSION:This study demonstrates an increasing trend in obesity-related premature mortality in Brazil, disproportionately affecting older populations and necessitating targeted public health interventions.
OBJECTIVE:This study aimed to evaluate the impact of coexisting autoimmune thyroiditis (HT) on the clinicopathological characteristics and prognosis of patients with papillary thyroid carcinoma (PTC). SUBJECTS AND METHODS:This prospective study included patients diagnosed with papillary thyroid carcinoma who underwent thyroid surgery. Patients were divided into two groups according to the presence or absence of histologically confirmed thyroiditis. Demographic data, tumor characteristics, pathological features, and postoperative outcomes were analyzed. Statistical comparisons were performed to assess differences between the two groups. RESULTS:Thyroiditis was observed in a significant proportion of patients with PTC. Patients with associated thyroiditis showed smaller tumors and more favorable clinicopathological characteristics compared to those without thyroiditis. However, no significant differences were observed in major oncological outcomes. Recurrence rates were lower in the thyroiditis group. The presence of thyroiditis was associated with more favorable prognostic features. CONCLUSION:The coexistence of thyroiditis in patients with PTC was associated with more favorable clinicopathological features. However, no significant differences were observed in major oncological outcomes, and the short follow-up period limits the assessment of long-term prognosis. These findings suggest an association with less aggressive initial presentation rather than a definitive prognostic impact.
OBJECTIVE:To investigate the expression pattern of lncRNA GSEC in papillary thyroid carcinoma (PTC) and elucidate its functional role and molecular mechanism in regulating glycolytic metabolism and malignant progression. MATERIALS AND METHODS:The expression levels of the GSEC gene in thyroid cancer were determined through bioinformatics analysis of the TCGA database, and potential downstream regulatory genes were predicted. GSEC mRNA levels in normal thyroid cells and thyroid cancer cells were detected by qRT-PCR. Cellular functions, including proliferation, invasion, and migration, were evaluated using CCK-8 assays, Annexin-V/PI staining, western blot, EdU staining, Transwell assays, and scratch tests. Glycolytic activity was assessed by western blot, glucose uptake assays, and measurements of extracellular lactate levels. Subcutaneous and metastatic papillary thyroid carcinoma (PTC) models were established in nude mice to investigate the effects of lncRNA GSEC expression on tumor growth and metastasis. RESULTS:LncRNA GSEC expression was significantly downregulated in thyroid cancer. Overexpression of GSEC in PTC-1 cells effectively inhibited their proliferation, invasion, and migration. GSEC downregulated GLUT1 expression by inhibiting IGF2BP2, thereby disrupting glycolysis and suppressing tumor growth and invasion. In vivo assay demonstrated that GSEC overexpression significantly reduced tumor glycolysis, retarded tumor growth, and inhibited metastasis. CONCLUSION:LncRNA GSEC is a key factor in the progression of PTC. By modulating the IGF2BP2/GLUT1 axis, GSEC affects cancer cell glycolysis, presenting a new potential target for metabolic intervention strategies.
OBJECTIVE:This study investigated the association between vitamin D levels and type 2 diabetes mellitus (T2DM) among Indigenous adults of the Tupiniquim and Guarani ethnicities residing on a reserve on the southeastern Brazilian coast. SUBJECTS AND METHODS:This cross-sectional study, conducted between 2020 and 2022, included 946 Indigenous individuals (aged ≥20 years, both sexes) from the Tupiniquim and Guarani ethnic groups. T2DM was defined by a self-reported diabetes diagnosis, the use of glucose-lowering medications, or, in the absence of such reports, a fasting plasma glucose level ≥126 mg/dL, a 2-hour plasma glucose level ≥200 mg/dL following an oral glucose tolerance test, or a glycated hemoglobin level ≥6.5%. Hypovitaminosis D was defined as a serum 25-hydroxyvitamin D [25(OH)D] level <30.0 ng/mL. Associations were estimated using multiple logistic regression models. RESULTS:The mean age of the participants was 41.3 ± 14.9 years; 56.8% were women, and 90% belonged to the Tupiniquim ethnic group. After adjusting for confounders, serum 25(OH)D levels were inversely associated with T2DM. Each 1-ng/mL increase in 25(OH)D was associated with lower odds of T2DM (OR = 0.96; 95% CI: 0.94-0.98). Individuals with hypovitaminosis D had higher odds of T2DM than those with adequate vitamin D levels (OR = 1.77; 95% CI: 1.20-2.62). CONCLUSION:Vitamin D deficiency was independently associated with the presence of T2DM. The high prevalence of hypovitaminosis D underscores the importance of screening strategies and considering supplementation protocols, even among Indigenous populations with high solar exposure.
OBJECTIVE:To evaluate bone density and microstructure, fragility fractures, and hormones in men 50 years and older receiving antiseizure medications (ASMs). SUBJECTS AND METHODS:Study population included 39 men with difficult-to-control epilepsy and 42 healthy men as control group. Spine and hip areal bone mineral density (aBMD), body composition and vertebral fracture assessment (VFA) were evaluated using Dual-Energy X-Ray Absorptiometry (DXA). Volumetric bone mineral density (vBMD) and microarchitecture of trabecular and cortical compartments were evaluated using High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT). Physical activity was tested by the International Physical Activity Questionnaire (IPAQ). The fracture risk was estimated by fracture risk assessment tool (FRAX). RESULTS:ASMs patients showed lower cortical bone thickness (Ct.Th) in distal tibia (1.196 ± 0.295 vs. 1.341 ± 0.241 mm, p = 0.03), more fractures (12 vs. 2, p = 0.003) mostly morphometric vertebral fractures, and a higher risk for major and hip fractures based on FRAX. Hormonal changes included higher median parathyroid hormone (PTH) (50.4 vs. 24 pg/mL, p < 0.001) possibly associated with vitamin D insufficiency, (25(OH)D levels below 30 ng/mL in 43.6% of ASMs patients), lower median Estradiol that was an independent factor for fractures (p = 0.04) and bioavailable Testosterone in the lowest quartile in 52 % of them. CONCLUSION:Men on ASMs exhibit lower Ct.Th and hormone changes that may contribute to bone fragility. While clinical fractures are infrequent, it is crucial to actively search for morphometric fractures, either during DXA or through the more available method of spine X-rays.
OBJECTIVE:To investigate the association between serum vitamin D levels, metabolic syndrome (MetS), and cardiometabolic markers in postmenopausal women from a population-based sample in Brazil. SUBJECTS AND METHODS:This cross-sectional study included 351 women aged 40 to 64 years with at least 12 months of amenorrhea. Serum 25-hydroxyvitamin D was measured by chemiluminescence and categorized into quartiles. MetS was defined according to the Joint Interim Statement criteria. Anthropometric, blood pressure, lipid profile, insulin, calcium, and phosphorus measures were also assessed. RESULTS:Hypovitaminosis D (vitamin D <30 ng/mL) was observed in 66.4% of participants. Women in the highest quartile (≥31.0 ng/mL) had significantly more favorable metabolic profiles than those in the lowest quartile (<21.0 ng/mL), including lower BMI, waist circumference, insulin, and triglycerides, and higher HDL cholesterol. Vitamin D levels <21.0 ng/mL were associated with a 2.27-fold increased risk of MetS (95% CI: 1.21-4.24; p = 0.010). CONCLUSION:Higher vitamin D levels are associated with more favorable metabolic profiles and a reduced risk of MetS in postmenopausal women. Adequate vitamin D status may play a preventive role in mitigating metabolic alterations during postmenopause.
OBJECTIVE:We aimed to evaluate the diagnostic utility of the 30-minute 17-hydroxyprogesterone (17-OHP) measurement during the standard-dose Synacthen test. SUBJECTS AND METHODS:This retrospective study analyzed the medical records of patients aged 0-18 years who underwent Synacthen testing for suspected non-classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency between 2000 and 2024. RESULTS:Among 150 patients included, the median age was 13 years (range 5.5-18), and 85.3% were female. Twenty-nine patients exhibited a peak stimulated 17-OHP level ≥ 10 ng/mL. In three of these patients, the 30-minute 17-OHP level was within normal limits, whereas all had diagnostic 17-OHP levels at 60 minutes. No patients exhibited a diagnostic 17-OHP level at 30 minutes with a non-diagnostic value at 60 minutes. Using a basal 17-OHP cut-off value of 3.78 ng/mL, sensitivity and specificity were 89.7% and 94.2%, respectively. The V281L variant was the most frequently identified pathogenic variant. CONCLUSION:The 60-minute 17-OHP measurement demonstrated greater diagnostic sensitivity than the 30-minute measurement in this cohort and may provide adequate diagnostic information in pediatric patients evaluated for non-classical congenital adrenal hyperplasia, as no additional cases were identified exclusively at the 30-minute time point.
Objective: This study aims to analyze the clinical characteristics and prognostic factors of patients with parathyroid carcinoma (PC) treated at a tertiary institution. Subjects and methods: This retrospective cohort included 30 patients with PC who were treated between 1970 and 2023 at a single reference center. Clinical, pathological, and survival data were reviewed and prognostic factors were evaluated. Results: Of the 30 cases, 16 (53.3%) were women. Mean age at diagnosis was 45.9 years, median follow-up was 60 months and mean tumor size was 33 mm. Median follow-up was 60 months. Disease recurrence occurred in 16 (53.3%) cases, with disease persistence in three (10.0%). Median disease-free survival was 80 months, with a 57% overall survival rate. Neither gender nor age showed significant impact on survival. Patients with lower-stage tumors (T1 by the AJCC/UICC and T1+T2 by the Shaha classification) had significantly better overall survival (p = 0.004 and p = 0.0018, respectively) and disease-free survival (p = 0.03 and p = 0.04, respectively) than those with more advanced stages (p = 0.03 and p = 0.04, respectively). Additionally, patients who experienced tumor recurrence after 36 months had significantly better survival outcomes than those with earlier recurrences (p = 0.02). Conclusion: Advanced tumor stage (T3 by the Shaha or T2 and above by the AJCC/UICC) is associated with higher mortality in patients with PC. Furthermore, a disease-free interval exceeding 36 months emerged as a relevant factor associated with improved overall survival.
