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ABSTRACT Objective: To set cutoff points for the triglyceride and glucose index (TyG) as a marker of insulin resistance (IR) for the pediatric population. Subjects and methods: This was a cross-sectional study with schoolchildren population-based data using data of 377 schoolchildren age 10 to 17 years of both sexes. We studied metabolic variables associated with IR indicators, such as fasting insulin and blood glucose, to calculate the homeostatic model assessment (HOMA-IR), and we studied triglycerides (TG) to determine the TyG index. We obtained TyG cutoff values for IR using the receiver operation characteristic (ROC), with definitions of sensitivity (Sen), specificity (Spe), and area under the ROC curve (AUC), with the HOMA-IR as reference. Results: The cutoff points of the TyG index for IR in adolescents are 7.94 for both sexes, 7.91 for boys, and 7.94 for girls, indicating moderate discriminatory power. When we also considered anthropometric variables of excess weight [TyG-BMI (body mass index)] and visceral fat [TyG-WC (waist circumference)], these indexes reached AUC values higher than 0.72, enhancing their potential use for a good diagnosis. Conclusion: TyG has proven to be a useful instrument for identifying IR in adolescent health screening, with high discrimination capacity when added to anthropometric variables, making it a feasible and inexpensive option.

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ABSTRACT Objective: To analyze different anatomical sites in the abdominal region, in order to determine the positional parameter that identifies a higher level of visceral adipose tissue (VAT) and confers a greater cardiometabolic risk. Materials and methods: This is a methodological study in which VAT was evaluated by ultrasonography (USG) in three anatomical sites in the abdomen, while the abdominal circumference (AC) was measured using seven different protocols. Additionally, the glycemic and lipid profile, C-reactive protein, and the presence of systemic arterial hypertension were evaluated. Results: One hundred and six individuals with an average age of 42 (36.8-46.2) years were included. The evaluation of the calibration of the ultrasound procedure for the analysis of VAT by intra- and inter-evaluators showed high reproducibility. The pattern of abdominal fat distribution differed between sexes, with higher mean VAT in males (p < 0.05) and higher mean SAT (subcutaneous adipose tissue) in females (p < 0.005). In the abdominal scan applied to women, higher levels of VAT and lower levels of SAT were observed in the narrower waist region, between the iliac crest and the last rib (p < 0.001). In males, the profile of adipose disposition along the abdomen was uniform (p > 0.05). Correlations between VAT measured by USG and cardiometabolic parameters were relatively stronger in the upper abdomen (p < 0.05). Conclusion: Women accumulate more VAT in the narrower waist region, while men accumulate VAT uniformly across the abdomen. There was relative superiority in predicting cardiometabolic risk in the upper abdomen for both sexes.

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ABSTRACT Objectives: Papillary thyroid carcinoma (PTC) accounts for approximately 85%-90% of all thyroid cancers. Of the iodine-metabolizing genes, BRAFV600E is a highly specific target for PTC and may have a reciprocal causative relationship with iodide-metabolizing genes. Materials and methods: In this study, we performed a data analysis of selected quantitative studies to determine the relationship between iodine nutritional status and the prevalence of the BRAF600E mutation in patients with PTC. Five studies were selected for meta-analysis based on the selection criteria. Results: A total of 2,068 patients were divided into three groups: low (urinary iodine concentration [UIC] < 100 μg/L), adequate (UIC 100-200 μg/L), and high (UIC ≥ 200 μg/L). The results were obtained using RevMan software, and the pooled odds ratios (ORs) were calculated using Mantel-Haenszel statistics with a 95% confidence interval (CI). The OR for the prevalence of the BRAFV600E mutation between the high and adequate groups was 1.25 (95% CI 0.64-2.43, p = 0.51), and the OR between the low and adequate groups was 0.98 (95% CI 0.42-2.31, p = 0.96). The BRAFV600E mutation risk did not change significantly at different levels of iodine nutrition (p = 0.33) in statistical analyses. Conclusion: We conducted preliminary research on dietary iodine intake and the BRAFV600E mutation in PTC. The results suggested that abnormal iodine intake might not directly influence the prevalence of the BRAFV600E mutation in these patients. Further research into the associations between dietary iodine intake and the BRAFV600E mutation in PTC, including the underlying mechanisms, is required.

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ABSTRACT Objective: This study aimed to investigate the frequency of sexual dysfunction and the effect of short-term testosterone replacement therapy on sexual functions in congenital hypogonadism patients. Furthermore, we sought to reveal the consistency of the self-report scales used for the diagnosis of sexual dysfunction and the relationship between biochemical parameters. Materials and methods: The study was conducted on 47 young male patients aged above 18 years who were diagnosed with hypogonadotropic hypogonadism. Short (IIEF-5) and long (IIEF-15) forms of the International Index of Erectile Function and Arizona Sexual Experiences Scale (ASEX) were applied before treatment under the supervision of a physician. The patients’ blood pressure, height, and weight were measured, and their luteinizing hormone (LH), FSH, and total testosterone levels were recorded. Patients who started their treatments were called for a follow-up checkup after 6 months. Their blood pressure, height, and weight were measured by reapplying the ASEX, IIEF-5, and IIEF-15. In addition, their LH, FSH, and total testosterone levels in the biochemical tests were rerecorded. Results: In this study, the sexual dysfunction status of patients diagnosed with hypogonadotropic hypogonadism before and after treatment was evaluated using the ASEX, IIEF-15, and IIEF-5 scales. A decrease in sexual dysfunction was observed in all three scales after treatment compared with that before treatment. The IIEF-5 and IIEF-15 scales were found to be uncorrelated in terms of the pretreatment values but were correlated in terms of the post-treatment values. Although a correlation was observed between ASEX and IIEF-5 before treatment, no correlation was detected between ASEX and IIEF-15. After the treatment, ASEX was found to be correlated with both IIEF-5 and IIEF-15. The results of the scales indicated the correlation in all categories, except the pretreatment results of the IIEF-15 scale. Conclusion: The results of the current study demonstrated a significant improvement in the sexual function of hypogonadism patients undergoing short-term testosterone therapy. The ASEX, IIEF-5, and IIEF-15 scales used in the diagnosis and follow-up of sexual dysfunction were useful for evaluating sexual functions in hypogonadotropic hypogonadism patients.

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ABSTRACT Objectives: Congenital hypothyroidism (CH) can be permanent (PCH) or transient (TCH). While the importance of thyroxine in myelination of the brain is undisputed, the benefits to neurodevelopmental outcomes of TCH treatment are controversial. Our objectives were to determine predictive factors for PCH and verify its prevalence changes over time. Subjects and methods: A total of 165 children were evaluated at 3 years of age to verify the diagnosis of PCH. 130 were submitted to a two-step cluster analysis, with the aim of grouping them into homogeneous clusters. The mean incidence of PCH and TCH was calculated from 2004 to 2010 and 2011 to 2015. Results: Sixty-six children were diagnosed with PCH, and 99 were diagnosed with TCH. Eighty-one percent of PCH children and all TCH children with thyroid imaging had glands in situ. Eighty children (61.5%) were in Cluster 1, 8 children (6.2%) were in Cluster 2 and 42 children (32.3%) were in Cluster 3. No children had PCH in Cluster 1, while 87.5% of children in Cluster 2 and all children in Cluster 3 had PCH. The most important predictor for PCH was the initial serum TSH, which was marginally higher in importance than the blood spot TSH, followed by the initial serum free T4. The mean incidence of PCH (odds ratio: 1.95, 95% CI 1.36 to 2.95, p < 0.0001) and TCH (odds ratio 1.33, 95%, CI 1.02 to 1.77, p = 0,038) increased over time. Conclusions: The most important PCH predictors are the initial serum TSH and the blood spot TSH. The mean incidence of both PCH and TCH in our series increased.

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ABSTRACT Objective: The purpose of this study was to investigate the effect and influencing factors of post-surgical radioactive iodine (RAI) therapy for patients with low- and intermediate-risk differentiated thyroid cancer (DTC). Subjects and methods: A retrospective analysis of 423 low- and intermediate-risk DTC patients admitted to the Department of Nuclear Medicine, Sichuan Provincial People’s Hospital from January 2005 to December 2020 was performed. All patients were treated with surgery, had a postoperative pathological diagnosis, and were treated with RAI, including 89 males and 334 females. Recurrence risk stratification: 143 cases were low-risk, and 280 cases were intermediate-risk. Results: The excellent response (ER) rate for low- and intermediate-risk were 93.7% and 78.2%, respectively (P < 0.05). There were significant differences in age, cumulative dose of [131I], and pretreatment stimulated-Tg (pre-Tg) levels between the low- and intermediate-risk groups (P < 0.05). There were significant differences in the cumulative dose of 131I and pre-Tg levels between ER and the non-ER group (P < 0.05). The area under the curve (AUC) values were 0.799 in the low-risk group, and 0.747 in the intermediate-risk group for the ROC curve by ER status of pre-Tg. The ER rate with RAI treatment decreased with an increase in pre-Tg levels. Conclusion: Pre-Tg was an important factor for RAI treatment decision-making and prognostic evaluation and differed between low-risk and intermediate-risk DTC. Aggressive RAI therapy was recommended for low-risk DTC with pre-Tg ≥ 20.0 ng/mL and in intermediate-risk group with pre-Tg ≥ 10.0 ng/mL.

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Abstract Objective: The aim of the study is to compare the quality of life, physical activity, anxiety, depression, fear of hypoglycemia, loneliness perception in patients with type 1 diabetes mellitus and controls. Subjects and methods: Forty-four patients and 63 controls were included in this cross-sectional study. Quality of life (Short Form 36-SF-36), physical activity level (International Physical Activity Questionnaire-short form), anxiety and depression (Hospital Anxiety and Depression Scale), fear of hypoglycemia (Hypoglycemia Fear Survey), loneliness perception (UCLA Loneliness Scale) were evaluated. Results: Physical role limitations and general health perception subscale scores of SF-36 questionnaire in patients were significantly lower than the controls (p < 0.05). Conclusion: Role limitations due to physical problems and fear of hypoglycemia are increased, and general health perception is impaired in patients with type 1 diabetes mellitus. Physical inactivity is an important symptom in individuals in the pandemic period. In this regard, telerehabilitation approaches will be beneficial for all individuals in increasing physical activity, improving quality of life, and decreasing anxiety, depression and loneliness perception during the pandemic period for all individuals. The importance of a multidisciplinary approach in diabetes management and dealing with problems should be considered in pandemic.

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ABSTRACT Objective: To evaluate the expression of UCP1, UCP2, and UCP3 mRNA and encoded proteins in epicardial and mediastinal adipose tissues in patients with coronary artery disease (CAD). Subjects and methods: We studied 60 patients with CAD and 106 patients undergoing valve replacement surgery (controls). Expression levels of UCP1, UCP2, and UCP3 mRNA and encoded proteins were measured by quantitative real-time PCR and Western blot analysis, respectively. Results: We found increased UCP1, UCP2, and UCP3 mRNA levels in the epicardial adipose tissue in the CAD versus the control group, and higher UCP1 and UCP3 mRNA expression in the epicardial compared with the mediastinal tissue in the CAD group. There was also increased expression of UCP1 protein in the epicardial tissue and UCP2 protein in the mediastinum tissue in patients with CAD. Finally, UCP1 expression was associated with levels of fasting plasma glucose, and UCP3 expression was associated with levels of high-density lipoprotein cholesterol and low-density cholesterol in the epicardial tissue. Conclusions: Our study supports the hypothesis that higher mRNA expression by UCP genes in the epicardial adipose tissue could be a protective mechanism against the production of reactive oxygen species and may guard the myocardium against damage. Thus, UCP levels are essential to maintain the adaptive phase of cardiac injury in the presence of metabolic disorders.

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Abstract Objective: Arterial hypertension (AH) is a risk factor for cardiovascular diseases (CVD). We sought to evaluate the association between two adiposity indices (visceral adiposity index [VAI] and lipid accumulation product [LAP]) with traditional markers of cardiometabolic risk in hypertensive patients. Materials and methods: This is a cross-sectional study with 1,273 subjects with hypertension treated as outpatients at a university hospital. The VAI and LAP were calculated using formulas stratified by sex. Cardiometabolic risk variables were considered: overweight, risk for waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHA), and altered biochemical test values. The predictive effect of independent variables on outcomes was assessed by multivariate linear regression analysis. There was statistical significance when p ≤ 0.05. Results: Higher cardiometabolic risk (according to BMI, WHR, WHA, and altered biochemical parameters) was associated with higher values of VAI and LAP with statistical significance (p ≤ 0.05). The regression models used explained 30.7% and 10.5% of the changes in LAP and VAI, respectively. Conclusion: LAP and VAI are associated with cardiometabolic risk parameters in the individuals evaluated, suggesting that these indices can be used to screen for CVD risk in individuals with AH.

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Abstract Objective: Resting energy expenditure (REE) decreases if there is reduced energy intake and body weight (BW). The decrease in REE could make it difficult for patients with obesity to maintain decreased BW. This study aimed to investigate the correlation among changes in REE, energy intake, and BW during the weight loss process in patients with obesity. Materials and methods: We conducted a retrospective cohort study of patients hospitalized for the treatment of obesity in Japan. Patients received fully controlled diet during hospitalization and performed exercises if able. REE was measured once a week using a hand-held indirect calorimetry. Energy intake was determined by actual dietary intake. Results: Of 44 inpatients with obesity, 17 were included in the analysis. Their BW decreased significantly after 1 week (−4.7 ± 2.0 kg, P < 0.001) and 2 weeks (−5.7 ± 2.2 kg, P < 0.001). The change in REE after 1 and 2 weeks was positively correlated with the energy intake/energy expenditure ratio (r = 0.66, P = 0.004 at 1 week, r = 0.71, P = 0.002 at 2 weeks). Using a regression equation (y = 0.5257x – 43.579), if the energy intake/energy expenditure ratio within the second week was 82.9%, the REE after 2 weeks was similar to the baseline level. There was no significant correlation between the change in REE and BW. Conclusions: Our data suggest that changes in REE depend on energy intake/energy expenditure ratio and that the decrease in REE can be minimized by matching energy intake to energy expenditure, even during the weight loss process.

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ABSTRACT Objective: This study aimed to investigate the association between 25OHD (total, bioavailable and free) with bone mass and microarchitecture among primary hyperparathyroidism (PHPT) patients and controls. Subjects and methods: Sixty-four patients in the preoperative period of PHPT and 63 matched controls, who had not taken vitamin D in the last three months. To calculate the bioavailable and free 25OHD, the genetic variants of the vitamin D-binding protein (DBP) were determined. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry (DXA). The distributions of total, bioavailable and free 25OHD and their correlation with TBS and DXA were evaluated. Results: PHPT showed BMD and TBS values lower than CTRL in all locations (p < 0.05). There were no statistical differences in the levels of free, bioavailable and total 25OHD between the PHPT and CTRL groups [mean, min-max: 3.4 (1.4-8.6) vs. 3.1 (1.0-9.8) pg/mL, 1.51 (0.43-3.58) vs. 1.41 (0.38-3.48) ng/mL, 22.6 (11.0-39.9) vs. 20.6 (8.9-35.3) ng/dL, respectively; (p > 0.05). The distribution of DBP haplotypes was similar between groups. DXA showed no correlation with any form of 25OHD in both groups. TBS presented a weak correlation with the total 25OHD in PHPT (r = 0.28; p = 0.02) and a moderate correlation with the total, free and bioavailable 25OHD in CTRL (r = 0.42; r = 0.42; r = 0.43; respectively, p < 0.01). Conclusion: The concentrations of total, free and bioavailable 25OHD were similar in both the PHPT and control groups. 25OHD concentrations correlated positively with TBS and not with DXA, especially in controls, suggesting that this method may be more sensitive to assessing the consequences of vitamin D deficiency on bone quality in individuals without PHPT.

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ABSTRACT Objective: We investigated the prevalence of adrenal incidentalomas (AIs) in a nonselected Brazilian population in chest computed tomography (CT) performed during the COVID-19 pandemic. Materials and methods: This was a retrospective cross-sectional observational study using chest CT reports from a tertiary in- and outpatient radiology clinic from March to September 2020. AIs were defined by changes in the shape, size, or density of the gland initially identified in the released report. Individuals with multiple studies were included, and duplicates were removed. Exams with positive findings were reviewed by a single radiologist. Results: A total of 10,329 chest CTs were reviewed, and after duplicate removal, 8,207 exams were included. The median age was 45 years [IQR 35-59 years], and 4,667 (56.8%) were female. Thirty-eight lesions were identified in 36 patients (prevalence 0.44%). A higher prevalence was observed with age, with 94.4% of the findings in patients aged 40 years and over (RR 9.98 IC 2.39-41.58, p 0.002), but there was no significant difference between the sexes. Seventeen lesions (44.7%) had more than 10 HU, and five lesions (12.1%) were more than 4 cm. Conclusions: The prevalence of AIs in an unselected and unreviewed population in a Brazilian clinic is low. The impact on the health system caused by AIs discovered during the pandemic should be small regarding the need for specialized follow-up.

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ABSTRACT Objective: The aim of this study was to investigate how polarized sodium iodide symporter (NIS) expression may regulate iodide metabolism in vivo. Materials and methods: Polarized NIS expression was analyzed in tissues that accumulate iodide by the use of immunohistochemistry and polyclonal antibody against the C-terminal end of human NIS (hNIS). Results: Iodide absorption in the human intestine occurs via NIS expressed in the apical membrane. Iodide is secreted into the lumen of the stomach and salivary glands via NIS expressed in the basolateral membrane and then circulates back from the small intestine to the bloodstream via NIS expressed in the apical membrane. Conclusion: Polarized NIS expression in the human body regulates intestinal-bloodstream recirculation of iodide, perhaps prolonging the availability of iodide in the bloodstream. This leads to more efficient iodide trapping by the thyroid gland. Understanding the regulation and manipulating gastrointestinal iodide recirculation could increase radioiodine availability during theranostic NIS applications.

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ABSTRACT Objective: To define the mathematical relationship between fructosamine levels and average glucose values. Subjects and methods: The study comprised laboratory data of 1,227 patients with type 1 or 2 diabetes mellitus. Fructosamine levels measured at the end of a 3-week period were compared against the average blood glucose levels of the previous 3 weeks. Average glucose levels were determined by the weighted average of the daily fasting capillary glucose results performed during the study period, and the plasma glucose measured in the same sample collected for fructosamine measurement. Results: In total, 9,450 glucose measurements were performed. Linear regression analysis between fructosamine levels and average glucose levels showed that for each 1.0 µmol/L increase in fructosamine level there was a 0.5 mg/dL increase in average glucose level, as estimated by the equation Mean glucose level = (0.5157 x Fructosamine) – 20. The coefficient of determination (r2 = 0.353492, p < 0.006881) allowed the calculation of the estimated average glucose based on fructosamine level. Conclusion: Our study demonstrated a linear correlation between fructosamine level and mean blood glucose level, suggesting that fructosamine levels can be a proxy for the average glucose level in assessing the metabolic control of patients with diabetes.

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ABSTRACT Research from the last 20 years has provided important insights into the molecular pathogenesis of craniopharyngiomas (CPs). Besides the well-known clinical and histological differences between the subtypes of CPs, adamantinomatous (ACP) and papillary (PCP) craniopharyngiomas, other molecular differences have been identified, further elucidating pathways related to the origin and development of such tumors. The present minireview assesses current knowledge on embryogenesis and the genetic, epigenetic, transcriptomic, and signaling pathways involved in the ACP and PCP subtypes, revealing the similarities and differences in their profiles. ACP and PCP subtypes can be identified by the presence of mutations in CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively. Therefore, β-catenin accumulates in the nucleus-cytoplasm of cell clusters in ACPs and, in PCPs, cell immunostaining with specific antibody against the V600E-mutated protein can be seen. Distinct patterns of DNA methylation further differentiate ACPs and PCPs. In addition, research on genetic and epigenetic changes and tumor microenvironment specificities have further clarified the development and progression of the disease. No relevant transcriptional differences in ACPs have emerged between children and adults. In conclusion, ACPs and PCPs present diverse genetic signatures and each subtype is associated with specific signaling pathways. A better understanding of the pathways related to the growth of such tumors is paramount for the development of novel targeted therapeutic agents.

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ABSTRACT To conduct a systematic review and meta-analysis of studies assessing the association between serum vitamin D status and mortality in patients with COVID- 19. We searched PubMed and Embase for studies addressing the association of serum vitamin D levels and COVID-19 mortality published until April 24, 2022. Risk ratios (RRs) and 95% confidence interval (CIs) were pooled using fixed or random effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. The meta-analysis included 21 studies that measured serum vitamin D levels close to the date of admission, of which 2 were case- control and 19 were cohort studies. Vitamin D deficiency was associated with COVID-19 mortality in the overall analysis but not when the analysis was adjusted to vitamin D cutoff levels < 10 or < 12 ng/mL (RR 1.60, 95% CI 0.93-2.27, I2 60.2%). Similarly, analyses including only studies that adjusted measures of effect for confounders showed no association between vitamin D status and death. However, when the analysis included studies without adjustments for confounding factors, the RR was 1.51 (95% CI 1.28-1.74, I2 0.0%), suggesting that confounders may have led to many observational studies incorrectly estimating the association between vitamin D status and mortality in patients with COVID-19. Deficient vitamin D levels were not associated with increased mortality rate in patients with COVID-19 when the analysis included studies with adjustments for confounders. Randomized clinical trials are needed to assess this association.