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ABSTRACT Statins are among the most widely prescribed medicines in the world and have proved their value in reducing cardiovascular events and mortality. Many patients report adverse effects that lead to interruption of treatment. This review aims to individualize statin treatment, considering efficacy for reducing cardiovascular risk and safety, in the setting of specific diseases, to minimize the side effects and improve compliance. We gathered evidence that may help clinicians to choose specific statins in different clinical situations, such as the risk of new diabetes, chronic kidney disease, liver disease, human immunodeficiency virus infection, organ transplant, heart failure and elderly people. Efficacy of statins is well established in a large number of clinical conditions. Therefore, main objective is to revise statin in specific clinical settings, based on pharmacokinetics, safety, drug metabolism and interactions to provide the best choice in different clinical scenarios.

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ABSTRACT Metabolomics uses several analytical tools to identify the chemical diversity of metabolites present in organisms. These metabolites are low molecular weight molecules (<1500 Da) classified as a final or intermediary product of metabolic processes. The application of this omics technology has become prominent in inferring physiological conditions through reporting on the phenotypic state; therefore, the introduction of metabolomics into clinical studies has been growing in recent years due to its efficiency in discriminating pathophysiological states. Regarding endocrine diseases, there is a great interest in verifying comprehensive and individualized physiological scenarios, in particular for growth hormone deficiency (GHD). The current GHD diagnostic tests are laborious and invasive and there is no exam with ideal reproducibility and sensitivity for diagnosis neither standard GH cut-off point. Therefore, this review was focussed on articles that applied metabolomics in the search for new biomarkers for GHD. The present work shows that the applications of metabolomics in GHD are still limited, since the little complementarily of analytical techniques, a low number of samples, GHD combined to other deficiencies, and idiopathic diagnosis shows a lack of progress. The results of the research are relevant and similar; however, their results do not provide an application for clinical practice due to the lack of multidisciplinary actions that would be needed to mediate the translation of the knowledge produced in the laboratory, if transferred to the medical setting.

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ABSTRACT Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.

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ABSTRACT Objective: Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. Subjects and methods: A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. Results: Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. Conclusions: Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

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ABSTRACT Objective There is evidence demonstrating that cardiovascular diseases (CVD) manifesting during adulthood result from an intense interaction among risk factors that may have originated during childhood and adolescence. To compare the prevalence and clustering of cardiovascular risk factors in Brazilian schoolchildren with a 15-year interval between samples. Subjects and methods A cross-sectional analysis based on the scores for cardiovascular risk factors was used to investigate 1,232 Brazilian schoolchildren of both sexes aged 12 to 18 years. The data of 596 schoolchildren of the 2000 sample were compared to those of 636 schoolchildren of the 2015 sample. Results The prevalence of physical inactivity and abdominal obesity increased exponentially in both sexes from 2000 to 2015. The score for the clustering of cardiovascular risk factors showed that in 2000 the adolescents were exposed to 1 cardiovascular risk factor (31.7%), while in 2015 the greatest percentage was assigned to the category of 3 or more cardiovascular risk factors (34.9%), p < 0.001. Conclusion The present results demonstrate a high prevalence of exposure to health risk behaviors of the adolescents studied over time. Considering the presence of modifiable risk factors, preventive measures regarding life style are essential.

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ABSTRACT Objective The aim was to describe the clinical features of patients with ectopic Cushing syndrome (ECS) from Colombia and compare these findings with other series to provide the best management for these patients. Materials and methods Records of patients with ECS from 1986 to 2017 were retrospectively reviewed; patients with a diagnosis of adrenal or pituitary Cushing syndrome (CS) were excluded. Results Fourteen patients with ECS were analyzed in this study. The mean age was 54.4 (SD 17.1) years, and the female to male ratio was 1.33:1. Regarding the etiology of ECS, four patients had lung carcinoids (28.6%), three had small-cell lung carcinoma (21.4%), three had pancreatic neuroendocrine tumors (21.4%), one had medullary thyroid cancer (7.1%), one had non-metastatic pheochromocytoma (7.1%), one had metastatic thymoma (7.1%) and one patient had an occult source of ACTH (7.1%). The most common clinical features at presentation were moon-face, muscle weakness, diabetes mellitus and hypertension. Hyperpigmentation was present in 36% of patients, and 12 patients had hypokalemia with a mean value of 2.3 mEq/L (SD 0.71). The median basal cortisol, 24-hour urinary free cortisol (UFC) and ACTH were 30.5 ug/dL (IQR 21-59 ug/dL), 2,600 ug/24 h (IQR 253-6,487 ug/24 h) and 91 pg/mL (IQR 31.9-141.9), respectively. Thirteen patients (92.8%) had the site of the primary lesion identified. Six patients had undergone a surgical intervention to address the primary tumor. Resection was curative in 28.5% of patients. Death occurred in 57.1% of patients, and the median overall survival was 27 months. Intrathoracic tumors had the most aggressive behavior. Conclusions ECS is a rare disease; however, it is associated with high morbidity and mortality. A rapid intervention supported by an interdisciplinary group is required to improve overall survival and quality of life

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ABSTRACT Objective To evaluate the association between MetS, its components and insulin resistance (IR) with 25(OH)D and hsCRP. The moderator role of 25(OH)D in the association of MetS, its diagnostic components and IR with hsCRP were also explored. Materials and methods A cross-sectional study (2014/2015) with a population-based cohort in Southern Brazil (n = 605). Metabolic syndrome (MetS) diagnosis was defined based on the Joint Interim Statement, while the Homeostasis Model Assessment of insulin resistance (IR) (HOMA-IR) was used for determining IR. Serum concentrations of 25-hydroxy vitamin D [25(OH)D] (ng/mL) and high sensitivity C-reactive protein (hsCRP) (mg/L) were evaluated following standard protocols. 25(OH)D was categorized as sufficiency (>30 ng/mL), insufficiency (20-30 ng/mL) or deficiency (<20 ng/mL) to test its moderator role. Multiple linear regression was used to test the associations. The results were adjusted for possible confounders. Results and discussion Hypertriglyceridemia and IR were associated with lower 25(OH)D concentrations. However, except for systolic blood pressure, other MetS components and IR were associated with higher hsCRP. The association between elevated waist circumference (WC) and hsCRP was moderated by the 25(OH)D concentrations. The hsCRP median concentrations were more than two times higher among those with elevated WC and 25(OH)D insufficiency or deficiency. In this study, inadequate concentrations of 25(OH)D increased the adverse relationship between elevated WC and inflammation. 25(OH)D concentrations could be incorporated into the clinical protocols for monitoring individuals with abdominal obesity to identify those at a higher risk of complications.

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ABSTRACT Objective The aim of the study was to assess the long-term impact of laparoscopic sleeve gastrectomy (LSG) on lipid profile, uric acid level and metabolic syndrome. Materials and methods A prospective study was performed between 2009-2014, evaluating long-term percentage of excesso body mass index loss (%EBMIL), lipid profile, uric acid level and metabolic syndrome. Results Overall sixty subjects were followed-up. %EBMIL increased significantly, reaching a maximum (86,9 ± 6,3%) at 5 years post-LSG. Therapeutic success rate (%EBMIL ≥ 60%) was 80% at 5 years. The triglyceride level decreased significantly (148 ± 72.1 mg/dL baseline vs 130.7 ± 57.5 mg/dL at 1 month vs 110.7 ± 42.6 mg/dL at 3 months vs 92.5 ± 35.2 mg/dL at 1 year vs 84.2 ± 32.3 mg/dL at 5 years; p < 0.05 for all). HDL-cholesterol increased and uric acid decreased significantly in the first year postoperatively, remaining stable afterwards (46.9 ± 12.3 mg/dL baseline vs 47.4 ± 10 mg/dL at 1 month vs 49.8 ± 9.3 mg/dL at 3 months vs 55.4 ± 10.2 mg/dL at 1 year; p < 0.05 for all for HDL-cholesterol and 6.4 ± 2 mg/dL baseline vs 6 ± 1.7 mg/dL at 1 month vs 5.2 ± 1.3 mg/dL at 3 months vs 4.8 ± 1 mg/dL at 1 year; p < 0.05 for all for uric acid). The prevalence of metabolic syndrome decreased from 66.7% baseline to 8.3% at 5 years postoperatively (p < 0.01). Conclusions LSG was effective in terms of %EBMIL and metabolic traits improvement for Romanian patients.

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ABSTRACT Objective The aim of this study was to translate and cross-culturally adapt the Insulin Delivery System Rating Questionnaire (IDSRQ) for Brazilian users. Validation and reliability analysis of measures were also performed. Materials and methods Methodological study comprising the following stages: forward translation, synthesis, back-translation, assessment by Expert Committee, pre-test and validation. International guidelines for translation and cross-cultural adaptation of measurement tools were followed. Validation data provided information about reliability (internal consistency, test-retest) and construct validity of the IDSRQ. Results Content validation by Experts’ assessment was successful, with a mean Content Validity Index of 0.87 (±0.2). The IDSRQ validation study involved 113 T1DM patients, 46% male, mean age 32.61 (±12.59) years and mean age at diagnosis of diabetes of 17.51 (±12.41). The scale presented good internal consistency (Cronbach’s alpha =0.786). The reliability analysis of the instrument was conducted by calculating the Intra-class Correlation Coefficient 0.885 (0.834-0.921), which indicated adequate concordance in all measures. Conclusion The translated and cross-culturally adapted Brazilian Portuguese version of the IDSRQ may be used to assess health-related quality of life (HRQOL) and treatment preferences for insulin delivery systems in T1DM Brazilian patients.

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ABSTRACT Objective: Evaluate ferritin levels in children and adolescents with type 1 diabetes mellitus and its relation to diabetic microvascular complications, and metabolic control. Subjects and methods: This study included 180 children and adolescents with type 1 diabetes mellitus (T1DM) with a mean age of 14.9 ± 3.1 years and 180 apparently normal children matched for age and sex (control group). All children were evaluated with full history taking, thorough clinical examination, laboratory assessment of high-sensitivity C-reactive protein and hemoglobin A1c (HbA1c), and evaluation of the presence of microvascular complications. Serum ferritin levels were measured using electrochemiluminescence immunoassay. The patients were divided into two groups according to the presence or absence of microvascular complications. Results: Serum ferritin levels were significantly higher in patients with T1DM in both groups compared with healthy controls (p < 0.001). Additionally, patients with microvascular complications had higher serum ferritin concentrations than those without microvascular complications (p < 0.001). Patients with microalbuminuria showed higher ferritin levels compared with patients without microalbuminuria (p < 0.05). Stepwise regression analysis revealed that levels of HbA1c and urinary albumin excretion were independently related to ferritin levels (p < 0.001 for both). On receiver operating characteristic (ROC) curve analysis, a ferritin cutoff value of 163.6 ng/mL differentiated patients with microvascular complications from those without microvascular complications with a sensitivity of 92.1% and specificity of 93.4%. Conclusion: Serum ferritin levels are elevated in T1DM, particularly in patients with microvascular complications.

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ABSTRACT Objective: To determine the prevalence of vitamin D deficiency (VDD) in exclusively breastfed infants at the Aga Khan University Hospital Nairobi, Kenya (AKUHN). The relationships between 25-hydroxyvitamin D; 25OHD, parathyroid hormone (PTH), maternal vitamin D supplementation, and sunlight exposure were also determined. Subjects and methods: Blood from 98 infants was assayed for 25OHD, calcium, phosphate, and PTH. Socio-demographic and clinical characteristics were analyzed using descriptive statistics and inferential analysis (p < 0.05). Results: The prevalence of VDD (25OHD <12 ng/mL), vitamin D insufficiency (VDI, 25OHD 12-20 ng/mL) and vitamin D sufficiency (VDS, 25OHD >20 ng/mL) was 11.2% (95% CI 8.0%-14.4%), 12.2% (95% CI 8.9%-15.5%), and 76.5% (95% CI 72.3%-80.8%) respectively. There was no difference in the mean age, head circumference, length, or weight of infants in VDD, VDI, and VDS groups. PTH was elevated when 25OHD was <12 ng/mL and normal when 25OHD was between 12-20 ng/mL. 25OHD and PTH were normal in infants whose mothers received vitamin D supplements. Infants who received <30 minutes/day of exposure to sunlight were 5 times more likely to have VDI than infants who received ≥30 minutes/day (p = 0.042). Conclusions: The prevalence of VDD in exclusively breastfed infants at AKUHN is low. The current national policy that recommends exclusive breastfeeding of infants in the first 6 months of life appears to be effective in staving off vitamin D deficiency but those infants with < 30 minutes sunlight exposure may benefit from low dose supplemental vitamin D during times of low sunlight exposure.

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ABSTRACT Objective: Ultrasonography (US) is the most accurate and cost-effective imaging method in diagnosis of thyroid nodules. A practical thyroid imaging reporting and data system (TIRADS) for thyroid nodules has been proposed to classify nodules of the thyroid gland to solve the problem of nodule selection for fine needle aspiration cytology (FNAC). Real-time elastography and strain ratio (SR) is a method used to assess the stiffness and predict the malignancy of thyroid nodules. The objective of this study was to assess the role of elastography and SR and the TIRADS scoring system in discriminating malignant from benign thyroid nodules. Materials and methods: From 2015 to 2018 at Cairo University Hospital, a series of 409 patients with thyroid nodules was referred to undergo thyroid ultrasound. Categorization of each nodule according to the TIRADS ranged from 1 to 5. The qualitative elastography score and semiquantitative SR of the nodules were evaluated. Final diagnosis was done by either postthyroidectomy histopathological examination or US-guided FNAC. Results: Our study included 409 patients with thyroid nodules. Their mean age was 39 ± 10 SD; 36 were males and 373 were females. There were 22 malignant nodules and 387 benign nodules. There were statistical differences between benign and malignant nodules regarding TIRADS classification, SR, anteroposterior/transverse ratio, degree of echogenicity, border, presence of calcification, and absence of halo sign (P < 0.001). The elastic properties of thyroid nodules proved to be a good discriminator between malignant and benign nodules (P- < 0.001) at a cut off value of > 2.32 with 95.2% sensitivity and 86.5% specificity. For every unit increase in SR, the risk of malignancy increased by nearly 2 times. Patients with irregular borders had nearly 17 times increased risk of malignancy than those with regular borders. Conclusion: Elastography and SR proved to be of high significant value in discriminating benign from malignant nodules, so we recommend adding it to the TIRADS classification.

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ABSTRACT Objective: The relationship of thyroid dysfunction and autoimmunity with breast cancer (BC) continues to be contentious. The primary aim of this study was to estimate the prevalence of thyroid dysfunctions and autoimmunity in BC patients, and the secondary aims were to investigate the relationship of thyroid dysfunction with the clinicopathological profile of and therapy received by BC patients. Materials and methods: This was a single-center prospective case-control study (March 2015-May 2017). Women with BC (n = 191), age-matched healthy controls (n = 166) and malignant controls (patients with cervical cancer, n = 87) were enrolled. Basal serum free thyroxin (fT4), thyrotropin (TSH) and anti-thyroid peroxidase (TPO) antibody levels were measured in all three groups; fT4, TSH and TPO measures were repeated after chemotherapy and at the 1-year follow-up (one year after diagnosis) in the BC patients. Results: The prevalence of overall hypothyroidism and autoimmunity (p = 0.106) did not differ significantly between the three groups, but the rate of clinical hypothyroidism was significantly higher in the BC group than in the healthy control group and the malignant control group (12.2% vs. 3.0% vs. 4.6%, respectively; p = 0.001). BC patients had significantly lower mean basal TSH concentrations than the healthy controls (p = 0.017). The postchemotherapy TSH concentrations were significantly lower (p = 0.001), and the fT4 concentrations were higher, albeit not significantly (p = 1.00), than the respective basal concentrations. The reverse was true for the follow-up values, in which the TSH (p = 1.00) values were higher and the fT4 (p = 0.03) concentrations were lower than the respective basal concentrations. An additional 6% of the BC patients developed clinical hypothyroidism during follow-up. Hypothyroid (p = 0.02) and TPO-positive (p = 0.004) patients had significantly smaller tumors, but their other clinicopathological features were comparable to those without thyroid dysfunction. Conclusions: The prevalence of clinical hypothyroidism requiring thyroxine replacement was significantly high in BC patients and increased further during follow-up. Hence, BC patients should be considered a high-risk group that should receive routine screening for hypothyroidism.

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ABSTRACT Objective: Although the prognostic role of BRAFV600E mutation in papillary thyroid carcinoma (PTC) is controversial, the American Thyroid Association (ATA) includes the mutational status in their risk stratification system. To evaluate the impact of the BRAFV600E mutation status on PTC risk stratification. Subjects and methods: PTC patients attending a university-based hospital who had the analysis of the BRAFV600E mutation were included. Persistent disease was defined as the presence of biochemical or structural disease. The performance of the ATA risk stratification system on predicting persistent disease with or without the BRAFV600E mutation status information was evaluated. Results: Of the 134 patients evaluated, 44 (32.8%) carried BRAFV600E mutation. The median tumor size was 1.7 cm (P25-75 1.0-3.0), 64 (47.8%) patients had lymph node, and 11 (8.2%) distant metastases. According to the ATA risk stratification system, patients were classified as low, intermediate, and high risk in 55 (41%), 59 (44%), and 20 (14%) patients, respectively. The data on BRAFV600E mutation reclassified 12 (8.9%) patients from low to intermediate risk. After a median follow-up of 8.5 years, the prevalence of persistent disease was similar in patients with and without BRAFV600E mutation (P = 0.42). Multivariate analysis failed to demonstrate an association between the BRAFV600E mutation and persistent disease status (RR 0.96; 95%CI 0.47-1.94). Notably, none of the patients reclassified from low to intermediate risk showed persistent disease on follow-up. Conclusion: Inclusion of BRAFV600E mutational status has a limited impact on risk stratification and does not add to the prediction of outcomes in PTC patients.

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ABSTRACT Objective: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. Subjects and methods: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. Results: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment–insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). Conclusion: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

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ABSTRACT Objective: The intermediate-risk (IR) category includes tumors with different degrees of aggression. We aimed to identify the risk factors associated with unfavorable response to initial treatment and compare the effect of low/high radioactive iodine (RAI) therapy. Subjects and methods: A total of 614 IR patients were selected from a database, during 1972-2015. All patients underwent total thyroidectomy and RAI therapy and were reclassified after 12-18 months into the favorable (complete/indeterminate) response group and the unfavorable (biochemical/incomplete structural) response group. A total of 92 patients were assessed for late response (mean: 9.19 ± 5.73 years). Age, gender, tumor size, histology, multifocality, vascular invasion, extrathyroidal extension, presence and number of lymph node metastasis, and stimulated thyroglobulin at ablation (sTg) were evaluated. Results: Mean age at diagnosis was 41.47 ± 15.81 years, and 83.6% of the patients were female. Within 12-18 months after initial therapy, unfavorable response was detected in 41.2% of the patients and was associated, in multivariate analysis, with lymph node metastasis (p = 0.041; odds ratio [OR] = 1.9), presence of more than five metastatic lymph nodes (p = 0,017; OR = 2.6), and sTg > 10 ng/mL (p = 0.005; OR = 10.0). For patients with a longer follow-up, sTg >10 ng/mL was associated with unfavorable response (p = 0.002; OR = 6.8). A higher RAI dose was not related to better prognosis at the end of the follow-up. Conclusion: A sTg level of >10 ng/mL and lymph node metastasis were associated with an unfavorable response 12-18 months after initial treatment. A RAI dose below 150 mCi was proven sufficient to treat IR patients.

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ABSTRACT Objective: This study investigated whether ELABELA plays a role in the differential diagnosis of benign and malignant lesions of the thyroid gland. Subjects and methods: Of the 87 patients included in the study, 12 had undergone surgery for benign thyroid diseases, 30 had papillary thyroid cancer without invasion and/or lymph node metastasis in the surrounding tissues in the pathology report, and 45 had papillary thyroid cancer with invasion and/or lymph node metastasis in the surrounding tissues. Results: In the macrocarcinoma group, the proportion of patients with severe ELABELA staining (61.1%) was higher than that in the adenoma (50%) and microcarcinoma (23.8%) groups, while the proportion of those with mild to moderate staining was lower (p < 0.001). In the microcarcinoma group, the proportion of patients with severe staining was lower than that in the adenoma group, while the proportion of those with mild to moderate staining was higher (p < 0.001). In papillary thyroid carcinomas, the rates of moderate and severe staining in the classical variant, mild staining in the follicular variant, severe staining in the classical + follicular variant, and severe staining in the oncocytic variant were higher. Conclusion: To the best of our knowledge, this study is the first to be conducted on this subject. In this study, ELABELA was not found to be significant in the differential diagnosis of benign and malignant lesions of the thyroid gland. In papillary thyroid carcinomas, severe ELABELA staining patterns were more common in macrocarcinoma patients than in microcarcinoma patients.

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ABSTRACT Objective: To obtain data about the evaluation of thyroid nodules (TNs) in the northeastern of the State of São Paulo, compared by health care type, and measure the performance of cytology as a screening test for thyroid cancer (TC). Subjects and methods: We collected data of 597 patients treated in the Brazilian public health care system (SUS), supplementary health (SH) and in private health system (PHS) in 2014. A total of 803 TNs were aspirated, and 125 patients underwent surgery. Results: The distribution of all cytologic results according to the Bethesda system was: I, 135 (16.8%); II, 475 (59.2%); III, 107 (13.3%); IV, 32 (4.0%); V, 20 (2.5%); VI, 34 (4.2%). The time between cytologic analysis and surgery was longer in the SUS than in the SH for TNs in general (p < 0.001) and for TNs with Bethesda V and VI cytology (p = 0.01). The sizes of the TNs and resected malignant TNs was larger in the SUS than in the SH (p = 0.001 and p = 0.02, respectively). The number of PHS surgeries was too small and was not compared. The prevalence of TC was 9.2% and 23.6% of them were treated in the SUS. Cytology showed a 93.6% sensitivity, 95.8% specificity, and 94.7% accuracy when Bethesda III and IV were excluded. Conclusion: Cytology was a good screening test for TC categories Bethesda II, V, and VI. The differences between the SUS and SH indicate a need for improved access to consultations and specialized tests in the SUS.

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ABSTRACT Objective: We aimed to investigate the role of DIO2 polymorphisms rs225014 and rs12885300 in Graves’ disease patients, mainly for controlling body weight following treatment. Subjects and methods: We genotyped 280 GD patients by the time of diagnosis and 297 healthy control individuals using a TaqMan SNP Genotyping technique. We followed up 141 patients for 18.94 ± 6.59 months after treatment. Results: There was no relationship between the investigated polymorphisms with susceptibility to GD and gain or loss of weight after GD treatment. However, the polymorphic inheritance (CC+CT genotype) of DIO2 rs225014 was associated with a lower body weight variation after GD treatment (4.26 ± 6.25 kg) when compared to wild type TT genotype (6.34 ± 7.26 kg; p = 0.0456 adjusted for the follow-up time). This data was confirmed by a multivariate analysis (p = 0.0138) along with a longer follow-up period (p = 0.0228), older age (p = 0.0306), treatment with radioiodine (p-value = 0.0080) and polymorphic inheritance of DIO2 rs12885300 (p = 0.0306). Conclusion: We suggest that DIO2 rs225014 genotyping may have an auxiliary role in predicting the post-treatment weight behavior of GD patients.

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ABSTRACT Objective: The aim of this cross-sectional study was to estimate the prevalence of XLH in Paraná, a state in southern Brazil, and report the clinical features and complications of the disease. Materials and methods: We invited all endocrinologists (n = 205), nephrologists (n = 221), orthopedic surgeons (n = 1020), and pediatricians (n = 1000) in Paraná to fill out an electronic survey with information on patients with X-linked hypophosphatemia (XLH), and searched the records of the state's health department for all calcitriol prescriptions in 2018. Results: In all, 244 (10%) specialists responded to the email, of whom 18 (7.4%) reported to be taking care of patients with XLH and answered the online survey. A total of 57 patients with XLH were identified (prevalence 5 per million inhabitants). The median age at diagnosis was 22 years, and 42.2% were children and adolescents. Fifteen patients had genetic testing showing a PHEX mutation. Overall, 91.2% had bone deformities, 30.8% had a history of fragility fractures, and 22.4% had renal complications. Conclusion: This study demonstrated a prevalence of XLH of 5 cases per million inhabitants in the state of Paraná, a rate lower than the one reported in other countries. Manifestations of renal calcification and bone fragility were frequent among the patients. This is the first epidemiological study evaluating the prevalence and clinical presentation of XLH in Latin America.

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ABSTRACT Objective: The objective of the study was to develop an association between clinicopathologic and sonographic features of patients with papillary thyroid microcarcinoma and the prevalence of lymph node metastasis. Subjects and methods: Clinicopathologic and sonographic features of 415 patients of papillary thyroid microcarcinoma with (n = 102) or without (n = 313) lymph node metastasis were retrospectively reviewed. The thickness of the lymph node ≥ 6 mm with intra-lymph nodal occupying lesions considered lymph node metastasis. Also, it was considered metastasis if lymph node perfusion or blood flow defect was found with any thickness size. Univariate following multivariate analysis was performed for the prediction of sonographic features and clinicopathologic factors for the prevalence of lymph node metastasis. Results: Male gender ( p = 0.041), age < 45 years ( p = 0.042), preoperative calcitonin > 65 pg/ mL ( p = 0.039), nodule size > 5 mm in diameter ( p = 0.038), bilaterality ( p = 0.038), tumor capsular invasion ( p = 0.048), cystic change ( p = 0.047), and hyper vascularity ( p = 0.049) of thyroid nodules were associated with lymph node metastasis. Also, thyroid nodules 5 mm and more in diameter may have high aggressiveness. Conclusion: These data helped the surgeon for individualized treatment in thyroid carcinoma and avoid unnecessary prophylactic surgery of the lymph node.

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ABSTRACT Objective: We conducted a study to examine the association of endothelial dysfunction and oxidative stress with uric acid levels in patients of metabolic syndrome. Subjects and methods: One hundred and two patients of Metabolic Syndrome (International Diabetes Federation definition) were included in the study. Anthropometric measurements, serum uric acid levels, fasting blood sugar levels and lipid levels, as well as malondialdehyde and reactive nitrogen intermediates were measured after an 8-hour fasting period. Flow mediated vasodilation (FMD) of the brachial artery was measured and endothelial dysfunction was defined as an increase in diameter < 10% post compression. Results: A total of 102 patients were included in the study. Mean uric acid level was 5.49 ± 1.61 mg%. A total of 59 patients in the study had endothelial dysfunction, defined by an abnormal FMD. Patients with an abnormal FMD had higher levels of serum uric acid which was statistically significant (p value = 0.010). Serum RNI and MDA levels were negatively correlated with uric acid, but did not reach statistical significance. Patients with an abnormal FMD had a lower RNI level, but this did not reach statistical significance. Serum MDA levels were significantly higher in patients with an abnormal FMD (p value = 0.038). Conclusions: Uric acid was significantly associated with endothelial dysfunction in patients with metabolic syndrome in our study. It was inversely correlated with serum RNI and MDA levels, but this did not reach statistical significance.

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ABSTRACT Oubjective: To assess the implications of changing the cutoff level of TSH from 10 to 6 mIU/L. Subjects and methods: The study population was constituted by 74.123 children screened for congenital hypothyroidism by the National Screening Program in Santa Catarina, from March 2011 to February 2012. The cutoff of TSH was 6 mIU/L. If TSH between 6-10 mIU/L, the newborn was recalled for a second TSH measurement on filter paper. If TSH > 6 mIU/L in the second sample, the child was sent for medical evaluation. In children with normal topic thyroid, levothyroxine was suspended for 1 month at the age of 3 years for identification of the etiology and evaluation of the need to continue treatment. Results: Among the children screened, 435 were recalled for presenting TSH between 6 and 10 mIU/L in the first sample, 28 remained TSH > 6 mIU/L in the second sample. Among these, 11 had a final diagnosis of dyshormonogenesis, two of ectopic thyroid, two of thyroid hypoplasia and one of transient hypothyroidism. Ten children presented normal TSH levels on the first medical evaluation and two lost follow-up. Conclusion: A decrease in the TSH cutoff level from 10 to 6 mIU/L in a neonatal screening program for congenital hypothyroidism reduced the number of false-negative results, increasing the sensitivity of the test, but increased the number of false-positive results and recalls. Since a TSH cutoff level of 6 mIU/L detects thyroid function abnormalities requiring treatment, the adoption of this cutoff level is justified.

Resumo em Inglês:

ABSTRACT Objective: This study aimed to explore the patterns of radioactive iodine (RAI) use for differentiated thyroid cancer (DTC) in Brazil over the past 20 years. Materials and methods: A retrospective analysis of the DTC-related RAI prescriptions, from 2000 to 2018, retrieved from the Department of Informatics of the Unified Health System (Datasus) and National Supplementary Health Agency (ANS) database was performed. RAI activities prescriptions were re-classified as low (30-50 mCi), intermediate (100 mCi), or high activities (>100 mCi). Results: The number of DTC-related RAI prescriptions increased from 0.45 to 2.28/100,000 inhabitants from 2000 to 2015, declining onwards, closing 2018 at 1.87/100,000. In 2018, population-adjusted RAI prescriptions by state ranged from 0.07 to 4.74/100,000 inhabitants. Regarding RAI activities, in the 2000 to 2008 period, the proportion of high-activities among all RAI prescriptions increased from 51.2% to 74.1%. From 2009 onwards, there was a progressive reduction in high-activity prescriptions in the country, closing 2018 at 50.1%. In 2018, the practice of requesting high-activities varied from 16% to 82% between Brazilian states. Interestingly, variability of RAI use do not seem to be related to RAI referral center volume nor state socio-economic indicators. Conclusion: In recent years, there has been a trend towards the lower prescription of RAI, and a reduction of high-activity RAI prescriptions for DTC in Brazil. Also, significative inter-state and inter-institutional variability on RAI use was documented. These results suggest that actions to advance DTC healthcare quality surveillance should be prioritized.