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Archives of Endocrinology and Metabolism, Volume: 62, Número: 1, Publicado: 2018
  • The Janus faces of thyroid carcinoma Editorial

    Martins, João Roberto M.
  • (Epi) Genetics and the complexity of diabetes mellitus Editorial

    Corrêa-Giannella, Maria Lúcia
  • Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort Original Article

    Domínguez, José M.; Nilo, Flavia; Martínez, María T.; Massardo, José M.; Muñoz, Sueli; Contreras, Tania; Carmona, Rocío; Jerez, Joaquín; González, Hernán; Droppelmann, Nicolás; León, Augusto

    Resumo em Inglês:

    ABSTRACT Objective We aimed to describe the presentation of papillary microcarcinoma (PTMC) and identify the clinical and histological features associated with persistence/recurrence in a Latin American cohort. Subjects and methods Retrospective study of PTMC patients who underwent total thyroidectomy, with or without radioactive iodine (RAI), and who were followed for at least 2 years. Risk of recurrence was estimated with ATA 2009 and 2015 classifications, and risk of mortality with 7th and 8th AJCC/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results We included 209 patients, predominantly female (90%), 44.5 ± 12.6 years old, 183 (88%) received RAI (90.4 ± 44.2 mCi), followed-up for a median of 4.4 years (range 2.0–7.8). The 7th and 8th AJCC/TNM system classified 89% and 95.2% of the patients as stage I, respectively. ATA 2009 and ATA 2015 classified 70.8% and 78.5% of the patients as low risk, respectively. Fifteen (7%) patients had persistence/recurrence during follow-up. In multivariate analysis, only lymph node metastasis was associated with persistence/recurrence (coefficient beta 4.0, p = 0.016; 95% CI 1.3-12.9). There were no PTMC related deaths. Conclusions Our series found no mortality and low rate of persistence/recurrence associated with PTMC. Lymph node metastasis was the only feature associated with recurrence in multivariate analysis. The updated ATA 2015 and 8th AJCC/TNM systems classified more PTMCs than previous classifications as low risk of recurrence and mortality, respectively.
  • Outcomes of patients with bone metastases from differentiated thyroid cancer Original Article

    Califano, Inés; Deutsch, Susana; Löwenstein, Alicia; Cabezón, Carmen; Pitoia, Fabián

    Resumo em Inglês:

    ABSTRACT Objective Bone metastases (BM) from differentiated thyroid cancer (DTC) are associated with poor survival rates. Due to the low frequency of this entity, we performed a multicentric retrospective study that aimed to evaluate the presentation, outcome and causes of death in this population. Subjects and methods We reviewed file records from 10 databases. BM were diagnosed by: i) biopsy and/or ii) radioiodine (RAI) bone uptake + elevated thyroglobulin (Tg) levels and/or c) bone uptake of 18-FDG in the PET-CT scan + elevated Tg levels. Results Fifty-two patients with DTC were included (44% male, mean age 54 years); 58% had papillary histology. BM were synchronous with DTC diagnosis in 46% of the participating cases. BM were symptomatic in 65% of the cases. Multiple BM were present in 65% of patients, while simultaneous metastatic disease in additional sites was found in 69%. Ninety-eight percent of patients received treatment for the BM, which included RAI therapy in 42 patients; 30 of them received cumulative RAI doses that were larger than 600 mCi 131I. The mean follow-up after a BM diagnosis was 34 months. The 2- and 5-year survival rates after diagnosis of the first BM were 64% and 38%, respectively. The status on the last evaluation was DTC-related death in 52% of the patients; 26% of them died from direct complications of BM or their treatments. Conclusion BM are usually radioiodine-refractory and are associated with a short overall survival, although most of the patients died of causes not directly related to the BM.
  • The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients Original Article

    Pirozzi, Flavio Fontes; Belini Junior, Edis; Okumura, Jessika Viviani; Salvarani, Mariana; Bonini-Domingos, Claudia Regina; Ruiz, Milton Artur

    Resumo em Inglês:

    ABSTRACT Objectives This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities.
  • Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes) Original Article

    Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Dusse, Luci Maria S; Reis, Janice Sepúlveda; Carvalho, Maria das Graças; Gomes, Karina Braga; Fernandes, Ana Paula

    Resumo em Inglês:

    ABSTRACT Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8–25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2–12.9), 8.4 (2.5–25.4), 9.1 (2.6–31.4) and 3.5 (1.4–8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.
  • Expression of miR-155, miR-146a, and miR-326 in T1D patients from Chile: relationship with autoimmunity and inflammatory markers Original Article

    García-Díaz, Diego F.; Pizarro, Carolina; Camacho-Guillén, Patricia; Codner, Ethel; Soto, Néstor; Pérez-Bravo, Francisco

    Resumo em Inglês:

    ABSTRACT Objective The aim of this research was to analyze the expression profile of miR-155, miR-146a, and miR-326 in peripheral blood mononuclear cells (PBMC) of 47 patients with type 1 diabetes mellitus (T1D) and 39 control subjects, as well as the possible association with autoimmune or inflammatory markers. Subjects and methods Expression profile of miRs by means of qPCR using TaqMan probes. Autoantibodies and inflammatory markers by ELISA. Statistical analysis using bivariate correlation. Results The analysis of the results shows an increase in the expression of miR-155 in T1D patients in basal conditions compared to the controls (p < 0.001) and a decreased expression level of miR-326 (p < 0.01) and miR-146a (p < 0.05) compared T1D patients to the controls. miR-155 was the only miRs associated with autoinmmunity (ZnT8) and inflammatory status (vCAM). Conclusion Our data show a possible role of miR-155 related to autoimmunity and inflammation in Chilean patients with T1D.
  • Increased insulin sensitivity in individuals with neurofibromatosis type 1 Original Article

    Martins, Aline Stangherlin; Jansen, Ann Kristine; Rodrigues, Luiz Oswaldo Carneiro; Matos, Camila Maria; Souza, Marcio Leandro Ribeiro; Miranda, Débora Marques; Rezende, Nilton Alves de

    Resumo em Inglês:

    ABSTRACT Objects To compare insulin resistance (IR) and metabolic aspects of patients with neurofibromatosis type 1 (NF1) and individuals without the disease. Subjects and methods Forty patients with NF1 were matched by sex, age, and body mass index (BMI) to 40 controls from the community. Blood samples were collected for biochemical assessment. Homeostasis model assessment adiponectin (HOMA-AD), Homeostasis model assessment insulin resistance (HOMA-IR), and adiponectin/leptin ratio (ALR) were used to identify IR. Results The median HOMA-IR values were similar between the groups. However, the HOMA-AD value was significantly lower and the ALR significantly higher in the NF1 group. Fasting blood glucose (FBG), leptin, and visfatin levels of patients with NF1 were significantly lower, although adiponectin levels were significantly higher than those in the controls. Fasting insulin and blood glucose levels 2 hours after administration of 75 g of dextrose, glycated hemoglobin, and resistin showed no significant differences between groups. The HOMA-AD correlated with BMI, FBG, blood glucose levels 2 hours after administration of 75 g of dextrose, fasting insulin, glycated hemoglobin, adiponectin, leptin, visfatin, ALR, and HOMA-IR. The ALR correlated with BMI leptin, visfatin, and adiponectin. Conclusions Lower levels of FBG, leptin, visfatin, and HOMA-AD, and higher adiponectin levels and ALR may be related to increased insulin sensitivity and lower occurrence of type 2 diabetes mellitus in patients with NF1
  • Higher fiber intake is associated with lower blood pressure levels in patients with type 1 diabetes Original Article

    Beretta, Mileni Vanti; Bernaud, Fernanda R.; Nascimento, Ciglea; Steemburgo, Thais; Rodrigues, Ticiana C.

    Resumo em Inglês:

    ABSTRACT Objective The present investigation sought to evaluate the potential association between dietary fiber intake and blood pressure (BP) in adult patients with type 1 diabetes (T1D). Subjects and methods A cross-sectional study was carried out in 111 outpatients with T1D from Porto Alegre, Brazil. Patients were predominantly male (56%) and white (88%), with a mean age of 40 ± 10 years, diabetes duration of 18 ± 9 years, BMI 24.8 ± 3.85 kg/m2, and HbA1c 9.0 ± 2.0%. After clinical and laboratory evaluation, dietary intake was evaluated by 3-day weighed-diet records, whose reliability was confirmed by 24-h urinary nitrogen output. Patients were stratified into two groups according to adequacy of fiber intake in relation to American Diabetes Association (ADA) recommendations: below recommended daily intake (< 14g fiber/1000 kcal) or at/above recommended intake (≥ 14g/1000 kcal). Results Patients in the higher fiber intake group exhibited significantly lower systolic (SBP) (115.9 ± 12.2 vs 125.1 ± 25.0 mmHg, p = 0.016) and diastolic blood pressure (DBP) (72.9 ± 9.2 vs 78.5 ± 9.3 mmHg, p = 0.009), higher energy intake (2164.0 ± 626.0 vs 1632.8 ± 502.0 kcal, p < 0.001), and lower BMI (24.4 ± 3.5 vs 26.2 ± 4.8, p = 0.044). Linear regression modelling, adjusted for age, energy intake, sodium intake, and BMI, indicated that higher fiber intake was associated with lower SBP and DBP levels. No significant between-group differences were observed with regard to duration of diabetes, glycemic control, insulin dosage, or presence of hypertension, nephropathy, or retinopathy. Conclusion We conclude that fiber consumption meeting or exceeding current ADA recommendations is associated with lower SBP and DBP in patients with T1D.
  • Influence of maternal weight gain on birth weight: a gestational diabetes cohort Original Article

    Mastella, Livia S.; Weinert, Letícia S.; Gnielka, Vanessa; Hirakata, Vânia N.; Oppermann, Maria Lúcia R.; Silveiro, Sandra P.; Reichelt, Angela J.

    Resumo em Inglês:

    ABSTRACT Objective Our objective was to evaluate gestational weight gain (GWG) patterns and their relation to birth weight. Subjects and methods We prospectively enrolled 474 women with gestational diabetes mellitus (GDM) at a university hospital (Porto Alegre, Brazil, November 2009-May 2015). GWG was categorized according to the 2009 Institute of Medicine guidelines; birth weight was classified as large (LGA) or small (SGA) for gestational age. Adjusted relative risks (aRRs) and 95% confidence intervals (95% CIs) were determined. Results Adequate GWG occurred in 121 women [25.5%, 95% CI: 22, 30%]; excessive, in 180 [38.0%, 95% CI: 34, 43%]; and insufficient, in 173 [36.5%, 95% CI: 32, 41%]. In women with normal body mass index (BMI), the prevalence of SGA was higher in those with insufficient compared to adequate GWG (30% vs. 0%, p < 0.001). In women with BMI ≥ 25 kg/m2, excessive GWG increased the prevalence of LGA [aRR 2.58, 95% CI: 1.06, 6.29] and protected from SGA [aRR 0.25, 95% CI: 0.10, 0.64]. Insufficient vs. adequate GWG did not influence the prevalence of SGA [aRR 0.61, 95% CI: 0.31, 1.22]; insufficient vs. excessive GWG protected from LGA [aRR 0.46, 95% CI: 0.23, 0.91]. Conclusions One quarter of this cohort achieved adequate GWG, indicating that specific ranges have to be tailored for GDM. To prevent inadequate birth weight, excessive GWG in women with higher BMI and less than recommended GWG in normal BMI women should be avoided; less than recommended GWG may be suitable for overweight and obese women.
  • Assessing endocrine and immune parameters in human immunodeficiency virus-infected patients before and after the immune reconstitution inflammatory syndrome Original Article

    Rateni, Liliana; Lupo, Sergio; Racca, Liliana; Palazzi, Jorge; Ghersevich, Sergio

    Resumo em Inglês:

    ABSTRACT Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p < 0.05) in IRIS-P than in non-IRIS-P (3.9 ± 1.0 pg/mL and 461.0 ± 84.4 pg/mL, respectively) BT. Mean T4 plasma level significantly decreased in both groups of patients after treatment (p < 0.05). In both groups cortisol levels were similar before and after ART (p > 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease.
  • Cardiovascular risk in rural workers and its relation with body mass index Original Article

    Bernhard, Joana Carolina; Dummel, Kely Lisandra; Reuter, Éboni; Reckziegel, Miriam Beatris; Pohl, Hildegard Hedwig

    Resumo em Inglês:

    ABSTRACT Objective Evaluate the propensity of cardiovascular risk in rural workers and, through the Framingham Risk Score (FRS), relate this risk with the classification of Body Mass Index (BMI). Subjects and methods This study is characterized as descriptive and exploratory, with the participation of 138 subjects, ranging between 25-73 years old. Clinical and laboratory analysis of the risk factors contained in the FRS were performed, in addition to the determination of BMI, blood pressure, smoking and physical inactivity. Results The procedures indicated a low risk of a coronary event in 10 years with 70.3% of the population. In contrast, 88.4% of the subjects were overweight. It was evidenced a risk improvement as the BMI increased, since 96.4% of high-risk cases were overweight or obese. Conclusion Results suggest larger prevalence of intermediary or high FRS for women with higher BMI, which was not observed in men.
  • A possible association between the -2518 A>G MCP-1 polymorphism and insulin resistance in school children Original Article

    Matia-García, Inés; Salgado-Goytia, Lorenzo; Ramos-Arellano, Luz Elena; Muñoz-Valle, José Francisco; Armenta-Solís, Adakatia; Garibay-Cerdenares, Olga Lilia; Ramírez, Mónica; Parra-Rojas, Isela

    Resumo em Inglês:

    ABSTRACT Objective Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the pathophysiology of insulin resistance (IR); therefore, variants in the MCP-1 gene may contribute to the development of this disease. The aim of this study was to analyze the relationship of the -2518 A>G MCP-1 (rs1024611) gene polymorphism with insulin resistance in Mexican children. Subjects and methods A cross-sectional study was performed in 174 children, including 117 children without insulin resistance and 57 children with IR, with an age range of 6-11 years. Levels for serum insulin and high-sensitivity C-reactive protein were determined. The -2518 A>G MCP-1 polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Insulin resistance was defined as a HOMA-IR in the upper 75th percentile, which was ≥ 2.4 for all children. Results Genotype frequencies of the rs1024611 polymorphism for the insulin-sensitive group were 17% AA, 48% AG and 35% GG, and the frequency of G allele was 59%, whereas frequencies for the insulin-resistant group were 12% AA, 37% AG and 51% GG, and the frequency of G allele was 69%. The genotype and allele frequencies between groups did not show significant differences. However, the GG genotype was the most frequent in children with IR. The GG genotype was associated with insulin resistance (OR = 2.2, P = 0.03) in a genetic model. Conclusion The -2518 A>G MCP-1 gene polymorphism may be related to the development of insulin resistance in Mexican children.
  • A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism Review

    Machado, Márcio Carlos; Fragoso, Maria Candida Barisson Vilares; Moreira, Ayrton Custódio; Boguszewski, César Luiz; Vieira Neto, Leonardo; Naves, Luciana A.; Vilar, Lucio; Araújo, Luiz Antônio de; Musolino, Nina Rosa Castro; Miranda, Paulo Augusto C.; Czepielewski, Mauro A.; Gadelha, Monica R.; Bronstein, Marcello Delano; Ribeiro-Oliveira Jr., Antônio

    Resumo em Inglês:

    ABSTRACT The treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.
  • Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism Guideline

    Maeda, Sergio Setsuo; Moreira, Carolina Aguiar; Borba, Victória Zeghbi Cochenski; Bandeira, Francisco; Farias, Maria Lucia Fleiuss de; Borges, João Lindolfo Cunha; Paula, Francisco José Albuquerque de; Vanderlei, Felipe Augusto Brasileiro; Montenegro, Fábio Luiz de Menezes; Santos, Rodrigo Oliveira; Ferraz-de-Souza, Bruno; Lazaretti-Castro, Marise

    Resumo em Inglês:

    ABSTRACT Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.
  • Humoral hypercalcemia of pregnancy treated with bisphosphonates Case Report

    Koren, Ronit; Neeman, Ortal; Koren, Shlomit; Benbassat, Carlos A.

    Resumo em Inglês:

    SUMMARY Hypercalcemia can be hazardous during pregnancy, most cases being due to primary hyperparathyroidism. We report a case of hypercalcemia with suppressed PTH levels necessitating treatment with bisphosphonates during pregnancy. A 38-year-old woman at the 26th week gestation was admitted because of symptomatic hypercalcemia. She did not take any medication that could influence her calcium levels. Physical examination was unremarkable. Laboratory tests on admission were: calcium 12.7 mg/dL (8.5-10.5 mg/dL), phosphorus 1.8 mg/dL (2.5-4.5 mg/dL) and PTH on 3 consecutive tests 1.2, 1.3 and 1.2 pg/mL (15-65 pg/mL). Her 24h urine calcium was 900 mg, 25-OH-D 40 ng/mL (30-58 ng/mL) and 1,25-OH-D 99 pg/mL (80-146 for women in the third trimester). Abdominal ultrasound revealed multiple hypervascular liver lesions consistent with hemangiomas by MRI. Breast and neck ultrasound were normal, and chest CT revealed few non-significant 0.3-0.7 cm pulmonary nodules with no change after an interval of 3 months. She was treated with isotonic saline, loop diuretics and calcitonin. Despite this treatment, calcium levels remained high (14.1 mg/dL), and pamidronate was initiated. On 35th week gestation, she underwent a cesarean section complicated by hypocalcemia of the newborn. Eight weeks after delivery, her calcium levels are 9.4 mg/dL and PTH 18 mg/dL. According to the extensive workup and the post-partum normalization of PTH and calcium levels, we conclude that excessive secretion of placental PTHrP was the cause of hypercalcemia in this patient. No significant adverse effect of bisphosphonate on the mother or baby were seen at the short term follow up.
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