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ABSTRACT Objective This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with131I. Subjects and methods The study included 53 low-risk patients (nonaggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). Results The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. Conclusions Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with 131I.

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Objective Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors.

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Objectives Evaluate the management of hypothyroidism in fertile-aged and pregnant women and compare these practices to the recommendations of the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Latin American Thyroid Society, published in 2013. Materials and methods In the first trimester of 2014, SBEM made available to all members an electronic questionnaire based on clinical scenarios in the management of gestational hypothyroidism. The responses of 406 physicians, most of them endocrinologists, were analyzed. Results Eighty-one per cent of the endocrinologists screen all their pregnant patients for thyroid dysfunction, mostly during the pregestational period or after the first prenatal visit. Following screening, 82% of the respondents initiate treatment when TSH levels are > 2.5 mIU/L while 67% monitor their pregnant patients even if TSH was normal on first trimester screening. For hypothyroid women who are planning pregnancy, 96% of the clinicians are aware of the importance of adjusting the levothyroxine (LT4) dose as soon as pregnancy is confirmed. However, opinions diverge with respect to adjusting the LT4 dose before or after reassessing thyroid function. The most widely used tests for monitoring pregnant women in use of LT4 are TSH and free T4 (62%) or TSH alone (21%). Unanimously, the treatment goal is to achieve the target TSH level for each trimester of gestation. Conclusion The recommendations of the consensus statements are incorporated into the respondents’ clinical practice. It is noteworthy that the great majority of the clinicians favor universal screening.

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ABSTRACT Objective This study aimed to determine the prevalence and the temporal trend in overweight, as well as their relationship with sociodemographic factors in adolescents from northeastern Brazil. Subjects and methods We analyzed data from two similar school-based, cross-sectional epidemiological studies conducted in 2005 (n = 2,768) and 2009 (n = 2,776), with public and private high school students of both sexes, aged 14 to 18 years, in João Pessoa, state of Paraiba, Brazil. Sociodemographic information (sex, age and economic class), body weight (kg) and height (cm) were self-reported by the students. Body mass index was classified according to International Obesity Task Force criteria. Results There was a significant increase of three percentage points in overweight prevalence from 2005 (10.1%; CI95%: 8.9-11.3) to 2009 (13.1%; CI95%: 11.4-15.5), which was of greater magnitude in males (5.0%; p < 0.001) than in females (1.8%; p = 0.085). Adjusted analysis showed that the Odds Ratio for an adolescent to show overweight in 2009 compared with 2005 was 1.34 (CI95%: 1.13-1.60), which was also greater in males (OR = 1.45; CI95%: 1.15-1.83), in adolescents aged 16 years (females – OR = 3.01; CI95%: 1.62-5.55), and in those from the middle economic class (males: OR = 1.47; CI95%: 1.03-2.23; females: OR = 1.59; CI95%: 1.01-2.53). Conclusions Prevalence of overweight in adolescents was high, and showed an increasing trend, particularly in males who belonged to the middle economic class.

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ABSTRACT Objective The objective of the present study was to investigate the effect of vitamin A supplementation on serum Th17 (IL-6, IL-17, IFNγ) and Treg (TGF-β, IL-10) related cytokines in obese and non-obese women. Subjects and methods In a randomized double blind placebo controlled design, 56 obese women were randomly assigned to receive either an oral dose of 25,000 IU retinyl palmitate or placebo per day for 4 months. Twenty eight ages matched non-obese women were also received vitamin A. At the study entry, anthropometric variables were measured and serum Th17 and Treg related cytokine profile were determined at baseline and 4 months after intervention. Results Significantly higher baseline concentrations of IL-6 were observed in obese compared with non-obese women (P < 0.05). However, the initial concentrations of other cytokines were not significantly different between groups. The mean concentrations of IL-17 and TGF-β were significantly decreased after vitamin A supplementation in non-obese and obese women respectively. Positive relationships between IL-17 and IL-10 (r = 0.42, P < 0.001), TGF-β and IL-17 (r = 0.35, P < 0.001) and between IL-10 and IFN-γ (r = 0.41, P = 0.002) in total participants were also observed. Conclusions The results of the present study showed for the first time that vitamin A supplementation reduces serum concentrations of IL-17 and TGF-β in reproductive age women. Further studies are needed to explore the possible underlying mechanisms.

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ABSTRACT Objective Our goal was to investigate which glucose measurement from the 75-g oral glucose tolerance test (OGTT) has more capability of predicting large for-gestational-age (LGA) newborns of mothers with gestational diabetes mellitus (GDM). Subjects and methods The study group consisted of 118 consecutively pregnant women with singleton pregnancy, patients of Outpatients Department of the Endocrinology, Diabetes, and Metabolic Disorders Clinic. All were prospectively screened for GDM between 24th and 28th week of pregnancy and followed to delivery. Outcome measures included: patients’ ages, pre-pregnancy BMI, BMI before delivery, FPG, 1 and 2 hour OGTT glucose values, haemoglobin A1c at third trimester, gestational week of delivery, mode of delivery and baby birth weight. Results From 118 pregnancies, 78 (66.1%) women were with GDM, and 40 (33.9%) without GDM. There were statistically significant differences (30.7 versus 5.0%, p < 0.01) between LGA newborns from GDM and control group, respectively. Gestation week of delivery and fasting glucose levels were independent predictors for LGA (Beta = 0.58 and Beta = 0.37 respectively, p < 0.01). Areas under the receiver operator characteristic curve (AUC) were compared for the prediction of LGA (0.782 (0.685-0.861) for fasting, 0.719 (0.607-0.815) for 1-hour and 0.51 (0.392-0.626) for 2-hour OGTT plasma glucose levels). Conclusion Fasting and 1-hour plasma glucose levels from OGTT may predict LGA babies in GDM pregnancies.

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ABSTRACT Objetive The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

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ABSTRACT Objective To compare the effects of the neutral protamine Hagedorn (NPH) recombinant human insulin formulations Gansulin and Humulin N® on the glycemic control of patients with type 2 diabetes mellitus (T2DM). Subjects and methods Prospective, double-blind, randomized, parallel, single-center study of 37 individuals with T2DM treated with NPH insulin formulations. The Tukey-Kramer test for multiple comparisons, the Wilcoxon paired comparison test and the Chi-Square test were used for the statistical analyses. The significance level was set at 5% (p < 0.05). Results The NPH insulin formulations Humulin and Gansulin similarly reduced the HbA1c levels observed at the end of the study compared with the values obtained at the beginning of the study. In the Humulin group, the initial HbA1c value of 7.91% was reduced to 6.56% (p < 0.001), whereas in the Gansulin group, the reduction was from 8.18% to 6.65% (p < 0.001). At the end of the study, there was no significant difference between the levels of glycated hemoglobin (p = 0.2410), fasting plasma glucose (FG; p = 0.9257) and bedtime plasma glucose (BG; p = 0.3906) between the two insulin formulations. There was no nt difference in the number of hypoglycemic events between the two insulin formulations, and no severe hyp episodes were recorded. Conclusion This study demonstrated similar glycemic control by NPH insulin Gansulin compared with human insulin Humulin N® in patients with T2DM.

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ABSTRACT Objective Vertebral fracture is the most common osteoporotic fracture, affecting quality of life and increasing mortality. Epidemiological data on incidence of vertebral fracture are scarce in Brazil and throughout Latin America. Our aim was to determine vertebral fracture incidence and risk factors in a female Brazilian population. Subjects and methods Postmenopausal women with low bone mass were studied from the Brazilian placebo group of Arzoxifene Generations Trial (n = 974), followed for up to 5 years. The primary endpoint was new vertebral fractures, detected by X-Ray. Experimental design defined two strata: A. Osteoporosis or previous vertebral fracture with osteopenia; B. Osteopenia without previous fracture. Previous fracture, T-score, ionized calcium, alkaline phosphatase, creatinine and glucose were analyzed at baseline. Crude and adjusted incidence rates of vertebral fractures were estimated and Poisson regression model was used. Results Incidence rate was 7.7 (95% CI of 5.4 to 10.9) per 1,000 person-years (PY), increasing as a function of age. Women with new vertebral fractures had higher prevalence of previous nonvertebral fracture after menopause, were older and had lower lumbar spine (LS) T-score. Fracture risk increased by 46% for each unit reduction in LS T-score. Variables correlated with new vertebral fracture were age (p = 0.034), LS T-score, stratum A (p = 0.001 for both) and previous nonvertebral fracture after menopause (p = 0.019). In the final model, LS T-score was the strongest predictor. Conclusions Incidence rate of vertebral fracture of 7.7 per 1,000 PY. Age and previous fractures were associated with new vertebral fracture, but LS T-score was the most important predictor.

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ABSTRACT Background Obesity is a well known risk factor for the development of metabolic abnormalities. However, some obese people are healthy and on the other hand some people with normal weight have adverse metabolic profile, therefore it can be assumed that there is a difference in physical characteristics amongst these people. The aim of this study was to establish whether there are somatotype differences between metabolically healthy and metabolically obese women who are obese or of normal weight. Subjects and methods Study included 230 women aged 44.76 ± 11.21y. Metabolic status was assessed according to IDF criteria, while somatotype was obtained using Heath & Carter method. Results Significant somatotype differences were observed in the group of women with normal-weight: metabolically healthy women had significantly lower endomorphy, mesomorphy and higher ectomorphy compared to metabolically obese normal-weight women (5.84-3.97-2.21 vs. 8.69-6.47-0.65). Metabolically healthy obese women had lower values of endomorphy and mesomorphy and higher values of ectomorphy compared to ‘at risk’ obese women but the differences were not statistically significant (7.59-5.76-0.63 vs. 8.51-6.58-0.5). Ectomorphy was shown as an important determinant of the favorable metabolic profile (cutoff point was 0.80). Conclusion We concluded that, in addition to fat mass, metabolic profile could be predicted by the structure of lean body mass, and in particular by body linearity.

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ABSTRACT Thyroglobulin (Tg) is the major glycoprotein produced by the thyroid gland, where it serves as a template for thyroid hormone synthesis and as an intraglandular store of iodine. Measurement of Tg levels in serum is of great practical importance in the follow-up of differentiated thyroid carcinoma (DTC), a setting in which elevated levels after total thyroidectomy are indicative of residual or recurrent disease. The most recent methods for serum Tg measurement are monoclonal antibody-based and are highly sensitive. However, major challenges remain regarding the interpretation of the results obtained with these immunometric methods, particularly in patients with endogenous antithyroglobulin antibodies or in the presence of heterophile antibodies, which may produce falsely low or high Tg values, respectively. The increased prevalence of antithyroglobulin antibodies in patients with DTC, as compared with the general population, raises the very pertinent possibility that tumor Tg may be more immunogenic. This inference makes sense, as the tumor microenvironment (tumor cells plus normal host cells) is characterized by several changes that could induce posttranslational modification of many proteins, including Tg. Attempts to understand the structure of Tg have been made for several decades, but findings have generally been incomplete due to technical hindrances to analysis of such a large protein (660 kDa). This review article will explore the complex structure of Tg and the potential role of its marked heterogeneity in our understanding of normal thyroid biology and neoplastic processes.

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ABSTRACT Objective In order to elucidate the interrelationship of adipokines in glucose hemiostasis, we determined the concentration of visfatin and adipsin in blood samples in patients with type 2 diabetes and age-matched controls after an overnight fast. Subjects and methods We enrolled 37 patients with known type 2 diabetes -21 males and 16 females, aged 62.95 ± 15.72 years and 43 controls- 28 males and 15 females, aged 60.79 ± 12.67 years. Blood samples were collected after an overnight fast and routine biochemical parameters such as glucose, cholesterol, HDL, LDL, triglycerides along with Hb1Ac, insulin and c-peptide, in addition to circulating visfatin and adipsin were determined in all samples. Data were considered significant at a level of p < 0.05. Results In patients with type 2 diabetes, circulating adipsin levels were decreased and inversely related with glucose levels while circulating visfatin was increased significantly in the fasting state. Conclusion These results implicate the adipokines adipsin and visfatin as possible participants in the pathogenesis of type 2 diabetes.

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SUMMARY The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.