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ABSTRACT Objective The oral glucose tolerance test (OGTT) is used in the screening of gestational diabetes, in diagnosis of type 2 diabetes in conjunction with fasting blood glucose and glycated hemoglobin. The aim of this study was to examine the incidence and risk factors of adverse effects of OGTT in patients who underwent bariatric surgery, in addition to proposing standardization for ordering the OGTT in these patients. Subjects and methods This study assessed the incidence of adverse effects in 128 post-bariatric surgery patients who underwent the OGTT. Descriptive and logistic regression analysis were performed, the dependent variables were defined as the presence of signs (tremor, profuse sweating, tachycardia), symptoms (nausea, diarrhea, dizziness, weakness), and hypoglycemia (blood glucose ≤ 50 mg/dL). Results One hundred and seventeen participants (91.4%) were female; 38 (29.7%) participants were pregnant. High incidence (64.8%) of adverse effects was observed: nausea (38.4%), dizziness (30.5%), weakness (25.8%), diarrhea (23.4%), hypoglycemia (14.8%), tachycardia (14.1%), tremor (13.3%), profuse sweating (12.5%) and one case of severe hypoglycemia (24 mg/dL). The presence of signs was associated with hypoglycemia (OR = 8.1, CI 95% 2.6-25.1). The arterial hypertension persisted as a risk factor for the incidence of signs (OR = 3.6, CI 95% 1.2-11.3). Fasting glucose below 75 mg/dL increased the risk of hypoglycemia during the test (OR = 9.5, CI 95% 2.6-35.1). Conclusion In this study, high incidence of adverse effects during the OGTT was observed in post-bariatric surgery patients. If these results are confirmed by further studies, the indication and regulation of the OGTT procedure must be reviewed for these patients.

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ABSTRACT Objective To define the normal range of TSH in the first trimester of gestation and to evaluate the correlation between maternal TSH and obstetric and neonatal outcomes. Subjects and methods Prospective study. Women without known or clinically suspected thyroid disease and without risk factors for thyroid dysfunction, who became pregnant spontaneously and were initially evaluated up to week 12 of gestation, were included. Women with positive anti-thyroperoxidase antibodies, twin pregnancy, hyperemesis gravidarum, and trophoblastic disease were excluded. Results In the 660 pregnant women, the mean, median, and 2.5th and 97.5th percentiles of TSH were 0.9, 0.96, 0.04 and 2.68 mIU/L, respectively. TSH was undetectable in 2%, < 0.5 mIU/L in 17.4%, > 2 mIU/L in 9.7%, > 2.5 mIU/L in 4.7%, and > 3 mIU/L in 1%. None of the women received levothyroxine or antithyroid drugs during pregnancy. In addition, there was no difference in obstetric or neonatal outcomes when women with TSH ≤ 0.1, between 0.1 and 2.5, and between 2.5 and 4 mIU/L were compared. Conclusion In the population studied, the TSH value corresponding to the 97.5th percentile was 2.68 mIU/L in the first trimester of gestation.

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ABSTRACT Objective Prolactin is a multifunctional pituitary hormone. The effect of prolactin on platelet activation is not well understood. Prolactinomas are the most common type of pituitary adenomas, and they are medically responsive to dopamine agonists. Mean platelet volume (MPV) is a marker of platelet function and activation. The aim of this study was to evaluate MPV values before and 6 months of cabergoline treatment when normoprolactinemia was achieved. Subjects and methods A total of 101 newly diagnosed prolactinoma patients and 102 healthy control subjects were included in the study. Patients with hematological disorders that affect MPV and those on medications were excluded. Prolactin, platelet count and MPV levels were recorded before and 6 months after the initiation of cabergoline treatment (0.5 to 1 mg, two times a week). Results There was no significant difference in platelet count and MPV before and after 6 months of treatment with cabergoline in patients with prolactinoma compared with the control group (p > 0.05). Conclusion Our results showed that MPV, a marker of platelet function, was unchanged in patients with prolactinoma.

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ABSTRACT Objective Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. Subjects and methods Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. Results Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. Conclusions The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH.

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ABSTRACT Objective The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation. Subjects and methods Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I. Results A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation. Conclusions Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

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ABSTRACT Objectives Western dietary pattern predisposes to weight gain, insulin resistance and cardiometabolic diseases. Promoting satiety via modifications in diet composition could be useful to fight weight gain. Mediterranean diet which is recognized to be cardioprotective contains high fiber and unsaturated fat contents. We compared the effects of distinct breakfast patterns on satiety of individuals at cardiometabolic risk, and examined the correlation of satiety level after each breakfast intervention period with glucose parameters. Materials and methods In this 10-week cross-over clinical trial, 54 individuals with weight excess were submitted to 2 types of 4-week isocaloric breakfasts (2-week washout), one typically Brazilian and a modified one, differing concerning fiber and types of fatty acids contents. Clinical data were collected before and after each breakfast. A satiety scale was applied at fasting and 10, 30 and 120’ after breakfast consumption. Repeated measures ANOVA, Student t test or non-parametric correspondents were used; correlations were tested by Pearson or Spearman coefficients. Results Anthropometric variations after breakfasts were not significant. Only after the modified breakfast, reduction in blood pressure levels was observed. The satiety level did not show significant variation across each period or between the breakfasts. Non-significant correlation between satiety and glucose, insulin and HOMA-IR values after each intervention period was observed. Conclusion We conclude that different breakfast compositions do not alter satiety level, which is not correlated to glucose parameters in overweight individuals. Stronger modifications of daily meals might be necessary to differentiate satiety levels under distinct dietary patterns.

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ABSTRACT Objective Several studies have shown that left ventricular (LV) dysfunction is increased in individuals with diabetes. However, there are scarce data about LV function in prediabetics. This study assessed the early changes in LV diastolic and systolic myocardial function in normotensive prediabetics using tissue Doppler echocardiography (TDE). Subjects and methods We evaluated 94 patients with prediabetes (mean age of 50.8 ± 6.9 years, 78 female) without known cardiovascular diseases and 70 healthy volunteers with similar demographic characteristics. Systolic and diastolic function of the left ventricle was evaluated with transthoracic echocardiography according to the latest consensus recommendations including TDE. Results The mean results of septal and lateral parts of the mitral annulus Pulsed wave TDE showed that myocardial systolic wave (Sm), myocardial early diastolic wave (Em) and Em to atrial peak velocity (Am) ratio were significantly lower whereas early diastolic peak flow velocity (E) to Em ratio, myocardial isovolumetric relaxation time (IVRTm), myocardial isovolumetric contraction time (IVCTm) and myocardial performance index (MPI) values were significantly higher in patients with prediabetes (preDM). In addition, mean left atrium (LA) diameter measured with M-mode echocardiography was significantly higher in prediabetics than controls. Conclusion PreDM is associated with subclinical LV systolic and diastolic dysfunction as evaluated by TDE.

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ABSTRACT Objective The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. Subjects and methods Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. Results The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). Conclusions The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

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ABSTRACT Objective In this study, the effects of a green banana pasta diet on the oxidative damage from type 1 diabetes mellitus (DM) were investigated. Materials and methods Formulations containing 25 (F25), 50 (F50), and 75% (F75) of green banana pasta were prepared and included in a 12-week diet of Wistar rats with alloxan-induced type 1 DM. The effects of these formulations in preventing oxidative damage in kidneys and liver homogenates of rats were evaluated using the TBARS assay (lipid peroxidation in liver) and the DNPH assay (protein oxidation in liver and kidneys). Furthermore, the effects of the formulations on the fasting glycemia, fructosamine levels, renal function (creatinine), liver function (enzymes aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), and lipid profile (total cholesterol and fractions) in the serum of rats were evaluated in addition to the evaluation of the centesimal composition and microbiological analysis of the produced green banana pasta. Results An F75 diet prevented hyperglycemia in diabetic rats (p < 0.05) compared to the diabetic rats fed a standard diet (commercial feed). Notably, the protein oxidation in both the liver and kidneys were prevented in diabetic rats on the F50 or F75 diets compared to the control group, whereas the lipid peroxidation was only prevented in the liver (p < 0.05). Moreover, all formulations prevented an increase in the amount of triglycerides in the serum of the rats. The F25 and F50 diet prevented the increase of cholesterol, and the F75-based diet of ALT and fructosamine (p < 0.05) supported the anti-hyperglycemic effects and the protection against oxidative damage. Conclusion The green banana pasta (F75) diet showed great potential for preventing complications associated with diabetes.

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ABSTRACT Objective Ultrasound-guided fine-needle aspiration (US-FNA) biopsy has proven to be an accurate and efficient tool in thyroid nodule evaluation. We evaluated whether cell block adds to the diagnostic accuracy of US-FNA. Subjects and methods Three hundred twenty-eight consecutive patients underwent US-FNA, cytology and cell block evaluation. Six slides were prepared for each patient and stained by Papanicolaou and Giemsa techniques. The residual hemorrhagic aspirate in the syringe and needle was fixed in 10% formalin and paraffin-embedded (cell block). The histological sections were examined as a complementary diagnostic tool to US-FNA. Results The study population comprised 89% females and the mean age was 57.4 ± 13.7 years. The mean nodule size was 2.3 ± 1.2 cm. US-FNA cytological results were as follows: Bethesda I, 17.1% (n = 56); Bethesda II, 61.6% (n = 202); Bethesda III, 9.5% (n = 31); Bethesda IV, 5.8% (n = 19); Bethesda V, 2.4% (n = 8), and Bethesda VI, 3.6% (n = 12). Cell blocks were obtained in 100% of cases and were considered diagnostic in 89.6%. Combined cytological and cell block (cyto-cell block) results were as follows: unsatisfactory, 4.3% (n = 14); benign, 72.6% (n = 238); indeterminate, 11.3% (n = 37); follicular lesion, 5.8% (n = 19); suspicious for malignancy, 2.4% (n = 8), and malignant, 3.6% (n = 12). The sensitivity and specificity for cyto-cell block was 100% and 90%, respectively, and the accuracy was 94%. Cyto-cell block analysis reduced the rate of unsatisfactory samples (p < 0.001). Conclusions The cyto-cell block interpretation improved the efficiency of US-FNA. This simple, fast and low-cost technique should be used as an adjunctive test in thyroid nodule evaluation. Arch Endocrinol Metab. 2016;60(4):367-73

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ABSTRACT Clinically nonfunctioning pituitary adenomas (NFPA) are the most common pituitary tumors after prolactinomas. The absence of clinical symptoms of hormonal hypersecretion can contribute to the late diagnosis of the disease. Thus, the majority of patients seek medical attention for signs and symptoms resulting from mass effect, such as neuro-ophthalmologic symptoms and hypopituitarism. Other presentations include pituitary apoplexy or an incidental finding on imaging studies. Mass effect and hypopituitarism impose high morbidity and mortality. However, early diagnosis and effective treatment minimizes morbidity and mortality. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism is to provide a review of the diagnosis and treatment of patients with NFPA, emphasizing that the treatment should be performed in reference centers. This review is based on data published in the literature and the authors’ experience. Arch Endocrinol Metab. 2016;60(4):374-90

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ABSTRACT The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype.

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ABSTRACT Objective There is no information about the frequency of malignancy specifically in the case of thyroid nodules with highly suspicious sonographic features, but with two fine needle aspiration (FNA) showing benign cytology. This was the objective of the study. Subjects and methods We report the results of 105 patients with thyroid nodules considered “highly suspicious” according to the ultrasonographic classification of American Thyroid Association, in whom FNA revealed benign cytology on two occasions (interval of 6 months). Results Thyroidectomy was performed in 11 cases due to desire of the patient or significant growth of the nodule. In these patients, cytology continued to be benign in 9, was non-diagnostic in 1, and suspicious in 1. Histology revealed papillary carcinoma in only one nodule. In patients in whom a third FNA was obtained for this study (n = 94), cytology continued to be benign in 86, became non-diagnostic in 5, indeterminate in 2, and suspicious in 1. The last 8 patients (with non-benign cytology) were submitted to thyroidectomy and histology revealed malignancy in only one nodule. Conclusion The rate of malignancy found here for nodules with highly suspicious sonographic features, even after two FNA showing benign cytology, was 2%. We believe that in these cases, the continuation of follow-up consisting of ultrasound at intervals of 2 years may still be adequate.