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ABSTRACT Objective Autonomic nervous system, especially the sympathetic nervous system, may stimulate the expression of peroxisome proliferator-activated receptor γ coactivator-1α, which regulates irisin. This study aimed to explore whether there was any association between autonomic function as assessed by heart rate related indices and irisin release following acute exercise. Subjects and methods Seventeen healthy adults were asked to perform an incremental exhaustive cycling as well as an incremental exhaustive running separately on different days. Heart rate was monitored, and blood samples were collected before, immediately, 10-, and 60-minutes post-exercise. Serum irisin was measured using ELISA kit. Results Markers for autonomic function, such as heart rate at rest, peak, or recovery, heart rate reserve, heart rate recovery, and chronotropic index, were comparable between cycling and running (all P > 0.10). Irisin was increased immediately following both exercise. No significant association was observed between heart rate at rest, peak, or recovery and irisin level at the corresponding time-point, as well as between heart rate reserve, heart rate recovery, or chronotropic index and exercise induced irisin release, with or without controlling for age, body mass index, and glucose (all P > 0.10). Conclusions Autonomic function might not be associated with irisin release in healthy adults. Arch Endocrinol Metab. 2020;64(3):201-4

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ABSTRACT The Human Genome Project has significantly broadened our understanding of the molecular aspects regulating the homeostasis and the pathophysiology of different clinical conditions. Consequently, the field of nutrition has been strongly influenced by such improvements in knowledge – especially for determining how nutrients act at the molecular level in different conditions, such as obesity, type 2 diabetes, cardiovascular disease, and cancer. In this manner, characterizing how the genome influences the diet and vice-versa provides insights about the molecular mechanisms involved in chronic inflammation-related diseases. Therefore, the present review aims to discuss the potential application of Nutritional Genomics to modulate obesity-related inflammatory responses. Arch Endocrinol Metab. 2020;64(3):205-22

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ABSTRACT Prader-Willi syndrome (PWS) is a genetic disorder caused by the absence of gene expression in the 15q11.2-q13 paternal chromosome. Patients with PWS develop hypothalamic dysfunction that can lead to various endocrine changes such as: obesity, growth hormone deficiency, hypogonadism, hypothyroidism, adrenal insufficiency and low bone mineral density. In addition, individuals with PWS have increased risk of developing type 2 diabetes mellitus. This review summarizes and updates the current knowledge about the prevention, diagnosis and treatment of endocrine manifestations associated with Prader Willi syndrome, especially diagnosis of growth hormone deficiency, management and monitoring of adverse effects; diagnosis of central adrenal insufficiency and management in stressful situations; screening for central hypothyroidism; research and treatment of hypogonadism; prevention and treatment of disorders of glucose metabolism. Careful attention to the endocrine aspects of PWS contributes significantly to the health of these individuals. Arch Endocrinol Metab. 2020;64(3):223-34

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ABSTRACT Objective Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. Subjects and methods Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. Results A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. Conclusion Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42

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ABSTRACT Objective Intrathyroid injection of dexamethasone (IID) was used for decrease the relapse rate of hyperthyroidism in the treatment of Graves’ disease (GD), but the mechanism is still unclear. We aimed to explore the effect of IID on T help (Th)1/Th2 cells and their chemokine in patients with GD. Subjects and methods A total of 42 patients with GD who were euthyroidism by methimazole were randomly divided into IID group (n = 20) and control group (n = 22). Thyroid function and associated antibody, Th1/Th2 cells proportion, serum CXCL10 and CCL2 levels, and CXCR3/CCR2 mRNA expression in peripheral blood mononuclear cells before and after 3-month IID treatment were tested by chemiluminescence assay, Flow cytometry, ELISA, and real-time PCR, respectively. Thyroid follicular cells were stimulated by IFN-γ and TNF-α and treated with dexamethasone in vitro. CXCL10 and CCL2 levels in supernatant were determined. Results After 3-month therapy, the proportion of Th2 cells and serum CCL2 levels, as well as TPOAb, TRAb levels and thyroid volume decreased in IID group (p < 0.05). However, the proportion of Th1 and CXCL10 levels had no change in IID group and control (p > 0.05). The CXCR3/CCR2 ratio had no change in both groups (p > 0.05). Conclusion IID therapy could inhibit peripheral Th2 cells via decreasing CCL2 level in peripheral blood, and this result partly explain the effects of IID therapy on prevention of relapse of GD. Arch Endocrinol Metab. 2020;64(3):243-50

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ABSTRACT Objective We aimed to evaluate the impact of minimal extrathyroidal extension (mETE) alone on the risk of recurrence of papillary thyroid carcinoma (PTC). The impact of other factors, including multifocality, age, tumor size, and stimulated thyroglobulin (sTg) values was also assessed. Subjects and methods We retrospectively analyzed 1,108 PTC patients from a medical institution, who presented tumors ≤ 4 cm without any adverse characteristics other than mETE. Patients were classified according to their response to initial treatment 12 to 24 months after surgery as proposed by the 2015 American Thyroid Association (ATA) guideline. Statistical analysis was performed using multivariate logistic regression and receiver operating characteristic (ROC) curve. Results In the multivariate logistic regression analysis, mETE did not have an impact on the response to initial treatment (p = 0.44), similar to multifocality, age, and tumor size. Initial Tg value was the only variable associated with a poor response (p < 0.01, odds ratio = 1.303, 95% confidence interval 1.25-1.36). The ROC analysis revealed that Tg was significant (area under curve = 0.8750); the cutoff value of sTg as a predictor of poor response was 10 ng/mL (sensitivity = 72.2%, specificity = 98.5%). Conclusion For low-risk PTC presenting mETE as the only aggressive feature, the initial sTg value is essential to identify patients who may have a poor response after initial treatment and benefit from further treatment. Arch Endocrinol Metab. 2020;64(3):251-6

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ABSTRACT Objective To assess the utility of bioimpedance (BIA) and skinfolds thickness (SF) in body fat percentage measuring (%BF) compared to the reference method dual-energy x-ray absorptiometry (DXA) in Brazilian reproductive age women, as well as to estimate of inter- and intra-observer precision for SF. Subjects and methods 170 women aged 18-37 years with BMI between 18 and 39.9 kg/m2 were selected for this cross-sectional study. Body density was evaluated through equations proposed by Jackson, Pollock and Ward (1980) (EqJPW) and Petroski (1995) (EqPET), and %BF was estimated by BIA, DXA and Siri’s formula (1961). The SF were measured by two separate observers: A and B (to determine inter-observer variability), who measured the folds at three times with 10-minute interval between them (to determine intra-observer variability – we used only observer A). Results The %BF by DXA was higher than those measured by SF and BIA (p<0.01, for all) of 90 volunteers. The Lin coefficient of agreement was considered satisfactory for %BF values obtained by EqJPW and BIA (0.55) and moderate (0.76) for sum of SF (ΣSF) values obtained by EqJPW and EqPET. No agreement was observed for the values obtained by SF (EqJPW and EqPET), BIA and DXA. Analysis of inter- and intra-observer of 59 volunteers showed that different measures of SF thickness met acceptability standards, as well as the % BF. Conclusion BIA and SF measurements may underestimate %BF compared with DXA. In addition, BIA and SF measurements are not interchangeable with DXA. However, our results suggest the equation proposed by Jackson, Pollock and Ward (three skinfolds) compared to BIA are interchangeable to quantify the %BF in Brazilian women in reproductive age. Furthermore, our results show acceptable accuracy for intra- and inter-observer skinfold measurements. Arch Endocrinol Metab. 2020;64(3):257-68

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ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

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ABSTRACT Objective Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. Subjects and methods A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. Results Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn’t show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. Conclusions Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81

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ABSTRACT Objective Hypoparathyroidism is a rare condition, whose most common etiology is complications of neck surgery. The aim of the study was to identify the clinical and biochemical profile of the patients with diagnosis of hypoparathyroidism, including the frequency of symptoms, clinical signs, long-term complications and disease control. Additionally, the study sought to know what the medication profile was, and the doses required by the patients. Subjects and method A retrospective cohort study was conducted wherein all patients with ICD-10 codes associated with hypoparathyroidism between 2011 and 2018 at the Hospital Universitario San Vicente Fundación were included. We investigated the etiology of the disease; biochemical profile including lowest serum calcium, highest serum phosphorus, 25OHD levels, calciuria and calcium/phosphorus product; medication doses, disease control, and presence of complications, especially renal and neurologic complications were also evaluated. Results The cohort included 108 patients (99 women/9 men) with a mean age of 51.6 ± 15.6 years. The main etiology was postoperative (93.5%), the dose of elemental calcium received was relatively low (mean 1,164 mg/day), and in only 9.2% of cases more than 2,500 mg/day of elemental calcium was necessary. We were able to evaluate the follow-up in 89 patients, and found that only 57.3% met the criteria for controlled disease. Conclusion The clinical profile of patients with hypoparathyroidism in our cohort is similar to that described in other international studies, with predominantly postoperative etiology. With standard therapy, only adequate control is achieved in a little more than half of patients. Arch Endocrinol Metab. 2020;64(3):282-9

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ABSTRACT Objective To evaluate the use of metformin for preventing cesarean deliveries and large-for-gestational-age (LGA) newborn (NB) outcomes in non-diabetic obese pregnant women. Subjects and methods This is a randomized clinical trial with obese pregnant women, divided into 2 groups: metformin group and control group, with followed-up prenatal routine. The gestational age of participants was less than or equal to 20 weeks and were monitored throughout entire prenatal period. For outcomes of delivery and LGA newborns, absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated with a 95% confidence interval (CI). Results 357 pregnant women were evaluated. From the metformin group (n = 171), 68 (39.8%) subjects underwent cesarean delivery, and 117 (62.9%) subjects from the control group (n = 186) had intercurrence (p < 0.01). As for the mothers’ general characteristics, there was significance for marital status (p < 0.01). Maternal-fetal results presented reduced preeclampsia (p < 0,01). Primary prophylactic results presented an ARR of 23.1 times (95% CI: 13.0-33.4) with NNT of 4 (95% CI: 3.0-7.7) and no significant values for LGA NB (p > 0.01). Secondary prophylactic outcomes presented decreased odds ratio for preeclampsia (OR = 0.17, 95% CI: 0.10-0.41). Conclusion The use of metformin reduced cesarean section rates, resulted in a small number of patients to be treated, but it did not reduce LGA NB. Administering a lower dosage of metformin from the early stages to the end of treatment may yield significant results with fewer side effects. Arch Endocrinol Metab. 2020;64(3):290-7

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ABSTRACT Objectives The aim of this study was to evaluate the association between nutritional intake and metabolic syndrome in otherwise healthy middle-aged Korean women. Subjects and methods Retrospectively, medical records were reviewed for nutritional intake of 2,182 Korean women who had undergone routine medical check-ups from 2010 to 2016 at Pusan National University Hospital. The patients who met diagnostic criteria for metabolic syndrome based on NCEP-ATPIII were included, and each of the patients was assessed through self-report questionnaires and individual interview with a health care provider. The recommended dietary allowance (RDA) for women in Republic of Korea was based on 2015 criteria discussed in Dietary Reference Intake for Koreans, organized by the Ministry of Health and Welfare. Results Through univariate analysis, daily calorie, protein, fat, and carbohydrate consumption were significantly higher and exceeded RDA in the patients with metabolic syndrome; other than major nutrients, iron, vitamin B2, and niacin were also consumed in excess of the RDA in these patients. Multivariate analysis showed that carbohydrate consumption, along with protein and vitamin B2, were significantly higher in the patients with metabolic syndrome. Conclusion In middle-aged Korean women, high consumption of carbohydrates, along with protein and vitamin B2, was found to have a statistically significant association with the presence of metabolic syndrome. Arch Endocrinol Metab. 2020;64(3):298-305

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ABSTRACT Objective Ultrasound assessment plays an important role in the diagnosis, and monitoring of subacute thyroiditis (SAT). However, the relationship between ultrasonographic findings and severity or prognosis of the disease is not known. The aim of the present study was to evaluate the relationship between bilateral and unilateral disease involvement and severity and prognosis of the disease. Subjects and methods The initial laboratory values, ultrasonographic findings and long-term outcomes of 247 SAT patients were evaluated retrospectively. Results In the ultrasonographic evaluation, bilateral involvement was detected in 154 patients, and unilateral involvement in 93 patients at the time of diagnosis. No significant difference was found between patients with bilateral or unilateral disease at the time of diagnosis in respect of the initial acute phase reactants. FT4 was significantly higher and TSH was significantly lower in the group with bilateral disease. Bilobar or unilobar disease on ultrasound at the time of diagnosis was not found to be a risk factor for permanent hypothyroidism or recurrence. The mean thyroid volume was determined to be 22.5 ± 10 cm3 at the beginning of treatment, and 11.2 ± 8 cm3 at the end of treatment. The initial thyroid volume and the thyroid volume at the end of treatment were significantly lower in patients who developed hypothyroidism. Conclusion There was no relationship between initial acute phase reactants and bilateral or unilateral involvement of the disease. FT4 levels were found to be associated with the extension of the disease. The risk of recurrence and permanent hypothyroidism are not associated with the initial ultrasonographic aspect. Arch Endocrinol Metab. 2020;64(3):306-11

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ABSTRACT Objective To identify the level of physical activity and glycemic variability of adolescents with type 1 diabetes mellitus and to compare glycemic variability on days with different amounts of moderate to vigorous physical activity (MVPA). Subjects and methods A sample of 34 subjects aged 10 to 15 years, 18 (52.94%) female; age: 13.04 ± 1.94; HbA1c: 9.76 ± 1.51. Physical activity was measured by wGT3X accelerometer. The glucose data were obtained using continuous glucose monitoring, and the following glycemic variability measures were calculated: standard deviation (SD), low blood glucose index (LBGI), high blood glucose index (HBGI), mean amplitude of glycemic excursions (MAGE), glycemic risk assessment in diabetes equation (GRADE) and coefficient of variation (CV). The most and least active days (the days with greater and lesser time dedicated to physical activities of moderate to vigorous intensity, respectively) were identified. In addition, based on the whole period of accelerometer use, daily means of time spent in MVPA were identified among participants, who were then divided into three groups: up to 100 minutes; from 101 to 200 minutes and above 201 minutes. Then, the measures of glycemic variability were compared among the most and least active days and among the groups too. Results The amount of MVPA was significantly different between the days evaluated (237.49 ± 93.29 vs. 125.21 ± 58.10 minutes), but glycemic variability measures did not present a significant difference. Conclusion Despite the significant differences in the amount of MVPA between the two days evaluated, the glycemic variability did not change significantly. Arch Endocrinol Metab. 2020;64(3):312-8

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ABSTRACT Objective Our objective in this study was to evaluate the factors predicting female sexual dysfunction (FSD) in patients with diabetes mellitus (DM). Subjects and methods The study included 149 women with DM. Sexual function was evaluated with the Female Sexual Function Index (FSFI) questionnaire, in which total scores under 26.55 characterized the occurrence of FSD (Group 1 > 26.55, Group 2 < 26.55). We recorded the patients’ demographic, metabolic, and hormonal data. Ophthalmologic, neurologic, and renal complications were also evaluated. The antioxidant status of the patients in both groups was determined by measuring the activity of the enzymes paraoxonase-1 (PON-1) and arylesterase (ARE). Results Based on the FSFI scores, 60 patients were allocated to Group 1 (26.6 ± 12.3) and 89 to Group 2 (22.6 ± 9.5). Group 2 compared with Group 1 had significantly (p < 0.05) higher mean concentrations of glycated hemoglobin (HbA1c), glucose, triglycerides, and insulin, along with higher rates of metformin use, smoking, retinopathy, and nephropathy. The mean serum ARE concentrations were significantly lower in Group 2 compared with Group 1 (p = 0.000), but the mean serum PON-1 concentrations were similar between both groups (p = 0.218). On multivariable regression analysis, age, ARE activity, Beck Depression Inventory (BDI) score, and menopause were significant independent predictors of FSD (p < 0.05). Conclusions In this study, we evaluated the predictive factors determining FSD caused by DM. Despite the significant results found in our study, future randomized controlled studies with a long follow-up and a larger number of patients are required to determine how DM affects FSD.