Resumo em Inglês:

ABSTRACT Objective: It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Subjects and methods: Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results: Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusions: According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.

Resumo em Inglês:

ABSTRACT Objective: This study aimed to evaluate the factors affecting recurrence in subacute granulomatous thyroiditis (SAT). Materials and methods: A total of 137 patients with SAT were enrolled in the study; 98 (71.5%) were women and 39 (28.5%) were men. The patients received either steroid or nonsteroidal anti-inflammatory drug (NSAID) for eight weeks. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine (FT4), anti-thyroid peroxidase antibodies and thyroglobulin antibodies, neutrophil, lymphocyte, platelet, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio levels were evaluated. In addition, recurrence rates were compared between patients who received NSAID treatment and those who received steroid therapy. Results: Treatment modality and pretreatment TSH, FT4, and ESR were significantly different between patients with and without recurrence (p = 0.011, 0.001, 0.004, and 0.026, respectively). Compared with patients without recurrence, those with recurrence had higher pretreatment TSH levels, but lower FT4 and ESR levels. On logistic regression analysis, treatment modality was found to be an independent risk factor for recurrence. The risk of recurrence was higher in those taking steroids than in those taking NSAIDs (p = 0.015). The optimal TSH cutoff value for recurrence was 0.045 μIU/mL, with a sensitivity of 83.3% and specificity of 76% (AUC 0.794, 95% CI 0.639-0.949). Conclusions: The risk of SAT recurrence was higher with steroid therapy than with NSAIDs. Patients who had mild thyrotoxicosis had relatively high recurrence rate and may need a relatively longer duration of treatment.

Resumo em Inglês:

ABSTRACT Objectives: Diabetic nephropathy is a microvascular complication of diabetes and the most common cause of end-stage renal failure throughout the world. Videocapillaroscopy is a simple and noninvasive method that can display capillaries in the nail bed at the micron level. A few studies have been conducted on detecting retinopathy, another important diabetic microvascular complication, with videocapillaroscopy; however, no comprehensive study has been performed on diabetic nephropathy. We aimed to determine the relationship between nephropathy and capillaroscopic changes. Subjects and methods: Capillaroscopic findings of 144 patients with type 2 diabetes and 88 healthy controls were assessed prospectively by nailfold videocapillaroscopy. Twelve capillaroscopic findings were evaluated in all subjects. Results: Patients with albuminuria had more capillary aneurysms (15.5%), more microhemorrhages (15.5%), greater tortuosity (76.3%), more neoformations (29.9%), more bizarre capillaries (49.5%) and more bushy capillaries (20.6%) than the control group. In logistic regression analysis, tortuosity was significantly correlated with albuminuria (OR: 2.451, p = 0.048). Conclusions: Our findings show that the application of nailfold videocapillaroscopy can detect microvascular abnormalities in the nail bed that occur in diabetes mellitus patients compared to healthy people. Although there was no difference in the microvascular changes among the stages of diabetic nephropathy, a relationship between tortuosity and albuminuria was identified by logistic regression analysis. Nailfold videocapillaroscopy may be a new application that can be used to screen the microvascular changes that occur in diabetes mellitus.

Resumo em Inglês:

ABSTRACT Objective: Despite the treatment of anovulation, infertility is still one of the main complications in PCOS women during reproductive age, which appears to be mainly due to impaired uterine receptivity. This study investigated the transcriptome profiles of endometrium in PCOS patients and healthy fertile individuals as the control group. Material and methods: Total mRNA was extracted from endometrial tissues of PCOS patients (n = 12) and healthy fertile individuals (n = 10) during the luteal phase. After cDNA synthesis, PCR array was performed using Human Female Infertility RT² Profiler PCR Array kit (Qiagen, Cat. No: PAHS-164Z) for evaluating expression of 84 genes contributing to the female infertility. Results: PCR Array data analysis identified significantly greater expression of CSF, IL11, IL15, IL1r1, IL1b, TNF, LIF, TNFRSF10B, TGFβ, C3, ITGA4 (Cd49d), SPP1, and Calca in PCOS women than in controls (P < 0.05). However, the expression of LIFR, C2, CD55, CFD, CALCA, LAM1, LAMC2, MMP2, MMP7, MMP9, ESR, SELL, ITGB3, and VCAM1 was significantly lower in PCOS group than in controls (P < 0.05). The results revealed dysregulation of immune-inflammatory molecules, complement activation and downregulation of IGF-I as well as adhesion molecules in PCOS group. Conclusion: The findings of this study indicated some potential causes of reduced receptivity of endometrium thus compromising the fertility in PCOS patients.

Resumo em Inglês:

ABSTRACT Objectives: To evaluate the effect of sitagliptin treatment in early type 2 diabetes mellitus (T2DM) and the impact of different macronutrient compositions on hormones and substrates during meal tolerance tests (MTT). Materials and methods: Half of the drug-naive patients with T2DM were randomly assigned for treatment with 100 mg of sitagliptin, q.d., or placebo for 4 weeks and then submitted to 3 consecutive MTT intercalated every 48 h. The MTTs differed in terms of macronutrient composition, with 70% of total energy from carbohydrates, proteins, or lipids. After 4 weeks of washout, a crossover treatment design was repeated. Both patients and researchers were blinded, and a repeated-measures ANOVA was employed for statistical analysis. Results: Sitagliptin treatment reduced but did not normalize fasting and post-meal glucose values in the three MTTs, with lowered area-under-glucose-curve values varying from 7% to 15%. The sitagliptin treatment also improved the insulinogenic index (+86%) and the insulin/glucose (+25%), glucagon-like peptide-1/glucose (+46%) incremental area under the curves. Patients with early T2DM maintained the lowest glucose excursion after a protein- or lipid-rich meal without any major change in insulin, C-peptide, glucagon, or NEFA levels. Conclusion: We conclude that sitagliptin treatment is tolerable and contributes to better control of glucose homeostasis in early T2DM, irrespective of macronutrient composition. The blood glucose excursion during meal ingestion is minimal in protein- or fat-rich meals, which can be a positive ally for the management of T2DM. Clinical trial no: NCT00881543

Resumo em Inglês:

ABSTRACT Objective: The present study aimed to evaluate glucose variability and hormonal responses during and after an aerobic exercise session performed after breakfast in type 2 diabetes patients treated with metformin. Materials and methods: In this quasi-experimental study individuals underwent clinical and laboratory evaluations and maximal exercise test. After two weeks an aerobic exercise session (30 minutes at 60%-70% of the peak heart rate) was performed. At rest, during and after the exercise session, glucose variability (mean amplitude glucose excursions, glucose coefficient of variation, and glucose standard deviation) and levels of plasma glucose, insulin, glucagon, and glucagon-like-peptide-1 were evaluated. Results: Thirteen patients were enrolled in the study. Plasma glucose increased at 15 minutes during the exercise session (244.6 ± 61.9 mg/dL), and decreased at 60 min after exercise (195.6 ± 50.0 mg/dL). Glucose variability did not show any difference before and after exercise. Insulin levels at 15 min [27.1 µU/mL (14.2-42.1)] and 30 min [26.3 µU/mL (14.6-37.4)] during the exercise were higher than those at fasting [11.2 µU/mL (6.7-14.9)] but decreased 60 minutes after exercise (90 minutes) [16.6 µU/mL (8.7-31.7)]. Glucagon levels did not show any difference. GLP-1 levels increased at 30 min [7.9 pmol/L (7.1-9.2)] during exercise and decreased 60 min after exercise (90 minutes) [7.7 pmol/L (6.8-8.5)]. Conclusion: Subjects with type 2 diabetes presented expected changes in insulin, glucagon and GLP-1 levels after breakfast and a single aerobic exercise session, not accompanied by glycemic variability changes.

Resumo em Inglês:

ABSTRACT Objective: The fibroblast growth factor 23 (FGF23) has been related to biological aging, but data in elderly individuals are scant. We determined the profile of serum FGF23 levels in a population of very-old individuals and studied their correlations with parameters of bone metabolism and health markers, as functional performance. Materials and methods: This cross-sectional study was performed on 182 community dwellers aged ≥ 80 years. Serum levels of FGF23, PTH, calcium, albumin, phosphorus, creatinine, bone markers, and bone mineral density data were analyzed. Physical performance was evaluated with the stationary march (Step), Flamingo, and functional reach tests, along with questionnaires to assess falls and fractures in the previous year, energy expenditure (MET), and the Charlson index (CI). Physical activity was evaluated with the International Physical Activity Questionnaire (IPAQ). Results: Most participants (75%) had FGF23 levels between 30-120 RU/mL (range: 6.0-3,170.0 RU/mL). FGF23 levels correlated with estimated glomerular filtration rate (eGFR; r = -0.335; p = 0.001) and PTH (r = 0.318; p < 0.0001). Individuals with FGF23 in the highest tertile had more falls in the previous year (p = 0.032), worse performance in the Flamingo (p = 0.009) and Step (p < 0.001) tests, worse CI (p = 0.009) and a trend toward sedentary lifestyle (p = 0.056). On multiple regression, FGF23 tertiles remained significant, independently of eGFR, for falls in the previous year, performance in the Flamingo and stationary march tests, lean mass index, and IPAQ classification. Conclusion: In a population of very elderly individuals, FGF23 levels were inversely associated with neuromuscular and functional performances. Higher concentrations were related to more falls, lower muscle strength and aerobic capacity, and poorer balance, regardless of renal function, suggesting a potentially deleterious role of high FGF23 concentrations in musculoskeletal health.

Resumo em Inglês:

ABSTRACT Objective: To assess caregivers’ perception about the changes in the daily habits of children and adolescents with type 1 diabetes during the COVID-19 pandemic. Subjects and methods: Primary caregivers of youth aged ≤18 with or without type 1 diabetes were selected for the diabetes and the control groups. Caregivers estimated the youth's time (hours) of physical activity and screen time before and during the pandemic, and rated the quality of eating habits and medication adherence from 0 to 10. The primary outcome was the change in physical activity time, screen time, and eating habits scores during isolation. Between-group analyses and within-group comparisons were conducted. A post hoc analysis was performed using logistic regression to correct for confounding factors. Results: In total, 764 participants were included (381 diabetes group vs. 383 control group). Before the pandemic, the diabetes group presented a reduced median of physical activity (P < 0.001) and screen time (P < 0.001). During the pandemic, the difference between both groups remained similar (P = 0.58). Scores of quality of eating habits were similar in both groups before the pandemic [8.0 (7.0-9.0) vs. 8.0 (7.0-9.0), P = 0.31] but decreased during the pandemic [7.0 (5.1-8.1) vs. 8.0 (6.0-9.0), P < 0.001]. The diabetes group had a significantly worse change in eating habits scores (P < 0.01). Conclusion: During the pandemic, eating habits were significantly worse in youth with diabetes than in those without diabetes.

Resumo em Inglês:

ABSTRACT Objective: To evaluate the precipitating factors of diabetic ketoacidosis (DKA) in patients with type 1 diabetes hospitalized through the emergency department of a tertiary hospital. Materials and methods: Individuals with type 1 diabetes hospitalized for DKA from January 2005 to March 2010 (first period [P1], n = 75) and from April 2010 to January 2017 (second period [P2], n = 97) were identified through a query of electronic medical records. Data were collected by reviewing medical records. Only the first hospitalization of each participant in each period was included. Results: In P2, 44 patients (45.4%) were women, mean age was 26.2 ± 14.5 years, and 74 patients (76.3%) had a previous diagnosis of type 1 diabetes. Only 1 patient had glycated haemoglobin (HbA1c) below 64 mmol/mol (8.0%). Most patients (62.2%) had had a previous episode of DKA. In P1, non-adherence was the main cause of DKA (38.7%), followed by infection (24.0%). In P2, these rates were 34.0% and 24.7%, respectively; no statistical difference was observed between the two study periods (p = 0.790). Conclusion: Over time, non-adherence remained the main precipitating factor of DKA, followed by infection, and no significant difference was observed between the two study periods. Elevated HbA1c, outside the therapeutic range, indicates suboptimal diabetes care and may explain, at least in part, poor adherence as a precipitating factor of decompensation. Health strategies, such as improved self-management of type 1 diabetes, may contribute to a future reduction in DKA episodes.

Resumo em Inglês:

ABSTRACT Objective: Evaluating the prevalence of sarcopenia in women submitted to bariatric surgery – Roux-en-Y gastric bypass. Design: Observational, cross-sectional study. Subjects and methods: Women (18-65 years old) who underwent bariatric surgery (BG) ≥ 2 years and reached stable weight ≥ 6 months, were investigated. Control group (CG) comprised non-operated matched women with obesity. Body composition was determined through dual-energy X-ray absorptiometry. Low lean mass (LLM) was defined as appendicular lean mass index (ALM kg/height m2) < 5.5 kg/m2. Physical strength was assessed through dynamometer and sit-to-stand test (SST), whereas performance was assessed through 4-m gait speed and Short Physical Performance Battery Tests (SPPB). Sarcopenia was diagnosed in the presence of LLM and low strength. Results: One-hundred and twenty women (60 in each group, 50 ± 9.7 years old) were investigated. All anthropometric and body composition parameters were lower in BG than in CG, whereas strength and performance were similar between groups. Women with reduced strength presented high total fat mass and low physical activity level (p < 0.005). LLM was observed in 35% of BG and in 18.3% of CG (p = 0.04), whereas sarcopenia was diagnosed in 28.3% of BG and in 16.6% of CG (p = 0.12). Sarcopenic women in BG had better performance both in SST (p = 0.001) and SPPB (p = 0.004). Total lean mass (OR:1.41, 95% CI [1.18; 1.69], p < 0.001) and obesity (OR: 38.2 [2.27; 644.12], p < 0.001) were associated with sarcopenia in the multivariate analysis. Conclusion: Despite great weight loss, sarcopenia prevalence did not increase in BG and its presence was influenced by total lean mass and obesity.

Resumo em Inglês:

ABSTRACT Objective: Polycystic ovary syndrome (PCOS) begins in adolescence and has cardiovascular and metabolic components in later years. Cystatin C and high-sensitivity C-reactive protein (hs-CRP) levels and neutrophil-lymphocyte and platelet-lymphocyte ratios are associated with metabolic and inflammatory events. Here, we evaluated inflammatory and metabolic parameters in normal and overweight adolescents with PCOS. Materials and methods: This prospective case-control study enrolled 90 adolescents with PCOS and 100 matched by age and BMI healthy adolescents classified as either normal weight (NW) and overweight (OW). Groups were compared based on inflammatory and metabolic parameters (serum cystatin C, hs-CRP, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lipids, fasting blood glucose-insulin (FBG-FI), HOMA-IR levels, waist circumference [WC], and waist-hip ratio [WHR]). The relationship between the parameters were compared and predictive abilities were evaluated. Results: Cystatin C, hs-CRP, NLR, triglyceride (TG), FBG-FI, HOMA-IR, WC, and WHR were significantly higher in those with PCOS. The NW PCOS group had significantly higher TG, cystatin C, hs-CRP, and NLR versus OW controls. The highest HOMA-IR values were observed in OW PCOS (p < .05). Cystatin C and hs-CRP sensitivity and specificity were significant (p < 0.05). Cystatin C and hs-CRP were positively correlated with other metabolic parameters. Conclusion: Independent of BMI, inflammatory and metabolic parameters are significantly higher in adolescents with PCOS compared to controls and even worse in those who are also OW. Therefore, adolescents with PCOS should be encouraged to maintain healthy lifestyles and weights to avoid metabolic risks. Hs-CRP and cystatin C could be promising markers to predictive of future metabolic risks.

Resumo em Inglês:

ABSTRACT The fundamental objective of military field training exercises (FTX) is to prepare military personnel for real-life operations through simulated scenarios. These training sessions often require extreme physical efforts with prolonged, high-intensity exercises that can be combined with food restrictions and partial, or total, sleep deprivation. Such conditions can compromise an individual’s physical performance and cause tissue damage, thus affecting their health. This study aimed to perform a systematic review of the literature to identify studies that measured the changes in hormone levels and biomarkers of cellular injury and oxidative stress resulting from FTX with high levels of energy expenditure combined with food and sleep restrictions. PubMed and the Scopus database were searched for articles that combined physical effort/food restriction/sleep deprivation with military training. The initial database search identified 158 articles that were reduced to 18 after confirmation. Significant reductions were reported in thyroid hormones, T3, T4, and anabolic hormones such as testosterone, insulin and androstenedione. An exception for GH was found, which increased throughout FTX. Less distinct responses to FTX were observed with cortisol, TSH and LH. The presence of biomarkers for cellular damage (myoglobin, TNF, and CRP) and increased immune response activities were also described. The scarcity of information on oxidative stress, analyses of cellular injury and biomarkers of inflammatory responses warrants the future study of these topics, which could be helpful in facilitating the safe and effective physical preparations of the members of the armed forces.

Resumo em Inglês:

ABSTRACT The incidence of differentiated thyroid carcinoma (DTC) has increased in recent decades with early stage, low risk papillary thyroid cancer (PTC) being detected and diagnosed. As a result, the psychological, financial, and clinical ramifications of overdiagnosis and excessively aggressive therapy are being increasingly recognized with many authorities calling for a re-evaluation of the traditional “one size fits all” management approaches. To address these critical issues, most thyroid cancer guidelines endorse a more risk adapted management strategy where the intensity of therapy and follow up is matched to the anticipated risk of recurrence and death from DTC for each patient. This “less is more” strategy provides for a minimalistic management approach for properly selected patients with low-risk DTC. This has re-kindled the long-standing debate regarding the routine use of radioactive iodine therapy (RIT) in DTC. Although recent guidelines have moved toward a more selective use of RIT, particular in patients with low-intermediate risk DTC, the proper selection of patients, the expected benefit, and the potential risks continue to be a source of ongoing controversy and debate. In this manuscript, we will review the wide range of clinical, imaging, medical team, and patient factors that must be considered when evaluating individual patients for RIT. Through a review of the current literature evaluating the potential benefits and risks of RIT, we will present a risk adapted approach to proper patient selection for RIT which emphasizes peri-operative risk stratification as the primary tool that clinicians should use to guide initial RIT management recommendations.

Resumo em Inglês:

ABSTRACT Epigenetic modifications might be associated with serum triglycerides (TG) levels. This study aims to systematically review the studies on the relationship between the methylation of specific cytosine-phosphate-guanine (CpG) sites and serum TG levels. This systematic review and meta-analysis study was conducted according to the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A systematic literature search was conducted in Medline database (PubMed), Scopus, and Cochrane library up to end of 2020. All observational studies (cross-sectional, case-control, and cohort) were included. Studies that assessed the effect of DNA methylation of different CpG sites of ABCG1, CPT1A, and SREBF1 genes on serum TG levels were selected. The National Institutes of Health (NIH) checklist was used to assess the quality of included articles. Among 2790 articles, ten studies were included in the quantitative analysis and fourteen studies were included in the systematic review. DNA methylation of ABCG1 gene had significant positive association with TG levels (β = 0.05, 95% CI = 0.04, 0.05, P heterogeneity < 0.001). There was significant inverse association between DNA methylation of CPT1A gene and serum TG levels (β = −0.03, 95% CI = −0.03, −0.02, P heterogeneity < 0.001). DNA methylation of SREBF1 gene was positively and significantly associated with serum TG levels (β = 0.03; 95% CI = 0.02-0.04, P heterogeneity < 0.001). DNA methylation of ABCG1 and SREBF1 genes has positive association with serum TG level, whereas this association is opposite for CPT1A gene. The role of epigenetic factors should be considered in some populations with high prevalence of hypertriglyceridemia.

Resumo em Inglês:

SUMMARY Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes mellitus with distinct clinical features. Clinical dermatological phenotypes in MODY patients are very rare in literature. This report describes a patient with HNF1A-MODY presenting with necrobiosis lipoidica (NL) and granuloma annulare (GA). A 39-year-old asymptomatic woman, with atypical diabetes diagnosed at age 17, has a confirmed HNF1A mutation on exon 2 (c.392G>A, p.R131Q), classified as Pathogenic by the ACMG guidelines. She has reasonable metabolic control using oral anti-diabetic medications and has no chronic diabetic complications. Clinical and histologic diagnoses of both NL and GA were made. We discuss these conditions and their association with MODY.

Resumo em Inglês:

SUMMARY Thyroid angiosarcoma is an extremely rare malignancy, which occurs more frequently in the alpine region, likely associated with iodine deficiency and endemic goiter. This is an aggressive neoplasm that usually harbors a poor prognosis. We report the case of a 49-year-old Portuguese female patient presenting with a large nodule in the anterior neck region, with rapid growth and associated dysphonia. The neck ultrasound showed a hypoechogenic and heterogeneous thyroid nodule, with a larger axis of 44 mm. The fine needle aspiration cytology was not conclusive, and a biopsy of the lesion was performed. The result was suggestive of a mesenchymal tumor constituted by spindle cells and vascular clefts, showing positivity for endothelial markers and negativity for thyroglobulin, calcitonin and TTF1. The chest CT scan performed before surgery showed multiple pulmonary nodules suggestive of secondary lesions. The patient was submitted to total thyroidectomy and lymph node dissection in order to relieve compressive symptoms. A diagnosis of thyroid angiosarcoma was made after histologic examination of the surgical specimen. Despite undergoing multiple lines of palliative chemotherapy, the pulmonary lesions increased in size and number. The patient died due to respiratory failure 29 months after the diagnosis. Thyroid angiosarcoma is a rare malignancy, generally with poor prognosis. In our case, the patient presented with pulmonary metastases at diagnosis, which is a negative prognostic factor. Due to its rarity, data regarding management and treatment of this disease are scarce.

Resumo em Inglês:

SUMMARY Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring mainly in the first 6 months of life. Approximately 30% of transient NDM (TNDM) cases will have an activating mutation in the KATP channel genes ABCC8 and KCNJ11. The majority of the patients with KCNJ11 mutations who are receiving insulin treatment can be transferred to treatment with sulfonylurea (SU), with an improvement in metabolic control and quality of life. Intermittent continuous glucose monitoring (iCGM) is used to assess the current and retrospective interstitial glucose, providing information such as hypo/hyperglycemia tendency and time on target. This case report describes the use of iCGM in the transition from insulin treatment to glibenclamide in a patient with TNDM caused by a pathogenic variant of KCNJ11. This is the first report of a successful outpatient transition from insulin to glibenclamide, in a Brazilian child with TNDM using iCGM (FreeStyle Libre@). The remote monitoring and online management allowed the patient to safely stay at home during the transition from insulin to SU, especially important in the context of the COVID-19 pandemic. We conclude that iCGM is a helpful tool in cases of NDM and should be used to increase safety and speed up dose adjustments in outpatient transition from insulin to glibenclamide.