Abstract in English:ABSTRACT Dietary cholesterol is absorbed in proportion to the amount ingested, blocking its hepatic synthesis, increasing its biliary excretion, only slightly increasing production of bile acids while potentially raising the serum concentration of the atherogenic low-density lipoprotein. Humans lie midway between rats and rabbits that respond to dietary cholesterol, respectively, with high and low capacity to produce bile acids, and low or high capacity to raise blood cholesterol. There are regular studies exonerating as well as blaming dietary cholesterol as a cardiovascular risk factor, particularly in genetic hypercholesterolemic individuals. We then resorted at reviewing all meta-analyses on the subject but failed to reach at a clear conclusion useful in medical practice. Nevertheless, ingestion of the same amount of cholesterol results in wide variation in the amounts absorbed and in plasma lipoprotein profiles depending on poorly understood genetic factors. Several genetic conditions are capable of interfering with the absorption and synthesis of cholesterol. Hyperabsorption of dietary cholesterol elicits the accumulation of cholesterol in the liver and in plasma. In this regard, most cases of familial hypercholesterolemia that have a case of intestinal hyperabsorption of cholesterol also demonstrate the same defect. A practical useful suggestion is to measure for a few weeks the total serum cholesterol and its fractions at least three times before and during the intake of eggs that the candidate wishes to maintain in his usual dietary practice as an efficient procedure to identify those who respond with undesirable increases in serum cholesterol.
Abstract in English:ABSTRACT The prevalence of diabetes mellitus is increasing and is related to sedentary lifestyles and obesity. Many studies were published on the effect of lifestyle interventions on glucose regulation and delay the onset of diabetes in adults with impaired glucose tolerance (IGT) or prediabetes. This study aimed to investigate the role of lifestyle interventions in individuals with IGT or prediabetes using a meta-analytic approach. PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched from their inception up to January 2020 to select eligible randomized controlled trials (RCTs). The weighted mean difference (WMD; for fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPPG)) or relative risk (RR; for the risk of diabetes) with 95% confidence interval (CI) were calculated for pooled effect estimates using the random-effects model. Thirteen RCTs involving 3376 individuals with IGT or prediabetes were selected for this meta-analysis. The results showed that lifestyle interventions were associated with lower FPG (WMD: -0.14; 95% CI: -0.24 to -0.05 mmol/L; p=0.004) and 2hPPG (WMD: -0.66; 95% CI: -1.12 to -0.20 mmol/L; p=0.005) in adults with IGT or prediabetes. Moreover, the risk of diabetes was significantly reduced in individuals who received lifestyle interventions (RR: 0.75; 95% CI: 0.60-0.95; p=0.015). Lifestyle interventions could help improve glucose dysregulation and prevent the progression of diabetes in adults with IGT or prediabetes. Further large-scale RCTs should be conducted to assess the effects of long-term lifestyle interventions on diabetic complications in adults with IGT or prediabetes.
Abstract in English:ABSTRACT Objective: CYP21A2 mutation heterozygote carriers seem to have an increased risk of hyperandrogenism. However, the clinical relevance of the heterozygote carrier status and the reliability of hormonal testing in discriminating a carrier from a non-carrier are puzzling questions. We aimed to characterize a population of Portuguese females suspected of having non-classic congenital adrenal hyperplasia (NC-CAH) due to clinical and biochemical criteria and who have undergone CYP21A2 molecular analysis. Subjects and methods: Retrospectively, we have analyzed the clinical records of 131 females (32 girls aged 3-9 and 99 adolescents and premenopausal women aged 13-49) who underwent complete CYP21A2 molecular analysis due to suspicion of NC-CAH. We divided included participants into three groups according to the CYP21A2 molecular analysis: NC-CAH females (46), heterozygous carriers (49), and wild type (36). We then compared clinical signs and symptoms as well as biochemical and molecular data between carriers and NC-CAH individuals and between carriers and wild type females. We measured 17OHP by electrochemiluminescence immunoassay. Results: Clinical features were similar between groups. Heterozygous carriers presented higher basal and post-cosyntropin 17-hydroxyprogesterone (17OHP) than wild type individuals (p < 0.05) and lower basal and stimulated 17OHP levels than NC-CAH patients (p < 0.05). We discovered a considerable overlap between 17OHP levels among groups. The most common pathogenic variant we identified was p.Val282Leu. Conclusion: In this population of hyperandrogenic women and children, heterozygous carriers showed higher basal and stimulated 17OHP than non-carriers although normal basal and stimulated 17OHP responses do not exclude heterozygosity for CYP21A2 pathogenic variants. In this study, only the molecular analysis presented good sensitivity in identifying heterozygotes.
Abstract in English:ABSTRACT Objective: To estimate the rate of change during exercise and during recovery in moderate-continuous exercise (MCE) and high-intensity intermittent exercise (HIIE) in children and adolescents with type 1 diabetes (T1D). Subjects and methods: Participants performed 2 sessions of exercise: thirty minutes of continuous activity on a cycle ergometer (60% of VO2max) and thirty minutes (60% VO2max) interspersed with five bouts of maximum intensity lasting ten seconds every five minutes. Capillary blood glucose was measured before and after each test. The glucose rate of change in exercise (RoCE) was calculated (final blood glucose – onset blood glucose/exercise time), and the glucose rate of change in recovery (RoCR) (blood glucose 30 minutes after exercise – end of exercise blood glucose/recovery time). Results: The study included thirty-one participants (aged 13 ± 1.88 years). A lower blood glucose reduction was observed in the HIIE group, as well as better recovery values before, after, and thirty minutes after the test, respectively (333.14 ± 69.53, 226.19 ± 68.05 and 201.77 ± 66.84 versus 211.36 ± 91.03, 155.98 ± 82,68 and 165.76 ± 72.94). Covariance analyses showed a significant difference in glycemic variation between continuous and intermittent protocols immediately after exercise (−2.90 versus −2.08) and during the recovery period (−0.677 versus −0.389). Conclusions: HIIE led to a lower glucose reduction rate per minute during exercise and better recovery in the first 30 minutes after exercise compared to MCE in children and adolescents with T1D.
Abstract in English:ABSTRACT Objective: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant. Materials and methods: This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM. Results: Two hundred and forty-seven patients’ medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM ( P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others ( P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM ( P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others ( P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure. Conclusion: Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.
Abstract in English:ABSTRACT Objective: Graves’ ophthalmopathy (GO) is a vision-threatening finding observed in approximately half of Graves’ disease patients. The pathophysiology of GO is unclear, and one of the suspected factors is oxidative stress. In our study, we compared the relationship between proptosis and SH-SS in patients diagnosed with GO. Materials and methods: In this prospective study, 40 recently diagnosed Graves’ disease patients with proptosis, 40 recently diagnosed Graves’ disease patients without GO and 30 healthy individuals with similar demographic characteristics were included. Serum thiol-disulfide (SH-SS) measurements were performed. Eye examinations were performed by a single ophthalmologist to check for the presence of GO, and proptosis values were recorded with a Hertel exophthalmometer. Results: Total SH values were lower in the group with proptosis than in the other groups (p < 0.05). Total and native SH values were lower in patients without proptosis than in the control group (p < 0.05). Total SH, native SH and SS levels were independently associated with proptosis (p < 0.05). According to this analysis, it was found that increasing SS and decreasing total and native SH levels increased the probability of proptosis by 24.4%, 32.7% and 32.4%, respectively. Conclusion: A decrease in SH, which is a natural antioxidant that protects the body against oxidative stress, and an increase in SS are important signs of oxidative damage. Proptosis and SH-SS are closely related in GO. This may help us detect GO and proptosis in Graves’ patients. It can also assist in developing new options for preventing and treating GO.
Abstract in English:ABSTRACT Objectives: Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves “short long-lived people”, rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices. Material and methods: Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain). Results: Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions. Conclusions: Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.
Abstract in English:ABSTRACT Objective: The present study investigated the time needed to achieve a steady state for an accurate assessment of resting energy expenditure (REE) in adolescents with healthy weight and obesity. Materials and methods: Thirty adolescents aged 12-17 years were assigned to a group with healthy weight (GHW; n = 12, body mass index [BMI] 22.5 ± 3.6 kg/m2) and another group with obesity (GO; n = 18, BMI 34.1 ± 5.2 kg/m2). Participants underwent test-retest reliability of REE assessment as follows: a) 24 h of abstention from physical exercise, soft drinks, or caffeine; b) fasting for ~12 h; c) acclimation period of 10 min; d) 30-min assessment in a supine position. Results and discussion: A significant change occurred during the 30 min in REE. Significant differences existed between consecutive means until the 20th and 25th min for the GHW and GO, respectively. Although significant differences between trials 1 and 2 were detected during the first 5-10 min of assessment, the REE for each 5-min time point exhibited high test-retest reliability across trials in both groups (intraclass correlation coefficients range 0.79-0.99). Conclusion: The following recommendations are provided to promote accurate assessment of REE among adolescents: a) initiate the REE assessment with 10 min of acclimation to decrease restlessness; b) determine REE for a minimum of 20 min if healthy weight and 25 min if obesity; c) determine REE for a further 5 min, with the average of this last 5 min of REE data being regarded as the REE.
Abstract in English:ABSTRACT Objective: A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. Subjects and methods: We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). Results: A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Conclusion: Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.
Abstract in English:ABSTRACT Objective: There is little data about the remission phase in adolescents and young adults with newly diagnosed type 1 diabetes mellitus (T1D). The aims of this study were to determine the prevalence of remission and its predicting factors among adolescents and young adults with newly diagnosed T1D and to assess the association between remission and long-term glycemic control in this population. Subjects and methods: This is a longitudinal and retrospective study including 128 type 1 diabetic patients aged between 12 and 30 years at diabetes onset. Clinical, biological and therapeutic features were collected at diagnosis and for 5 years after diagnosis. Remission was defined by an HbA1c < 6.5% with a daily insulin dose < 0.5 IU/kg/day. Results: Twenty-three patients (18%) experienced a remission. The peak of remission prevalence was at 6 months after diabetes diagnosis. An insulin dose at discharge <0.8 IU/kg/day was independently associated with remission (p=0.03, adjusted OR [CI 95%] = 0.2 [0.1-0.9]). A low socioeconomic level was independently associated with non remission (p=0.02, adjusted OR [CI 95%] = 4.3 [1.3-14.3]). HbA1c was significantly lower during the first five years of follow-up in remitters. The daily insulin dose was significantly lower during the first four years of follow-up in remitters. Conclusions: Occurrence of remission in adolescents and young adults with newly diagnosed T1D is associated with better glycemic control and lower insulin requirements during the first 5 years of follow-up. A lower initial dose of insulin was associated with a higher percentage of remission.
Abstract in English:ABSTRACT Objectives: Evaluate the celiac disease (CD) markers, within the scope of its screening, in a pediatric population with diagnosis of type 1 diabetes (T1D) at Hospital de Braga (HB) and determine the prevalence of CD in the sample. Reflect on CD screening algorithm applied in this pediatric population. Subjects and methods: Retrospective observational study with 94 patients diagnosed with T1D at age 10 years or younger, followed up at the HB Outpatient Diabetology Consultation, including those referred from other hospitals. Record of clinical information, IgA anti-transglutaminase and anti-endomysium and HLA DQ2/DQ8 haplotypes. Results: We obtained positive serological test for CD in 4 patients. This test had 100% sensitivity and specificity. The prevalence of CD was 4.3% (n = 4). Positive HLA screening in 84.6% of patients, with both sensitivity and negative predictive value of 100% and specificity of 16.67%. Diagnosis of CD was made on average 3.40 ± 3.32 years after the diagnosis of TD1. All cases of CD registered non-gastrointestinal manifestations, none had gastrointestinal symptoms. Conclusion: This study proved that there is a higher prevalence of CD in pediatric population with TD1, when compared to general population, and clarified the importance of CD screening. Furthermore, it was observed that serological screening for CD antibodies is an excellent screening test and HLA typing, although not the most suitable first line test, can be useful in excluding the possibility of patients with T1D developing CD.
Abstract in English:ABSTRACT Objective: Cytological analysis and Bethesda classification of thyroid nodules is the standard method of diagnosing differentiated thyroid carcinoma (DTC). However, even for nodules with a non-malignant cytological diagnosis, there is a not insignificant risk of cancer. There are doubts whether this lack of certainty would influence patient prognosis. Our aim was to compare patients with DTC, classified according to the preoperative cytological diagnosis, regarding their evolution. Subjects and methods: A retrospective study was carried out with 108 DTC patients submitted to total thyroidectomy (TT) between 2009 and 2015, divided into three groups according to preoperative cytological diagnosis (Bethesda classification): classes I/II, III/IV, and V/VI. Groups were compared for evolution considering response to treatment at last evaluation as well as time disease free. Statistical analysis used ANOVA, chi squared, and Kaplan-Meier curves with p<0.05 considered significant. Results: Groups differed for time between nodule puncture and TT [in months; V/VI (2.35 ± 2.48) < III/IV (7.32 ± 6.34) < I/II (13.36 ± 8.9); p < 0.0001]. There was no significant difference between groups for evolution at final evaluation (disease free status; classes I/II: 71.4%; classes III/IV: 60%; classes V/VI: 66.6%; p = 0.7433), as well as time disease free (in months; classes I/II: 34.57 ± 25.82; classes III/IV: 38.04 ± 26.66; classes V/VI: 30.84 ± 26.34; p = 0.3841). Conclusions: DTC patients classified according to preoperative cytological diagnosis did not differ for evolution. Although patients with non-malignant cytological diagnoses were submitted to TT later, this did not affect the evolution of the cases.
Abstract in English:ABSTRACT Objective: Fibrous dysplasia (FD) is a rare bone disorder that can involve any part of the skeleton, leading to bone pain, deformities, and fractures. Treatment with intravenous bisphosphonates has been used with variable results. Therefore, we aimed to evaluate the effects of zoledronic acid (ZA) therapy in patients with monostotic or polyostotic FD. Subjects and methods: The medical records of thirteen patients with FD evaluated between 2015 and 2020 were retrospectively analyzed. In the subgroup of patients treated with ZA (n = 7), data on pain relief, changes in bone turnover markers (BTMs), and adverse events following ZA infusions were retrieved. Moreover, radiological changes in response to treatment were recorded in patients who underwent radiological follow-up. Results: Of the patients, 5 (38%) presented with monostotic whereas 8 (62%) had polyostotic FD. Bone pain was a common finding (69%), and most patients (62%) exhibited elevated baseline BTMs. Partial or complete pain relief was reported in 6 of 7 patients treated with ZA. BTMs, especially C-telopeptide of type I collagen (CTX), significantly decreased after therapy (change rate: −61.8% [IQR −71, −60%]), and median CTX levels were significantly lower than at baseline (0.296 ng/mL [0.216, 0.298] vs. 0.742 ng/mL [0.549, 0.907], respectively; P = 0.04). No radiological improvement was observed in cases with radiological follow-up (n = 3). No serious adverse effects of ZA were reported. Conclusion: ZA treatment was well tolerated and provided beneficial effects in relieving bone pain and reducing BTMs, especially CTX. Our data reinforce the role of ZA in the treatment of FD-related bone pain.
Abstract in English:ABSTRACT Objective: The primary goal of the study was to evaluate weight gain in children and adolescents with obesity during the COVID-19 pandemic period, and compare it with the period before the pandemic. Subjects and methods: The sample comprised 68 children with obesity aged between 7 and 18 years, 30 (44.1%) boys and 38 (55.9%) girls, who were attended at the pediatric endocrinology clinic of the Irmandade da Santa Casa de Misericórdia de São Paulo, SP, Brazil. Weight gain in the sample in the pre-lockdown period (December 2, 2018 to March 11, 2020) was compared with that in the lockdown period (March 11, 2020 to February 21, 2021). Results: Approximately one year before the start of the pandemic period, the mean (SD) chronological age was 10.1 years old (± 2.4), and an average weight gain of 4.4 kg (± 4.8) was observed during the pre-lockdown period described. One year after the start of the pandemic, mean (SD) chronological age was 11.8 years old (± 2.4), and an average weight gain of 8.5 kg (± 7.6) was observed in the lockdown period described. When we compared the weight gain in the two periods, it was higher in the pandemic period, both in girls and boys (p = 0.013 and 0.035, respectively). Conclusion: The results of the study show that the period of social isolation adopted to mitigate the COVID-19 pandemic was associated with increased weight gain in the studied population, probably due to a reduction in physical activities and an increase in energy consumption.
Abstract in English:ABSTRACT Objective: To evaluate the influence of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on blood glucose levels at diagnosis of gestational diabetes mellitus (GDM) and obstetric/neonatal outcomes. Subjects and methods: Retrospective cohort study including 462 women with GDM and singleton pregnancy delivered in our institution between January 2015 and June 2018 and grouped according to BMI/GWG. Results: The diagnosis of GDM was more likely to be established in the 1st trimester (T) in women with obesity than in normal-weight (55.8% vs 53.7%, p = 0.008). BMI positively and significantly correlated with fasting plasma glucose (FPG) levels in the 1stT (rs = 0.213, p = 0.001) and 2ndT (rs = 0.210, p = 0.001). Excessive GWG occurred in 44.9% women with overweight and in 40.2% with obesity (p < 0.001). From women with obesity, 65.1% required pharmacological treatment (p < 0.001). Gestational hypertension (GH) was more frequent in women with obesity (p = 0.016). During follow-up, 132 cesareans were performed, the majority in mothers with obesity (p = 0.008). Of the 17 large-for-gestational-age (LGA) birthweight delivered, respectively 6 and 9 were offsprings of women with overweight and obesity (p = 0.019). Maternal BMI had a predictive value only for macrosomia [aOR 1.177 (1.006-1.376), p = 0.041]. BMI and GWG positively correlated with birthweight (rs = 0.132, p = 0.005; rs = 0.188, p = 0.005). Conclusion: Maternal obesity is related with a major probability of diagnosis of GDM in 1stT, fasting hyperglycemia in 2ndT and a more frequent need for pharmacological therapy. Pre-gestational obesity is associated with GH, cesarean delivery and fetal macrosomia.
Abstract in English:SUMMARY A 59-year-old woman with follicular thyroid carcinoma underwent total thyroidectomy followed by radioiodine treatment. Following treatment, the whole-body scan did not show any abnormal radioiodine uptake. However, during the follow-up, the serum thyroglobulin (Tg) value increased without detectable thyroglobulin-antibodies. We performed a Ga-68 DOTA-TATE PET/CT showing a sternal lesion and several lung nodules with high somatostatin receptor density. Also, on the next day, FDG PET/CT was performed, which confirmed the findings. Considering the high levels of somatostatin receptor expression in such metastases, we planned lu177 DOTA-TATE therapy. After two cycles of lu177 DOTA-TATE injection, serum thyroglobulin significantly dropped, and she claimed that her sternal pain and dyspnea were much better. This was the case of a patient suffering from iodine-refractory follicular thyroid carcinoma, with somatostatin-receptor expression, treated with 177Lu-DOTA-TATE, showing a significant response.