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ABSTRACT Objective: To evaluate the association of neck circumference (NC) with gestational diabetes (GDM) and adverse outcomes in women with overweight and obesity. Subjects and methods: This prospective study included 132 (BMI > 25 kg/m2) pregnant women without and with GDM. Standardized questionnaire and biochemical/physical evaluation were performed during the 1st to 3rd trimester. Fifth-five women were evaluated regarding hypertension in pregnancy, type of delivery and neonatal complications (death, intensive care unit admission and hypoglycemia). Results: Women with (n = 61) and without (n = 71) GDM had similar mean (SD) pre-gestational BMI [30.3 (4.0) vs. 29.4 (3.5) kg/m2, p = 0.16]. Women with GDM were older [32 (6) vs. 28 (6) yrs, p < 0.001] and had greater NC [36.0 (2.7) vs. 34.5 (1.8) cm, p < 0.001]. NC was similar in women with GDM diagnosed in first or third trimester [p = 0.4] and was correlated with FPG [r 0.29, p = 0.01] and systolic [r 0.28, p = 0.001] and diastolic [r 0.25, p = 0.004] blood pressure. NC was associated with GDM [OR 1.25, 95%CI 1.03-1.52] adjusted for age, physical activity, education and familiar history of diabetes. In ROC analysis, the area under the curve was 0.655 and the cut-off value of 34.5 cm had 0.70 of sensitivity and 0.51 of specificity for GDM. Women who had NC ≥ 34.5 vs. < 34.5 cm had higher frequencies of hypertension [32.3 vs. 4.2%, p = 0.01]. Conclusions: In a group of pregnant women with overweight or obesity, NC can be a useful tool for identifying risk of GDM and obstetric adverse outcomes.

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ABSTRACT Objective: The prevalence of autoimmune thyroiditis (AT) in papillary thyroid carcinoma (PTC) is still controversial. The aim of this study was to investigate the frequency of coexistence of PTC with AT versus that of the coexistence of benign nodules with AT. Materials and methods: This was a cross-sectional retrospective study including patients operated on for thyroid nodules from January 2011, to April 2021. The frequency of papillary carcinomas cooccurring with AT was compared to that of benign nodules cooccurring with AT, which was assessed based on cytopathological diagnosis after thyroidectomy. Results: The study included 668 cases of benign nodules and 420 cases with PTC. No statistically significant difference was observed between cases of benign and PTC nodules regarding the presence of AT (25% vs. 28%, respectively, p = 0.177). The size of the PTC compared to that of the benign predominant nodules was significantly smaller both in the absence (0.96 ± 1.09 cm vs. 2.19 ± 1.06 cm, p < 0.05) and in the presence (0.77 ± 0.76 cm vs. 1.67 ± 1.08 cm, p < 0.01) of AT. In the binary logistic regression analysis of the PTC, the only variable associated with AT was multifocality (odds ratio: 1.750, 95% confidence intervals: 1.131-2.706, p = 0.013). The incidences of lymph node involvement and advanced stage PTC were very low both in the presence and absence of AT. Conclusion: The nodules present with PTC were not more likely to coexist with AT than benign nodules were. The small incidence of advanced PTC indicates a significant improvement in early-stage diagnosis.

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ABSTRACT Objective: There is controversy about the indication for nonalcoholic fatty liver disease (NAFLD) screening in patients with type 2 diabetes mellitus (T2D). The present study aims to contribute to NAFLD surveillance in patients with T2D, assessing the association of clinical and biological variables with hepatic stiffness and steatosis. Subjects and methods: A cross-sectional design was used, with data collection from electronic medical records, including adults with T2D who underwent transient elastography (TE) between June 2018 and December 2019. Liver stiffness and steatosis were evaluated using TE and controlled attenuation parameter (CAP), respectively, with cutoff points > 8 kpa for increased stiffness and > 275 dBm for steatosis. The relationship between clinical variables and elastography results were evaluated by bivariate correlation and multivariate analysis, using SPSS 27. Seventy-nine patients (n = 79) met the inclusion and exclusion criteria. Results: Advanced fibrosis and hepatic steatosis were detected in 17,7% and in 21,5% of the patients, respectively. There was a direct and significant correlation between CAP and BMI, waist circumference, HbA1c, triglycerides levels, and insulin doses and an inverse correlation with HDL. The waist circumference, low levels of HDL cholesterol and the insulin dose maintained a significant association with CAP values in multivariate analysis. Elastography values showed an inverse correlation with HDL and a direct correlation with BMI and insulin dose. The association was only maintained for the insulin dose in multivariate analysis. Conclusion: Our results suggest that clinical factors such as insulin dose, waist circumference, and HDL cholesterol levels could identify T2D patients more likely to present NAFLD.

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ABSTRACT Objective: This study aims to evaluate potential pancreas endocrine damage due to SARS-CoV-2 by measuring β-cell autoantibodies in COVID-19 patients. Subjects and methods: Between June and July 2020, 95 inpatients with a positive COVID-19 test result after polymerase-chain-reaction (PCR) and who met the inclusion criteria were enrolled in our study. Laboratory parameters that belong to glucose metabolism and β-cell autoantibodies, including anti-islet, anti-glutamic acid decarboxylase, and anti-insulin autoantibodies, were measured. β-cell autoantibodies levels of the patients were measured during COVID-19 diagnosis. Positive results were reevaluated in the 3rd month of control. Results: In the initial evaluation, 4 (4.2%) patients were positive for anti-islet autoantibody. Only one (1.1%) patient was positive for anti-glutamic acid decarboxylase autoantibody. No patient had positive results for anti-insulin autoantibody. FPG, HbA1c, and C-peptide levels were similar in patients who were split into groups regarding the initial positive or negative status of anti-islet and anti-GAD autoantibodies (p>0.05). In the 3rd month after the initial measurements, anti-islet autoantibody positivity of 2 (50%) of 4 patients and anti-glutamic acid decarboxylase positivity of 1 (100%) patient were persistent. Finally, 3 (3.1%) patients in the whole group were positive for anti-islet autoantibody in the 3rd month of control. No difference was determined between the initial and the 3rd month of parameters of glucose metabolism. Conclusion: Following an ongoing autoantibody positivity in the present study brings the mind that SARS-CoV-2 may be responsible for the diabetogenic effect. Clinicians should be aware of autoantibody-positive DM as a potential autoimmune complication in patients with SARS-CoV-2.

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ABSTRACT Objective: Thyroid functions in the sick newborns may be altered in the first week of life. Transient hypothyroxinemia has been reported in these babies, which could be due to the immaturity of the hypothalamic-pituitary-thyroid axis or to acute illness. We conducted this study to estimate the incidence of hypothyroxinemia and determine its risk factors in sick term newborns. Materials and methods: We analyzed free T4 (FT4) and thyroid-stimulating hormone (TSH) levels in sick term neonates (≤7 days of life) admitted to the neonatal intensive care unit. FT4 and TSH levels were estimated in the first week of life in all the enrolled neonates (N = 98) and then repeated at 14-21 days of life in 46 babies. Risk analysis was conducted using univariate and multivariate logistic regression, and numerical data was compared using the Mann-Whitney U test and t-test. Results: Hypothyroxinemia was seen in 10 (10.2%) of the admitted term babies. Male gender, vaginal delivery, presence of hypoxic ischemic encephalopathy, and need for mechanical ventilation (>24 hours) were identified as risk factors. There was a significant negative linear correlation between FT4 level in the first week of life and duration of hospital stay. Conclusion: Hypothyroxinemia is common in sick term neonates.

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ABSTRACT Introduction: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands. Subjects and methods: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC. Results: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures. Conclusion: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.

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ABSTRACT Objective: The optimal time for a neck ultrasound (US) in the follow-up of papillary thyroid cancer (PTC) after the first year is undetermined. We aimed to verify the utility of routine neck US in the surveillance of patients diagnosed with low- and intermediate-risk PTC with no evidence of disease at the one-year assessment. Materials and methods: We conducted a retrospective longitudinal study of patients with low- and intermediate-risk PTC with normal neck US, unstimulated serum thyroglobulin (Tg) < 1 ng/mL and negative anti-Tg antibodies at the one-year follow-up. Patients were divided into group 1 [undetectable Tg (<0.20 ng/mL)] and group 2 [detectable Tg but < 1 ng/mL]. The negative predictive value (NPV) of the one-year unstimulated Tg at the five-year and last follow-up visits was calculated. Results: We included n = 88 patients in group 1 and n = 8 patients in group 2. No patient from group 1 presented suspicious US findings at the five-year evaluation [NPV: 100.0% (95% confidence interval (CI): 95.5%-100.0%)], and at the last visit, only one patient had developed a lymph node classified as suspicious [NPV: 98.8% (95% CI: 93.2%-100.0%); mean follow-up: 6.7 years]. In group 2, two patients’ USs presented suspicious findings at the five-year evaluation [NPV: 75.0% (95% CI: 34.9%-96.8%)]. At the last visit, only one patient persisted with suspicious findings in the US [NPV: 87.5% (95% CI: 47.4%-99.7%); mean follow-up: 6.5 years]. Conclusion: Low- and intermediate-risk PTC with an excellent response to treatment at the one-year assessment can be safely monitored with regular unstimulated Tg assessments. Conclusions should not be drawn for Tg levels between 0.20-0.99 ng/mL.

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ABSTRACT Objective: Binge eating disorder (BED) is the most prevalent eating disorder in individuals with obesity. Its association with factors that control hunger and satiety has not yet been elucidated. We evaluated whether levels of inflammatory markers, frequency of psychiatric comorbidities, and appetite-related hormones levels differ between individuals with obesity with and without BED. Materials and methods: The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 – Clinician Version (SCID-5-CV), Binge Eating Scale, and Hospital Anxiety and Depression Scale were evaluated in 39 individuals with obesity. Plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) were measured. Results: Individuals of the BED group exhibited significantly higher percentages of altered eating patterns (hyperphagia, bingeing, post-dinner eating, feeling “stuffed”, and emotional eating), higher depressive symptom scores and levels of leptin, CRP, and TNF-α, compared to those from the non-BED group. Logistic regression showed that BED was independently associated with depressive symptoms and CRP levels. Conclusions: Individuals with obesity and BED showed greater psychiatric comorbidity, worse eating patterns and worse inflammatory profile than those without BED. BED should be assessed as an indicator of clinical severity in patients with obesity.

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ABSTRACT Objective: We assessed metrics related to inpatient glycemic control using InsulinAPP, an application available for free in Brazil, on the hospitalist-managed ward of our hospital. Subjects and methods: We performed a retrospective study of patients with type 2 diabetes (T2D) admitted from November 2018 to October 2019. InsulinAPP recommends NPH and regular insulins three times a day, in bolus-correction or basal-bolus schemes. Parameters that included BG within range of 70-180 mg/dL, insulin treatment regimen and frequency of hypoglycemia were evaluated. Results: A total of 147 T2D individuals (23% medicine and 77% surgery) were included (mean age 62.3 ± 12.7 years, HbA1c: 8.3 ± 3.0%). The initial insulin regimen was 50% bolus-correction, 47% basal-bolus and 3% with sliding scale insulin. During hospitalization, 71% patients required a bolus-basal regimen. In the first 10 days of the protocol, 71% BG measurements were between 70-180 mg/dL and 26% patients experienced one or more episodes of hypoglycemia < 70 mg/dL, and 5% with BG < 54 mg/dL. Conclusion: The results of this retrospective study indicate the InsulinAPP application using human insulin formulations was effective and safe for the management of hyperglycemia on a hospitalist-managed ward, with more than 70% BG measurements within the therapeutic range and a low rate of hypoglycemia.

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ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

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ABSTRACT Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects and methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.

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ABSTRACT Increasingly sensitive diagnostic methods, better understanding of molecular pathophysiology, and well-conducted prospective studies have changed the current approach to patients with thyroid cancer, requiring the implementation of individualized management. Most patients with papillary thyroid carcinoma (PTC) are currently considered to have a low risk of mortality and disease persistence/recurrence. Consequently, current treatment recommendations for these patients include less invasive or intensive therapies. We used the most recent evidence to prepare a position statement providing guidance for decisions regarding the management of patients with low-risk PTC (LRPTC). This document summarizes the criteria defining LRPTC (including considerations regarding changes in the TNM staging system), indications and contraindications for active surveillance, and recommendations for follow-up and surgery. Active surveillance may be an appropriate initial choice in selected patients, and the criteria to recommend this approach are detailed. A section is dedicated to the current evidence regarding lobectomy versus total thyroidectomy and the potential pitfalls of each approach, considering the challenges during long-term follow-up. Indications for radioiodine (RAI) therapy are also addressed, along with the benefits and risks associated with this treatment, patient preparation, and dosage. Finally, this statement presents the best follow-up strategies for LRPTC after lobectomy and total thyroidectomy with or without RAI.

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ABSTRACT Resistance training has shown the potential to contribute to better glycemic control in people with Type 1 Diabetes (T1D), however, there are contradictory results in this regard and a need to clarify the effects of isolated resistance training on glycemic control in T1D. The aim was to verify the effects of resistance training on the glycemic control of people with T1D. Original articles were selected, randomized and non-randomized clinical trials that aimed to verify chronic responses, through the concentrations of glycated hemoglobin (HbA1c), to a structured program of resistance exercise in the glycemia of patients with T1D. The following databases were searched; MEDLINE, PubMed, Web of Science, Scopus, ScienceDirect, LILACS, and SciELO. Five studies were included in the review. A reduction in HbA1c was observed (SMD = -0.568 ± 0.165 [95% CI = -0.891 to -0.246]; p = 0.001; I² = 82%) in patients undergoing resistance training, when compared to the control group (SMD = 1.006 ± 0.181 [95% CI = 0.653 to 1.360]; p <0.001). Two studies, with children and adolescents and longer interventions, demonstrated a significant reduction in HbA1c, increased strength, and an improved lipid profile. Resistance training was efficient for assisting in glycemic control in people with T1D and should be incorporated in treatment plans.

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ABSTRACT Central adrenal insufficiency (CAI) is a life-threatening disorder. This occurs when ACTH production is insufficient, leading to low cortisol levels. Since corticosteroids are crucial to many metabolic responses under organic stress and inflammatory conditions, CAI recognition and prompt treatment are vital. However, the diagnosis of CAI is challenging. This is not only because its clinical presentation is usually oligosymptomatic, but also because the CAI laboratory investigation presents many pitfalls. Thus, the clarification of when to use each test could be helpful in many contexts. The CAI challenge is also involved in treatment: Several formulations of synthetic steroids exist, followed by the lack of a biomarker for glucocorticoid replacement. This review aims to access all available literature to synthesize important topics about who should investigate CAI, when it should be suspected, and how CAI must be treated.

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ABSTRACT Recent studies have shown that two common methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

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SUMMARY Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and is usually idiopathic. A rare cause of reversible DCM is hypocalcemia. Calcium plays a key role in myocardial contraction. Hypocalcemia can lead to a decrease in contraction, left ventricular systolic dysfunction, and heart failure with reduced ejection fraction (EF). Hypocalcemia-related reversible DCM reports are rare. Herein, we present two cases with heart failure caused by hypocalcemia developed due to hypoparathyroidism. The first case presented with severe heart failure and an extremely low serum calcium level (4.4 mg/dL) due to idiopathic hypoparathyroidism. The second case, which was also admitted with heart failure due to hypocalcemia, had iatrogenic hypoparathyroidism due to a subtotal thyroidectomy. In both cases, patients had reduced left ventricular systolic functions (EF was 33% and 42%, respectively). After calcium replacement and heart failure treatment, calcium levels were normalized. A significant and rapid improvement in heart failure was achieved in both cases (EF 60% and 50%, respectively). Serum calcium levels should always be measured in patients with heart failure, and the etiology of hypocalcemia should be sought. In addition to the standard pharmacotherapy of heart failure with reduced EF, calcium supplementation is essential for treating these patients.