ABSTRACT Objective: Considering the rarity and clinical and molecular diversity of Wolfram syndrome (WS), the objective of this study was to identify patients with a clinical presentation suggestive of WS following up at a single Brazilian diabetes service and analyze their clinical and molecular characteristics. Subjects and methods: The study included all patients with a clinical presentation of WS following up between 1991 and 2022 with early-onset diabetes mellitus and other WS signs and symptoms. A retrospective analysis was conducted, including patients’ age, sex, consanguinity, age at symptom onset, diagnosis of diabetes mellitus, optic atrophy, diabetes insipidus, neurological and psychiatric disorders, hearing loss, urinary disorders, hypogonadism, and WFS1 molecular analysis. Results: Eight patients were identified, all of whom were diagnosed with diabetes mellitus at an average age of 3.7 years. Optic atrophy, diabetes insipidus, and hearing loss were common, while psychiatric and neurological alterations were observed in some cases. Genetic analysis revealed pathogenic variants in homozygosity or compound heterozygosity. The most frequent variant was p. Val412Serfs29, present in five of the seven families. Conclusions: This study represents the second-largest Brazilian sample of WS and is the first cohort from a single center in Southeast Brazil. The patients had an early, severe, and complete clinical presentation. The genetic variants identified were consistent with previous literature descriptions. The variant p. Val412Serfs29 was particularly common in this cohort, highlighting its relevance in the region. Objective WS, , (WS) characteristics methods 199 202 earlyonset early onset symptoms conducted sex consanguinity atrophy insipidus disorders hypogonadism WFS Results 37 3 7 3. years cases heterozygosity p ValSerfs Val Serfs families Conclusions secondlargest second largest Brazil severe descriptions Val412Serfs2 region (WS 19 20 Val412Serfs 1 2

RESUMO Objetivo: Investigar a composição corporal e o perfil metabólico de indivíduos com diferentes concentrações de vitamina D sérica, da deficiência à normalidade. Métodos: Estudo transversal realizado com 106 indivíduos adultos, de ambos os sexos, divididos em três grupos de acordo com as concentrações de vitamina D: deficiência: <20ng/mL; insuficiência: 20-29,9ng/mL e suficiência: 30-100ng/mL. A avaliação antropométrica incluiu peso, altura e circunferências. Massa gorda e massa magra foram avaliadas pelo teste de bioimpedância tetrapolar. Também foram realizadas avaliação clínica e bioquímica. A resistência à insulina foi calculada pelo índice Homeostasis Model Assessment Insulin. Resultados: A análise apontou que as principais alterações dos indivíduos com deficiência de vitamina D foram valores elevados de triglicérides, lipoproteína de muito baixa densidade - colesterol, glicemia de jejum, insulina, hemoglobina glicada, índice de massa corporal, porcentagem de gordura corporal, porcentagem de massa magra, circunferência da cintura e Homeostasis Model Assessment Insulin quando comparados ao grupo Suficiência vitamina D (p<0,05). Conclusão: Observou-se que na deficiência da vitamina D ocorrem importantes alterações tanto no metabolismo como na composição corporal, essas alterações podem contribuir para o surgimento de doenças como diabetes Mellitus e síndrome metabólica.

ABSTRACT Objective: To investigate the body composition and metabolic profile in individuals in terms of different concentrations of serum vitamin D, ranging from deficiency to sufficiency. Methods: A cross-sectional study of 106 adults of both genders, who were divided into three groups according to vitamin D levels: deficiency: <20ng/mL; insufficiency: 20-29.9ng/mL; and sufficiency: 30-100ng/mL. Anthropometric evaluation included weight, height, and body circumferences. Fat mass and lean mass were assessed using the Tetrapolar bioelectrical impedance method. Clinical and biochemical evaluations were also carried out. Insulin resistance was estimated using the Homeostasis Model Assessment Insulin index. Results: The analysis showed that the main alterations in individuals in the vitamin D deficiency group were higher triglycerides, very low density lipoprotein - cholesterol, fasting blood glucose, insulin, glycated hemoglobin, body mass index, body fat percentage, lean mass percentage, waist circumference, and Homeostasis Model Assessment Insulin than those of the vitamin D sufficient group (p<0.05). Conclusion: It was found that vitamin D deficiency causes important body composition and metabolic changes, which may lead to diseases such as diabetes Mellitus and metabolic syndrome.

Objectives To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. Subjects and methods A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. Results Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. Conclusions Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients.

OBJETIVO: Este estudo teve por finalidade avaliar a perfusão miocárdica de pacientes com diabetes mellitus tipo 1 (DM1) e tipo 2 (DM2) assintomáticos, sem diagnóstico prévio de doença arterial coronariana (DAC) ou acidente vascular cerebral. MATERIAIS E MÉTODOS: Cinquenta e nove pacientes consecutivos (16 DM1, 43 DM2) foram submetidos a cintilografia de perfusão miocárdica com sestamibi-99mTc (CPM). Foram avaliados quanto ao índice de massa corpórea, controle metabólico do diabetes, dislipidemia, terapia para o diabetes, hipertensão arterial sistêmica, nefropatia, retinopatia, neuropatia periférica, tabagismo e história familiar de DAC. RESULTADOS: CPM foi anormal em 25,4%: 12 (20,3%) com alterações de perfusão e 3 com disfunção ventricular esquerda isolada. Os mais fortes preditores de perfusão miocárdica anormal foram: idade igual ou maior a 60 anos (p = 0,017, odds ratio [OR] = 6,0), neuropatia periférica (p = 0,028, OR = 6,1), nefropatia (p = 0,031, OR = 5,6) e ECG de esforço positivo para isquemia (p = 0,049, OR = 4,08). CONCLUSÃO: A isquemia miocárdica silenciosa ocorre em mais de um em cada cinco diabéticos assintomáticos. Os mais fortes preditores de isquemia foram: idade avançada, neuropatia periférica, nefropatia, retinopatia e ECG de esforço positivo para isquemia.

OBJECTIVE: This study was aimed to evaluate myocardial perfusion in asymptomatic patients with type 1 (DM1) and type 2 diabetes mellitus (DM2) without previous diagnoses of coronary artery disease (CAD) or cerebral infarction. MATERIALS AND METHODS: Fifty-nine consecutive asymptomatic patients (16 DM1, 43 DM2) underwent myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS). They were evaluated for body mass index, metabolic control of DM, type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. RESULTS: MPS was abnormal in 15 patients (25.4%): 12 (20.3%) with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0), peripheral neuropathy (p = 0.028; OR = 6.1), nephropathy (p = 0.031; OR = 5.6), and stress ECG positive for ischemia (p = 0.049; OR = 4.08). CONCLUSION: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this study were: patient age, peripheral neuropathy, nephropathy, retinopathy and a stress ECG positive for ischemia.

OBJECTIVE: The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. PATIENTS AND METHODS: We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. RESULTS: At baseline, TD prevalence was 6.82% (n = 20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95% CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. CONCLUSION: Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34% of TD was transient.

OBJETIVO: A tuberculose tiroidiana ocorre raramente. O hipotireoidismo decorrente da destruição tiroidiana é um relato raríssimo. Nosso objetivo foi descrever o caso de paciente com tuberculose tiroidiana primária e ressaltar a raridade e a importância da doença. RELATO DO CASO: Mulher, 62 anos, apresentando massa cervical extensa há quatro meses, associada à inapetência, à perda de peso, à disfonia e à disfagia. A investigação laboratorial mostrou hipotireoidismo primário. Ultrassonografia: lesão expansiva em lobo esquerdo, envolvendo musculatura subjacente. Tomografia computadorizada: massa heterogênea com centro necrótico, 13 cm de diâmetro. Biópsia por agulha fina: material serossanguinolento. Cirurgia: tireoidectomia, dissecção radical à esquerda e traqueostomia protetora. Exame anatomopatológico: processo inflamatório crônico granulomatoso com áreas de necrose caseosa e comprometimento linfonodal. Baciloscopia tiroidiana positiva. Ausência de comprometimento pulmonar. A paciente foi tratada com drogas antituberculosas. CONCLUSÕES: Tuberculose tireoidiana não é frequente, mas deve ser considerada como diagnóstico diferencial de hipotireoidismo e massa cervical anterior.

OBJECTIVE: The involvement of the thyroid by tuberculosis (TB) is rare. Hypothyroidism caused by tissue destruction is an extremely rare report. Our aim was to report a patient with primary thyroid TB emphasizing the importance of diagnosis, despite the rarity of the occurrence. CASE REPORT: Women, 62 years old, showing extensive cervical mass since four months, referring lack of appetite, weight loss, dysphagia and dysphonia. Laboratorial investigation revealed primary hypothyroidism. Cervical ultrasound: expansive lesion in left thyroid lobe, involving adjacent muscle. Computed tomography scan: 13 cm diameter cervical mass with central necrosis. Fine needle biopsy: hemorrhagic material. Surgery: total thyroidectomy, left radical neck dissection and protective tracheotomy. The pathological examination showed chronic granulomatous inflammatory process with areas of caseous necrosis and lymph node involvement. The thyroid baciloscopy was positive. Pulmonary disease was absent. The patient was treated with antituberculosis drugs. CONCLUSIONS: Thyroid TB is not frequent, and should be considered as differential diagnosis of hypothyroidism and anterior cervical mass.