The impact of COVID-19 in children and adolescents with obesity in Brazil

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.

A Multifocal Pediatric Papillary Thyroid Carcinoma (PTC) Harboring the AGK-BRAF and RET/PTC3 Fusion in a Mutually Exclusive Pattern Reveals Distinct Levels of Genomic Instability and Nuclear Organization.

The spectrum and incidence of gene fusions in papillary thyroid carcinoma (PTC) can differ significantly depending on the age of onset, histological subtype or radiation exposure history. In sporadic pediatric PTC, RET/PTC1-3 and AGK-BRAF fusions are common genetic alterations. The role of RET/PTC as a prognostic marker in pediatric PTC is still under investigation. We recently showed that AGK-BRAF fusion is prevalent in young patients (mean 10 years) and associated with specific and aggressive pathological features such as multifocality and lung metastasis. In this pilot study, we report a unique patient harboring three different foci: the first was positive for AGK-BRAF fusion, the second was positive for just RET/PTC3 fusion and the third was negative for both rearrangements. To investigate whether AGK-BRAF and RET/PTC3 are associated with genomic instability and chromatin modifications, we performed quantitative fluorescence in situ hybridization (Q-FISH) of telomere repeats followed by 3D imaging analysis and 3D super-resolution Structured Illumination Microscopy (3D-SIM) to analyze the DNA structure from the foci. We demonstrated in this preliminary study that AGK-BRAF is likely associated with higher levels of telomere-related genomic instability and chromatin remodeling in comparison with RET/PTC3 foci. Our results suggest a progressive disruption in chromatin structure in AGK-BRAF-positive cells, which might explain a more aggressive disease outcome in patients harboring this rearrangement.

Elastography for the evaluation of thyroid nodules in pediatric patients.

OBJECTIVE: To evaluate the usefulness of elastography (using manual compression) as an additional diagnostic tool for children and adolescents with thyroid nodules. MATERIALS AND METHODS: This was a prospective study conducted between September 2012 and August 2013 at a hospital in Brazil. We performed elastography, ultrasound, and fine-needle aspiration biopsy in 32 patients between 6 and 18 years of age who had, in total, 38 thyroid nodules. RESULTS: The elastography findings correlated with the histopathological diagnosis in 78.5% of cases. In three patients, an unnecessary thyroidectomy could have been avoided if the elastography results had been prioritized. Only one malignant thyroid nodule was found to show high elasticity. CONCLUSION: Our results suggest that high elasticity of a nodule on elastography is associated with a low risk of thyroid cancer. If further confirmed in other studies, elastography may prove useful as a complementary test for screening thyroid nodules in children.

OBJETIVO: Avaliar a utilidade da elastografia (usando compressão manual) como uma ferramenta adicional de diagnóstico em crianças e adolescentes com nódulos da tireoide. MATERIAIS E MÉTODOS: Este foi um estudo prospectivo realizado entre setembro de 2012 e agosto de 2013 em um hospital no Brasil. Realizamos elastografia, ultrassonografia e biópsia por aspiração com agulha fina em 32 pacientes com idade entre 6 e 18 anos que tinham, no total, 38 nódulos tireoidianos. RESULTADOS: Os achados da elastografia em relação ao histopatológico foram corretos em 78,5% dos casos. A elastografia poderia ter evitado a tireoidectomia desnecessária de três pacientes. Apenas um nódulo maligno da tireoide foi classificado como E1. CONCLUSÃO: Nossos resultados sugeriram que a alta elasticidade de um nódulo na elastografia está associada a um baixo risco de câncer de tireoide. Caso se confirme em outros estudos, a elastografia pode ser útil como teste de triagem complementar de nódulos tireoidianos em crianças.

Elastography for the evaluation of thyroid nodules in pediatric patients / A elastografia na avaliação de nódulos tireoidianos em pacientes pediátricos

Abstract Objective: To evaluate the usefulness of elastography (using manual compression) as an additional diagnostic tool for children and adolescents with thyroid nodules. Materials and Methods: This was a prospective study conducted between September 2012 and August 2013 at a hospital in Brazil. We performed elastography, ultrasound, and fine-needle aspiration biopsy in 32 patients between 6 and 18 years of age who had, in total, 38 thyroid nodules. Results: The elastography findings correlated with the histopathological diagnosis in 78.5% of cases. In three patients, an unnecessary thyroidectomy could have been avoided if the elastography results had been prioritized. Only one malignant thyroid nodule was found to show high elasticity. Conclusion: Our results suggest that high elasticity of a nodule on elastography is associated with a low risk of thyroid cancer. If further confirmed in other studies, elastography may prove useful as a complementary test for screening thyroid nodules in children.

Resumo Objetivo: Avaliar a utilidade da elastografia (usando compressão manual) como uma ferramenta adicional de diagnóstico em crianças e adolescentes com nódulos da tireoide. Materiais e Métodos: Este foi um estudo prospectivo realizado entre setembro de 2012 e agosto de 2013 em um hospital no Brasil. Realizamos elastografia, ultrassonografia e biópsia por aspiração com agulha fina em 32 pacientes com idade entre 6 e 18 anos que tinham, no total, 38 nódulos tireoidianos. Resultados: Os achados da elastografia em relação ao histopatológico foram corretos em 78,5% dos casos. A elastografia poderia ter evitado a tireoidectomia desnecessária de três pacientes. Apenas um nódulo maligno da tireoide foi classificado como E1. Conclusão: Nossos resultados sugeriram que a alta elasticidade de um nódulo na elastografia está associada a um baixo risco de câncer de tireoide. Caso se confirme em outros estudos, a elastografia pode ser útil como teste de triagem complementar de nódulos tireoidianos em crianças.

AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma.

BACKGROUND: The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen-activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation-exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. PROCEDURE: In this study, we investigated the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK-BRAF fusion was investigated by RT-PCR and confirmed by FISH break-apart. The BRAF V600E mutation was screened using Sanger sequencing. RESULTS: AGK-BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. CONCLUSION: Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.

Fusion Oncogenes Are the Main Genetic Events Found in Sporadic Papillary Thyroid Carcinomas from Children.

BACKGROUND: Previous studies reported significant differences in the clinical presentation and outcomes of papillary thyroid carcinoma (PTC) in pediatric patients compared with adults. Previous studies have suggested that the clinicopathological differences observed between pediatric and adult PTCs may be due the existence of distinct genetic alterations. However, the knowledge of genetic events in pediatric PTCs is based primarily on studies in radiation-exposed PTCs or in the few studies that enrolled predominantly adolescent patients. The aim of this study was to characterize the known oncogenic alterations of the MAPK pathway found in adult and radiation-exposed PTCs in a cohort of predominantly sporadic pediatric PTC patients. METHODS: Thirty-five pediatric PTCs were screened for the most prevalent fusions (RET/PTC1, RET/PTC2, RET/PTC3, ETV6-NTRK3, and AGK-BRAF) and point mutations (BRAFV600E and NRASQ61) described in sporadic pediatric PTCs. The mutational status was correlated with clinicopathological data. RESULTS: Mutations were found in 20 out of 35 (57%) PTC cases. Fusion oncogenes were the main genetic alterations found. RET/PTC1-3 rearrangements were found in 13 (37%), ETV6-NTRK3 in 3 (9%), AGK-BRAF in 4 (11%), and BRAFV600E in 3 (9%). No mutation was found in NRASQ61. BRAFV600E was associated with older age and larger tumor size (p < 0.05), and RET/PTC3 was associated with a larger tumor size and multifocality (p < 0.05). CONCLUSIONS: The genetic signature in this cohort was remarkably different than that observed in adults. Although observed at a lower prevalence, the spectrum of mutations was quite similar to that described in radiation-exposed pediatric PTCs. As mutations were unidentifiable in over 40% of the PTC cases, more comprehensive studies conducted in these patients will help to decipher the genetic landscape of sporadic pediatric PTCs.

AGK-BRAF gene fusion is a recurrent event in sporadic pediatric thyroid carcinoma.

Thyroid cancer is the fastest increasing cancer worldwide in all age groups. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in both adults and children. PTC genomic landscape has been extensively studied in adults, but information regarding sporadic pediatric patients is lacking. Although BRAF V600E mutation is highly prevalent in adults, this mutation is uncommon in pediatric cases. As adult and pediatric PTC is a mitogen-activated protein kinase-driven cancer, this altered pathway might be activated by different genetic events. The aim of this study was to investigate the occurrence of AGK-BRAF fusion gene, recently described in radiation-exposed pediatric PTC, in a cohort of exclusively sporadic pediatric PTC. The series consisted of 30 pediatric PTC younger than 18 years of age at the time of diagnosis and 15 matched lymph node metastases (LNM). Primary tumors and matched LNM were screened for the presence of the AGK-BRAF fusion transcript by RT-PCR. To confirm the identity of the amplified products, randomly selected samples positive for the presence of the fusion transcripts were sequenced. Moreover, BRAF dual-color, break-apart probes confirmed BRAF rearrangement. Overall, the AGK-BRAF fusion gene was detected in 10% (3/30) of primary tumors. For one of these cases, paired LNM was also available, which also shows the presence of AGK-BRAF fusion gene. This study described, for the first time, the presence of AGK-BRAF in sporadic pediatric PTC. Understanding the molecular events underlying pediatric PTC may improve preoperative diagnosis, allow molecular prognostication and define a therapeutic approach toward sporadic PTC patients.

Thyroid-Specific Genes Expression Uncovered Age-Related Differences in Pediatric Thyroid Carcinomas.

Despite a more advanced stage of disease at presentation, a better response to radioiodine (RAI) therapy and a reduced overall mortality have been reported in pediatric differentiated thyroid cancer (DTC) in comparison to adult DTC. Few studies suggested that the better response to RAI therapy in pediatric patients might be associated with an increased expression of NIS. However, a marked heterogeneity within the pediatric group has been recognized. Children (<10 years old) usually present a more aggressive disease than adolescents (≥10-18 years old). By analyzing the expression of thyroid-specific genes in 38 sporadic pediatric tumors, we show that the expression of NIS, PDS, and TSHR was lower in children than adolescents (P < 0.05). A linear regression confirmed the association between NIS expression and age. Most significantly, NIS was expressed at similar levels in DTC from children and adults, whereas PDS and TSHR expression was even lower in DTC from children, compared to adolescents and adults. Our data suggest that biological behaviors of DTC in adolescents might differ from those in children and adults. Therefore, the premise that the expression of thyroid-specific genes is higher in tumors from pediatric patients than in adults is not entirely true and might be too oversimplified.

Predictive Potential of Twenty-Two Biochemical Biomarkers for Coronary Artery Disease in Type 2 Diabetes Mellitus.

We investigated the potential of a panel of 22 biomarkers to predict the presence of coronary artery disease (CAD) in type 2 diabetes mellitus (DM2) patients. The study enrolled 96 DM2 patients with (n = 75) and without (n = 21) evidence of CAD. We assessed a biochemical profile that included 22 biomarkers: total cholesterol, LDL, HDL, LDL/HDL, triglycerides, glucose, glycated hemoglobin, fructosamine, homocysteine, cysteine, methionine, reduced glutathione, oxidized glutathione, reduced glutathione/oxidized glutathione, L-arginine, asymmetric dimethyl-L-arginine, symmetric dimethyl-L-arginine, asymmetric dimethyl-L-arginine/L-arginine, nitrate plus nitrite, S-nitrosothiols, nitrotyrosine, and n-acetyl-ß-glucosaminidase. Prediction models were built using logistic regression models. We found that eight biomarkers (methionine, nitratate plus nitrite, n-acetyl-ß-glucosaminidase, BMI, LDL, HDL, reduced glutathione, and L-arginine/asymmetric dimethyl-L-arginine) along with gender and BMI were significantly associated with the odds of CAD in DM2. These preliminary findings support the notion that emerging biochemical markers might be used for CAD prediction in patients with DM2. Our findings warrant further investigation with large, well-designed studies.

Dyslipidemia in young patients with type 1 diabetes mellitus

Objective The association between type 1 diabetes mellitus (T1D) and dyslipidemia (DLP) increases the risk of cardiovascular disease (CVD). The aim of this study was to evaluate the presence of dyslipidemia in young T1D patients.Materials and methods The study design was cross-sectional and descriptive. We reviewed medical records of T1D patients followed at an endocrinology service, from 1998-2012. Data collected: gender, actual age and age at diagnosis, duration of T1D since diagnosis, body mass index (BMI), pubertal stage, glycemic control (GC) determined by glycated hemoglobin (HbA1c), total cholesterol (TC), HDL, LDL, triglycerides (TG). To analyze lipid profile and metabolic control, we used the Brazilian Society of Diabetes Guidelines.Results Were included 239 T1D patients, 136 (56.9%) females; mean ± SD: actual age 15.7 ± 5.0 years and at T1D diagnosis 7.3 ± 3.9; T1D duration 10.6 ± 6.4 years, 86.6% puberty, 15.1% overweight. The prevalence of DLP was 72.5%, 63.3% females, 86.6% puberty, mean ± SD: actual age 15.4 ± 4.8 years and at T1D diagnosis 7.2 ± 4.1 years, duration of T1D 10.7 ± 6.1 years. We found high-CT in 56.7%, low-HDL = 21.7%, high LDL = 44.0%, high-TG = 11.8%. Between females with DLP, 83.5% was in puberty. We find correlation between the presence of DLP, a poor GC and BMC.Conclusion We found a high prevalence of DLP in young patients with T1D, particularly in puberty females. Programs targeting the prevention of dyslipidemia should be adopted, especially for this group, in order to prevent/delay chronic complications and cardiovascular disease. Arch Endocrinol Metab. 2015;59(3):215-9.

Impact of nutritional iodine optimization on rates of thyroid hypoechogenicity and autoimmune thyroiditis: a cross-sectional, comparative study.

BACKGROUND: Since several countries have established mandatory food iodine fortification, there has been a decrease in rates of iodine deficiency disorders in parallel with an increase in prevalence of autoimmune thyroid diseases. This study compared the nutritional iodine status and the prevalence of autoimmune thyroiditis and thyroid hypoechogenicity on ultrasound in schoolchildren in São Paulo (Brazil) in two distinct periods of time in which fortified salt had different concentrations of iodine. METHODS: We conducted a cross-sectional study evaluating 206 children aged 7-14 years and without a history of thyroid disease. Assessments included measurements of thyrotropin (TSH), free thyroxine, antithyroperoxidase (anti-TPO), and antithyroglobulin (anti-TG) antibodies, urinary iodine concentration, and thyroid ultrasound. RESULTS: Mean urinary iodine concentration was 165.1 µg/L. Eleven children (5.3%) were diagnosed with autoimmune thyroiditis based on at least two of four criteria adopted in our study: positive anti-TPO or anti-TG antibody, hypoechogenicity of the thyroid parenchyma on ultrasound, and a TSH >4.0 µU/mL. Comparing our results with those from a similar study conducted during a period in which concentrations of iodine in the salt were higher (median urinary iodine concentration >300 µg/L), we observed a trend toward a lower prevalence of autoimmune thyroiditis, although no definitive conclusion could be established. CONCLUSION: The current nutritional iodine status in our cohort was within optimal levels and lower than levels found in 2003. The prevalence of autoimmune thyroiditis seems to be decreasing in parallel with a decrease in iodine intake, although we could not reach a definitive conclusion.

Comparison of methods for the measurement of body composition in overweight and obese Brazilian children and adolescents before and after a lifestyle modification program.

AIM: To compare the body composition of overweight children and adolescents by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) before and after physical activity program. METHODS: One hundred and eleven patients with mean age (SD) of 12 (1.9) participated in the study. We assessed the weight, height, waist circumference (WC), and body composition by DXA and BIA. Patients underwent a program of diet and physical activity (1 h 30 min/day, 3 times a week for 3 months) and were evaluated before and after this period. RESULTS: Mean initial zBMI were 2.3 (0.5) and waist SDS 5.9 (1.8). Significant differences were observed when we compared the measurements taken by DXA and BIA, respectively: total body fat percentage (40 and 31.5) and fat-free mass (43.1 and 50.6 kg). Regarding the trunk fat by DXA, there was a positive correlation with the WC/height ratio (r = 0.65; p < 0.01). After the intervention period, we observed a reduction in the zBMI, waist SDS, and total body fat and increase of fat-free mass by DXA. BIA only detected reduction in fat. CONCLUSION: BIA underestimates the percentage of fat and overestimates fat-free mass in relation to DXA. There is positive correlation between trunk fat and the ratio WC/height. In addition, DXA detected changes in body composition induced by a short period of physical training, unlike BIA.

Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia.

BACKGROUND: Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far. METHODS: We analyzed Melanocortin 2 receptor (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1) expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas from two untreated simple virilizing CAH cases and in two sporadic adrenal myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat numbers in AR exon 1 gene were evaluated in the 4 cases. RESULTS: The MC2R gene was overexpressed in myelolipomas from 3 out of 4 patients. AR overexpression was detected in 2 tumors: a giant bilateral myelolipoma in a CAH patient and a sporadic case. Simultaneous overexpression of AR and MC2R genes was found in two of the cases. Interestingly, the bilateral giant myelolipoma associated with CAH that had high androgen and ACTH levels but lacked MC2R and AR overexpression presented a significantly shorter AR allele compared with other tumors. In addition, X-chromosome inactivation pattern analysis showed a polyclonal origin in all tumors, suggesting a stimulatory effect as the trigger for tumor development. CONCLUSION: These findings are the first evidence for MC2R or AR overexpression in giant bilateral myelolipomas from poor-compliance CAH patients.

Importance of screening with oral glucose tolerance test for early diagnosis of cystic fibrosis-related diabetes mellitus.

OBJECTIVES: To evaluate (a) the prevalence of cystic fibrosis-related diabetes mellitus (CFRD) in a non-Caucasian population treated in a University Hospital in São Paulo, Brazil; and (b) if annual screening of patients with cystic fibrosis (CF) ≥ 10 yr of age, with oral glucose tolerance test (OGTT), resulted in early detection of CFRD. SUBJECTS AND METHODS: A cross-sectional study was performed with retrospective/prospective analysis of CF patients ≥10 yr of age. Various parameters were analyzed. Patients previously diagnosed with CFRD had their parameters collected at the time of diabetes diagnosis; others were submitted to annual OGTTs, with the parameters collected at the time of their last OGTT. RESULTS: A total of 60 subjects [29 females/31 males; mean age 19.1 yr (±7.6)] were analyzed. In our group of CF patients, we found that 30% had CFRD, 26.7% had altered response to OGTT, and 43.3% had normal glucose tolerance. Analysis of those patients with CFRD showed that the mean age at the time of diagnosis of CFRD, in patients diagnosed by OGTT screening, was 13.5 yr (±2.9) vs. 22.3 yr (±5.4) among those previously diagnosed by clinical suspicion (p < 0.001). CONCLUSIONS: The prevalence of CFRD in our patients is high, similar to the data from Caucasian populations, and significantly higher than previously reported in Brazil. Screening with OGTT resulted in earlier diagnosis of CFRD by 8 yr. These data may help convince national CF centers that CFRD is frequent, and that screening should be mandatory.

Mild adrenal insufficiency due to a NROB1 (DAX1) gene mutation in a boy presenting an association of hypogonadotropic hypogonadism, reduced final height and attention deficit disorder / Insuficiência adrenal leve causada por mutação do gene NR0B1 (DAX1) em menino com uma associação de hipogonadismo hipogonadotrófico, baixa estatura final e transtorno de déficit de atenção

Mutation on NROB1 (DAX1) gene can cause different phenotypes of adrenal insufficiency in infancy. Long-term evolution of these patients shows that it is possible to have an association with hypogonadotropic hypogonadism. In this article we describe the evolution of a patient with NROB1 gene mutation, diagnosed with a mild form of adrenal insufficiency, and we highlight the presence of hypogonadotropic hypogonadism and short stature, besides the presence of attention deficit disorder. Such associations should make physicians aware during the follow-up of patients with this disease.

Mutações no gene NROB1 (DAX1) podem levar a quadros de insuficiência adrenal com diferentes formas de apresentação na infância. A evolução a longo prazo desses pacientes mostra que pode haver associação com hipogonadismo hipogonadotrófico. Neste artigo, relatamos a evolução de um paciente com uma mutação do gene NROB1, diagnosticado com uma forma leve de insuficiência adrenal, na qual chamamos a atenção para a evolução com hipogonadismo hipogonadotrófico e baixa estatura final, além de apresentar transtorno de déficit de atenção. Tais associações devem ser motivo de atenção para os médicos no seguimento de pacientes portadores dessa alteração.

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD) / Atualização no diagnóstico e acompanhamento do diabetes melito relacionado à fibrose cística (DRFC)

Cystic fibrosis (CF) is the most common recessive autosomal disease among Caucasian. Children with CF have benefitted from advances in medical and nutritional treatments, and this can be gleaned from the improvement in the survival of these patients. The increase in the survival rate brought with it the appearance of co-morbidities related to CF. Nowadays cystic fibrosis-related diabetes (CFRD) is considered the most common complication associated with CF. It can appear as early as infancy or adolescence, and its prevalence can be as high as 50 percent in adult patients. Because of its high prevalence, difficulties in early detection and the risks involved, in recent years several studies and consensuses have focused on this condition, adding information about the epidemiology, pathophysiology, prognosis and treatment of CFRD. The main aspects of these new concepts, as well as the current recommendations for its diagnosis and follow-up, will be presented in this study.

Fibrose cística (FC) é a doença autossômica recessiva mais comum nos caucasianos. Avanços no tratamento da FC acarretaram aumento na sobrevida dos pacientes, que trouxe o aparecimento de comorbidades relacionadas à doença. Atualmente, o diabetes relacionado à fibrose cística (DRFC) é considerado a complicação mais comum associada à FC, podendo aparecer já na infância ou adolescência, chegando a atingir até 50 por cento dos pacientes adultos. Em virtude da alta prevalência, das dificuldades de diagnosticar precocemente e das graves consequências para os pacientes, nos últimos anos vem crescendo a preocupação com a detecção e o tratamento precoces do DRFC. Vários grupos têm se dedicado a procurar evidências e desenvolver consensos com o objetivo de orientar o diagnóstico e o acompanhamento dessa comorbidade. Neste artigo apresentamos os principais aspectos dessa evolução, bem como as atuais recomendações no acompanhamento de pacientes com DRFC.

TSH neurosecretory dysfunction (TSH-nd) in Down syndrome (DS): low risk of progression to Hashimoto's thyroiditis / Disfunção neurossecretora de TSH na síndrome de Down: baixo risco de progressão para a tireoidite de Hashimoto

INTRODUCTION: Patients with Down syndrome (DS) often have elevated TSH (hypothalamic origin), which is called TSH neurosecretory dysfunction (TSH-nd). In these cases, there is slight elevation in TSH (5-15 µUI/mL), with normal free T4 and negative thyroid antibodies (AB). OBJECTIVE: To recognize the risk of progression to Hashimoto's thyroiditis (HT). SUBJECTS AND METHODS: We retrospectively analyzed 40 DS patients (mean age = 4.5 years), followed up for 6.8 years. RESULTS: HT was diagnosed in 9/40 patients, three early in monitoring, and six during evolution. In 31/40 patients, TSH-nd diagnosis remained unchanged over the years, with maximum TSH values ranging from 5 to 15 µUI/mL. In this group, free T4 also remained normal and AB were negative. There was a significant TSH reduction (p = 0.017), and normal TSH concentrations (< 5.0 µUI/mL) were observed in 29/31 patients, in at least one moment. No patient had TSH > 15 µUI/mL. CONCLUSION: DS patients with TSH-nd present low risk of progression to HT (10 percent for females and 6 percent for males).

INTRODUÇÃO: Pacientes com síndrome de Down (SD) geralmente apresentam TSH elevado (de origem hipotalâmica), uma desordem chamada de disfunção neurossecretora de TSH (TSH-nd). Nesses casos, há uma leve elevação do TSH (5-15 µUI/mL), com T4 livre normal e anticorpos antitireoide (AB) negativos. OBJETIVO: Reconhecer o risco de progressão para a tireoidite de Hashimoto (HT). SUJEITOS E MÉTODOS: Analisamos retrospectivamente 40 pacientes com SD (idade média = 4,5 anos), acompanhados por 6,8 anos. RESULTADOS: A HT foi diagnosticada em 9/40 pacientes, três logo no início da avaliação e seis durante a evolução. Em 31/40 dos pacientes, o diagnóstico de TSH-nd permaneceu estável durante os anos, com valores máximos de TSH variando de 5 a 15 µUI/mL. Neste grupo, o T4 livre também permaneceu normal e os AB foram negativos. Houve uma redução significativa do TSH (p = 0,017), e concentrações normais de TSH (< 5,0 µUI/mL) foram observadas em 29/31 pacientes, em pelo menos um momento. Nenhum paciente apresentou TSH > 15 µUI/mL. CONCLUSÃO: Pacientes com SD e TSH-nd apresentam baixo risco de progressão para a HT (10 por cento para o sexo feminino e 6 por cento para o sexo masculino).

Near-final height in patients with congenital adrenal hyperplasia treated with combined therapy using GH and GnRHa / Altura quase normal em pacientes com hiperplasia adrenal congênita tratados com a combinação de GH e GnRHa

INTRODUCTION: Intrinsic limitations of glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) determine frequent loss in final height. The association of secondary central precocious puberty and early epiphyseal fusion is also frequent. In these conditions, GnRHa treatment alone or in combination with GH has been indicated. OBJECTIVES: This is a retrospective study, describing the estatural findings of CAH patients with significant decrease in height prediction, who were submitted to combined GH plus GnRHa therapy up to near-final height. SUBJECTS AND METHODS: We studied 13 patients, eight females and five males, eight with the classical and five with the nonclassical form of the disorder. Treatment with hydrocortisone (10-20 mg/m²/day) or prednisolone (3-6 mg/kg/day) was associated with GnRHa (3.75 mg/months) for 4.0 (1.5) years, and GH (0.05 mg/kg/day) for 3.6 (1.4) years. RESULTS: Stature standard deviation score for bone age improved significantly after GH treatment, becoming similar to target height at the end of the second year of GH treatment. CONCLUSION: We conclude that combined GH plus GnRHa therapy can be useful in a subset of CAH patients with significant reduction of predicted final height associated with poor hormonal control and central precocious puberty.

INTRODUÇÃO: As limitações intrínsecas da terapia com glicocorticoides em pacientes com hiperplasia adrenal congênita (HAC) frequentemente determinam menor altura final. Também é frequente a associação de puberdade precoce central secundária e fusão epifisária precoce. Nessas condições, tem sido indicado o tratamento com GnRHa sozinho ou em combinação com o GH. OBJETIVOS: Este é um estudo retrospectivo que descreve os achados de altura em pacientes com HAC que apresentavam diminuição significativa na altura predita e que foram submetidos ao tratamento combinado de GH com GnRHa até a altura quase normal. SUJEITOS E MÉTODOS: Estudamos 13 pacientes, oito do sexo feminino e cinco do sexo masculino, oito com a forma clássica e cinco com a forma não clássica da doença. O tratamento com hidrocortisona (10-20 mg/m²/dia) ou prednisolona (3-6 mg/kg/day) foi associado com GnRHa (3,75 mg/meses) por 4,0 (1,5) anos, e GH (0,05 mg/kg/dia) por 3,6 (1,4) anos. RESULTADOS: O escore de desvio-padrão da estatura para a idade óssea melhorou significativamente após o tratamento com GH, tornando-se similar à altura normal ao final do segundo ano desse tratamento. CONCLUSÃO: Concluímos que o tratamento de combinação com GH e GnRHa pode ser útil em um subgrupo de pacientes com HAC que apresentem redução significativa da altura final predita, associado com controle hormonal inadequado e puberdade central precoce.