Increased prevalence of early cochlear damage in young patients with type 1 diabetes detected by distortion product otoacoustic emissions.

OBJECTIVE: To evaluate the hearing of adolescents with diabetes mellitus type 1(DM1) by otoacoustic emissions (OAEs), and by comparing different tests with pure-tone audiometry to identify potential early cochlear impairments. DESIGN: Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAEs), and distortion product otoacoustic emissions (DPOAEs) were performed in a group of adolescents with and without DM1. Clinical characteristics, disease duration, and glycated haemoglobin levels were studied. STUDY SAMPLE: Participants were 40 adolescents with DM1 and 40 healthy subjects. RESULTS: Sensorineural hearing loss, affecting frequencies of 6000 and 8000 Hz, was found only in DM1 subjects when compared to the controls (7.7% vs. 0%, p < 0.05). A higher prevalence of cochlear damage was detected by DPOAE responses, 32% belonging from the diabetic group, vs. 3.7% in the control group. Absent TEOAE responses were observed in only three individuals, all from the diabetic group (5.1% of the tests performed in the diabetic group). Additionally, hearing thresholds were better in diabetic subjects with good control when compared to ones with regular or poor control (p = 0.00). Hearing thresholds were higher in poorly controlled diabetics when compared to subjects with good (p = 0.000) or regular control (p = 0.006). CONCLUSION: Early evidence of cochlear damage was detected in adolescents with DM1 leading to hearing loss at high frequencies. Abnormal DPOAEs responses were found more frequently than the alterations in TEOAEs and pure-tone audiometry, suggesting that DPOAEs evaluation is the most sensitive and it could be used for monitoring the progression of cochlear damage during the early stages of hearing impairment.

Association of preterm birth with poor metabolic outcomes in schoolchildren.

OBJECTIVE: To investigate, at school age, the metabolic profile of children born preterm. METHODS: A cross-sectional study of children 5 to 8 years old, born with gestational age (GA) < 34 weeks and/or weight ≤ 1,500 grams. Clinical and anthropometric data were assessed by a single trained pediatrician. Biochemical measurements were done at the organization's Central Laboratory using standard methods. Data on health conditions, eating, and daily life habits were retrieved from medical charts and through validated questionnaires. Binary logistic and linear regression models were built to identify the association between variables, weight excess, and GA. RESULTS: Out of 60 children (53.3% female), 6.8 ± 0.7 years old, 16.6% presented excess weight, 13.3% showed increased insulin resistance markers and 36.7% had abnormal blood pressure values. Those presenting excess weight had higher waist circumferences and higher HOMA-IR than normal-weight children (OR = 1.64; CI = 1.035-2.949). Eating and daily life habits were not different among overweight and normal-weight children. The small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA, 83.3%) birth weight children did not differ regarding clinical (body weight, blood pressure) or biochemical variables (serum lipids, blood glucose, HOMA-IR). CONCLUSION: Schoolchildren born preterm, regardless of being AGA or SGA, were overweight, and presented increased abdominal adiposity, reduced insulin sensitivity, and altered lipid profile, justifying longitudinal follow-up regarding adverse metabolic outcomes in the future.

Helicobacter pylori Infection Is Associated With Thyroid Dysfunction in Children With Congenital Hypothyroidism.

Helicobacter pylori (H. pylori) infection leads to a systemic low-grade inflammatory state and has been associated causally with a diverse spectrum of extra-gastric disorders. Among them, the infection has been involved in the pathogenesis of autoimmune thyroid disease (ATD), but only one study had evaluated children. Therefore, a cross-sectional study was conducted in a cohort of 142 children and adolescents, randomly assessed among those followed up for thyroid diseases in a university pediatric endocrinology service: 106 with congenital hypothyroidism (CH) and 36 with ATD. All children were asymptomatic, under strict control on levothyroxine replacement, and reported no other diseases or use of drugs. Helicobacter pylori status was evaluated by the 13C-Urea Breath Test (13C-UBT). Antithyroid antibodies (ATPO, antiTg, and TRAb) and serum thyroid hormones (TSH, free T4, and T3) were assessed by standard assays. Data were analyzed in logistic models by the SPSS statistical software package, and a p-value ≤ 0.05 was considered statistically significant. The prevalence of H. pylori infection was 19.44% in children with ATD. Neither the gender nor the serum levels of thyroid hormones and antithyroid antibodies were associated with the H. pylori-positive status. Thirty-seven (34.90%) children with CH were infected with H. pylori. The mean T3 serum level (3.59 ± 0.84) was significantly lower (p = 0.001) in the infected children than in those free from the infection (3.95 ± 0.89), association that remained after adjustment for the other variables in the multivariate analysis. Because no difference was observed in the levels of TSH and T4, the results indicate that the infection may lead to impairment in the thyroid hormonal balance, but not in the hypothalamic-pituitary-thyroid axis function. In as much as H. pylori infection is highly widespread and the prevalence of CH is also not negligible, additional studies are required to confirm our results and to identify the involved mechanisms.

Pharmacogenomic markers of glucocorticoid response in congenital adrenal hyperplasia.

Glucocorticoids (GC) replacement are the mainstay treatment for 21-hydroxylase deficiency (21-OHD), the most common cause of congenital adrenal hyperplasia (CAH), in its classical form. There are novel insights into the genetic basis of the GC action diversity that point to an important role for GC receptor (GR) gene polymorphisms, suggesting a possible modulation in occurrence of metabolic disorders, what may be relevant to clinical management of 21-OHD. The aim of this study was to investigate whether the five GR gene polymorphisms Tth111I, ER22, 23EK, BclI, 9ß (rs10052957, rs6189, rs6190, rs41423247, rs6198) and their combination into haplotypes are associated to different GC response in a cohort of classic 21-OHD subjects. GR genotype-phenotype associations were explored after a dexamethasone suppression test using very low-doses (VLD-DST), 20 and 40 µg/m². The final sample (n = 28) was selected based on the 102 individuals' previous genotypes classification, according to literature data of GC sensitivity or resistance. Thus, only patients with GC increased resistance (n = 18) or increased sensitivity (n = 10) profiles were selected. Out of 28 subjects aged 12 (2-34) years enrolled in this study, 75% were females, 75% presented the salt-wasting form (SW) and 25% the simple virilizing form (SV). Subjects who carried Tth111I and 9ß, associated or not to the ER22/23EK variants, showed an impaired DST response. Results did not differ significantly according to gender or body mass index. SV subjects with GC hypersensitivity-genotypes showed decreased average cortisol levels compared to those with GC resistance-genotypes (p = 0.0023). The Tth111I + 9ß/ Wild or Tth111I + ER22/23EK + 9ß/ Wild genotypes were associated to GC resistance in this population. This finding may be relevant given the challenges posed by therapeutic management with GC in CAH.

[Formula: see text]Socioeconomic aspects are crucial to better intellectual outcome in early-treated adolescents with congenital hypothyroidism.

Congenital hypothyroidism (CH) is an important cause of preventable intellectual disability. Implementation of CH neonatal screening programs leading to early treatment has improved cognitive outcome. However, more subtle cognitive impairments are still reported, and there is lack of clarity regarding factors that impact long-term cognitive outcome. Research to better understand these factors can lead to further improvements in the cognitive prognosis for these patients. The current study aimed to evaluate the cognitive performance of adolescents who were early-treated for primary permanent CH and possible associated variables. Neurocognitive evaluation was carried out in 66 adolescents, 11 to 16 years old: 34 with CH and 29 paired controls. Intellectual quotient (IQ), verbal fluency, processing speed, executive functions, and memory were investigated. CH patients and control subjects were comparable regarding sex, age, schooling, family's socioeconomic status and caregiver's educational level. Both groups presented not only similar IQ scores but also equivalent performances regarding Perceptual Reasoning, Working Memory and Processing Speed index scores. Patients presenting different CH etiologies (dysgenesis and dyshormonogenesis) showed similar cognitive performance. Socioeconomic aspects along with the initial levothyroxine dose were the main variables to positively influence the cognitive performance, the family's socioeconomic status having the strongest association with patients' cognitive skills.

Glucocorticoid receptor Gene (NR3C1) Polymorphisms and Haplotypes in patients with congenital adrenal hyperplasia.

BACKGROUND: Lifelong glucocorticoid (GC) replacement is the mainstay treatment of congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD). Challenges posed by therapeutic management of these patients are well known, but novel insights into the variability in clinical response to GC highlight a role for single nucleotide polymorphisms (SNPs) of the glucocorticoid receptor gene (NR3C1). AIM: To assess whether six commonly studied NR3C1 SNPs, which were previously associated with modified response to GC, are associated with CAH. We further assessed the linkage disequilibrium (LD) among these NR3C1 SNPs and their combination into haplotypes. METHODS: Genotypes were determined by Taqman allele discrimination assays for Tth111I (rs10052957), ER22 (rs6189), 23 EK (rs6190), N363S (rs56149945), BclI (rs41423247) and 9ß (rs6198) in a Brazilian cohort of 102 unrelated 21-OHD patients and 163 unrelated healthy subjects (controls). Haplotypes were estimated using Haplo.stats, and LD among SNPs using Haploview. RESULTS: Heterozygous subjects for Tth111I were more frequent in 21-OHD patients (P = 0.004), while heterozygous for BclI were more frequent in controls (P = 0.049). We found a strong LD among the six NR3C1 SNPs, and four out of six common haplotypes contained the Tth111I-variant. Although we found no significant differences in overall haplotype analysis, the BclI-haplotype was less frequent among 21-OHD patients (P = 0.0180). CONCLUSIONS: BclI-haplotype was less common and heterozygous for Tth111I were more frequent in 21-OHD patients, while heterozygous for BclI were more frequent in controls. Our novel findings may contribute to further clinical studies on the prognostic value of NR3C1 haplotypes towards individualized treatment for 21-OHD patients.

Risk factors for early onset of diabetic nephropathy in pediatric type 1 diabetes.

AIM: Diabetic nephropathy (DN) is a frequent complication in patients with long-standing type 1 diabetes mellitus (DM1). The objective of this study was to assess the prevalence of DN in DM1 patients diagnosed during childhood and its association with clinical and metabolic variables, such as age at diagnosis of DM1, glucose control, dyslipidemia, hypertension and the occurrence of diabetic retinopathy (DR). METHODS: The medical records of 205 patients admitted to the Pediatric Endocrinology Division at the Hospital das Clinicas da Universidade Federal de Minas Gerais, in Belo Horizonte, Brazil, were analyzed. For the analysis of survival and prognostic factors, the Kaplan-Meyer method and the COX regression model were used. RESULTS: The mean disease duration was 11.32 +/- 4.02 years and the mean age at diagnosis was 6.10 +/- 3.54 years. Microalbuminuria was present in 11.2% of them, proteinuria in 6.8% and end-stage renal disease (ESRD) in 2.9%. There was a significant association between the occurrence of microalbuminuria or proteinuria and poor glucose control (p=0.025 and p=0.005, respectively), higher LDL cholesterol levels (p=0.006 and p=0.004, respectively) and age greater than 6 years at diagnosis (p=0.049 and p=0.05, respectively). Proteinuria was also associated to the occurrence of DR (p=0.016). CONCLUSION: Our data showed that the prevalence of DN was higher than expected in this young population studied, especially considering the most severe forms. Clinical and laboratory factors associated to ND were: poor long-term glucose control, higher levels of LDL-C, higher age at diagnosis and the occurrence of DR.

INTIMA-MEDIA THICKNESS OF THE CAROTID ARTERIES IS AFFECTED BY PUBERTAL MATURATION IN HEALTHY ADOLESCENTS.

OBJECTIVE: To contribute to the assessment of normal parameters of carotid intima-media thickness (CIMT) in healthy adolescents. METHODS: A cross-sectional study was conducted through clinical, laboratory and ultrasound evaluation in 61 healthy adolescents. The inclusion criteria consisted of being in good health. The exclusion criteria were: presence or history of any chronic disease; being obese or overweight according to the World Health Organization (WHO) established criterion; continuous use of medication; or presenting a febrile condition or requiring medication within 48-hours prior to assessment. The pubertal stages were evaluated using the Tanner criteria. The high-resolution B-mode ultrasound examinations were performed according to the recommendations of the Consensus Statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. RESULTS: Adolescents were 14±2.6 years old, 62.3% female, 19 (31%) at early puberty (Tanner II and III), and 38 (62%) at late puberty (Tanner IV and V). They presented normal clinical and laboratorial parameters. CIMT values were 0.46±0.04 to 0.55±0.04 mm on the right and 0.48±0.02 to 0.53±0.04 mm on the left, according to pubertal maturation. CIMT values increased significantly on the right and left sides, according to pubertal stage (p<0.001 and p=0.016), and maximum internal diameters of the common carotid artery (p<0.025 and p<0.003). It was higher in males compared to females. CONCLUSIONS: An increase in CIMT in the healthy adolescents group, according to both age, and the degree of pubertal maturation should be considered when evaluating adolescents in diagnostic procedures.

Turner syndrome: searching for better outcomes.

OBJECTIVES: To assess the results of growth hormone on the growth of girls with Turner Syndrome and identify relevant parameters to improve outcomes. METHODS: Growth velocity and final height were studied in a historical cohort of 41 girls, regularly followed up for hormone distribution at three referral centers. The influence of oxandrolone and of estrogens on the final height was analyzed. The girls (initial chronological age=8.9+/-3.4years; initial bone age=7.0+/-3.1years) used 0.19 mg/kg/week of growth hormone for 4.0 +/- 2.0 years. RESULTS: In the first year, growth velocity increased by 71.5% in 41 girls and 103.4% in those who reached final height (11 girls). The whole group had a gain in the height SDS of 0.8 +/- 0.7 (p<0.01) and for those who reached a final height of 1.0 +/- 0.8 (p<0.01). Final height (143.6 +/-6.3 cm) was 3.9 +/- 5.3 cm higher than the predicted height, and the height gain occurred before estrogen therapy. Oxandrolone had no significant influence on height gain. The significant variables contributing to the final height were the duration of growth hormone used and its use prior to starting estrogens, the initial height SDS, and the growth velocity during the first year of treatment. CONCLUSIONS: We concluded that the use of growth hormone significantly increased the final height, which remained lower than the target. Results point to a need for starting growth hormone use as early as possible and to maximize treatment before estrogen replacement. It has been observed that even moderate doses of growth hormone may significantly increase early growth velocity.

Association of preterm birth with poor metabolic outcomes in schoolchildren

Abstract Objective: To investigate, at school age, the metabolic profile of children born preterm. Methods: A cross-sectional study of children 5 to 8 years old, born with gestational age (GA) < 34 weeks and/or weight ≤ 1,500 grams. Clinical and anthropometric data were assessed by a single trained pediatrician. Biochemical measurements were done at the organization's Central Laboratory using standard methods. Data on health conditions, eating, and daily life habits were retrieved from medical charts and through validated questionnaires. Binary logistic and linear regression models were built to identify the association between variables, weight excess, and GA. Results: Out of 60 children (53.3% female), 6.8 ± 0.7 years old, 16.6% presented excess weight, 13.3% showed increased insulin resistance markers and 36.7% had abnormal blood pressure values. Those presenting excess weight had higher waist circumferences and higher HOMA-IR than normal-weight children (OR = 1.64; CI = 1.035-2.949). Eating and daily life habits were not different among overweight and normal-weight children. The small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA, 83.3%) birth weight children did not differ regarding clinical (body weight, blood pressure) or biochemical variables (serum lipids, blood glucose, HOMA-IR). Conclusion: Schoolchildren born preterm, regardless of being AGA or SGA, were overweight, and presented increased abdominal adiposity, reduced insulin sensitivity, and altered lipid profile, justifying longitudinal follow-up regarding adverse metabolic outcomes in the future.

Abordagem da hiperplasia adrenal congênita pela deficiência da enzima 21-hidroxilase em crianças e adolescentes: revisão / Management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents: review

Objetivo: Descrever o diagnóstico e manejo clínico da deficiência da 21-hidroxilase (D-21OH), no contexto atual de inclusão da doença nos programas de triagem neonatal, bem como características genéticas, fisiopatológicas e manifestações na infância e adolescência. Fonte de Dados: Revisão integrativa realizada nas bases de dados MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science nos últimos vinte anos, em língua inglesa e portuguesa; população-alvo: crianças da primeira infância à adolescência; com o uso dos termos "triagem neonatal", "hiperplasia adrenal congênita", "deficiência da 21-hidroxilase", "glucocorticoide" e "polimorfismos do gene NR3C1". Síntese de Dados: A hiperplasia adrenal congênita (HAC) constitui um grupo de doenças caracterizadas por deficiências enzimáticas na esteroidogênese do córtex adrenal. A D-21OH é responsável por 95% dos casos e, se não tratada precocemente, pode levar ao óbito no período neonatal em sua forma clássica. A triagem neonatal para a HAC consiste na dosagem do precursor 17-hidroxiprogesterona (17OHP) no sangue de recém-nascidos, permitindo rápida confirmação diagnóstica e instituição da terapêutica. A implantação da triagem neonatal constitui um avanço, mas o controle dos pacientes pediátricos com D-21OH é complexo e deve ser sempre individualizado. Conclusão: A instituição dos programas de triagem neonatal para HAC tem trazido benefícios para o prognóstico das crianças com D-21OH. Seu manejo é multiprofissional, individualizado e ainda um desafio mesmo para o especialista. Ampla divulgação do conhecimento sobre a doença é desejável para permitir melhor condução dessas crianças, especialmente de meninas com a doença que apresentam genitália atípica.

Objective: To describe the diagnosis and clinical management of 21-hydroxylase deficiency (21OH-D), in the current context of including the disease in neonatal screening programs, as well as genetic, pathophysiological characteristics, and manifestations in childhood and adolescence. Data Source: Integrative review performed in MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science databases in the last twenty years, in English and Portuguese; target population: children from early childhood to adolescence; with the use of the terms "neonatal screening"; "congenital adrenal hyperplasia"; "21-hydroxylase deficiency"; "glucocorticoid"; "polymorphisms of the NR3C1 gene". Data Synthesis: Congenital adrenal hyperplasia (CAH) is a group of diseases characterized by enzyme deficiencies in adrenal cortex steroidogenesis. 21OH-D is responsible for 95% of cases and, if not treated early, can lead to death in the neonatal period in its classic form. Neonatal screening for CAH consists of measuring the precursor 17-hydroxyprogesterone (17OHP) in the blood of newborns, allowing rapid diagnostic confirmation and institution of therapy. The implementation of neonatal screening is an advance, but the control of pediatric patients with 21OH-D is complex and must always be individualized. Conclusion: The institution of newborn screening programs for CAH has benefits for the prognosis of children with 21OH-D. Its management is multi-professional, individualized and still a challenge even for the specialist. Wide dissemination of knowledge about the disease is desirable to allow better management of these children, especially girls with the disease who have atypical genitalia.

Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that?

INTRODUCTION: Oral corticosteroids (OCS) are a mainstay of treatment for asthma exacerbations, and short-term OCS courses were generally considered to be safe. Nevertheless, frequent short-term OCS courses could lead to hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Our study aimed at investigating the integrity of the HPA axis in children with persistent asthma or recurrent wheezing at the beginning of an inhaled corticosteroids (ICS) trial. METHOD: Morning basal cortisol was assessed just before the beginning of ICS, and 30, 60, and 90 days later, using Immulite® Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay (Los Angeles, USA; 2006). RESULTS: In all, 140 children (0.3-15 years old) with persistent asthma or recurrent wheezing have been evaluated and 40% of them reported short-term OCS courses for up to 30 days before evaluation. Out of these, 12.5% had biochemical adrenal suppression but showed adrenal recovery during a three-month ICS trial treatment. No significant differences were observed among children with or without adrenal suppression, neither in the number of days free of OCS treatment before cortisol evaluation (p=0.29) nor in the last OCS course duration (p=0.20). The number of short-term OCS courses reported in the year preceding the cortisol evaluation was also not different (p=0.89). CONCLUSION: Short-term systemic courses of corticosteroids at conventional doses can put children at risk of HPA axis dysfunction. ICS treatment does not impair adrenal recovery from occurring. Health practitioners should be aware of the risk of a blunted cortisol response upon exposure to stress during the follow-up of patients with persistent asthma or recurrent wheezing.

Imaging methods for bone mass evaluation during childhood and adolescence: an update.

The objective of the work was to prepare an update on imaging methods for bone evaluation during childhood and adolescence. The text was based on original and review articles on imaging methods for clinical evaluation of bone mass in children and adolescents up to 20 years old. They were selected from BIREME and PUBMED by means of the following keywords: bone density; osteoporosis/diagnosis; densitometry; tomography; ultrasonography; magnetic resonance imaging; and radiogrammetry and published in Portuguese or English, in the last 10 years (2006-2016). The article was organized into topics with the description of peculiarities, advantages and disadvantages of each imaging method and their possible clinical applicability. Despite the emergence of new technologies, dual energy X-ray absorptiometry (DXA) remains the gold standard method for low bone mass diagnosis in all age groups. However, interpretation is complex in children and adolescents and demands skilled people. Quantitative computed tomography (QCT) [central QCT, peripheral QCT (pQCT) and high resolution-pQCT (HR-pQCT)] and magnetic resonance imaging (MRI) evaluate real bone density, but are not yet available for routine use. Quantitative bone ultrasound (QUS) shows good perspectives for its use in primary prevention actions. Automated radiogrammetry shows promise as a method able to flag individuals who might benefit from a complete bone assessment, but the clinical value of the measures still needs to be established.

Increased carotid intima-media thickness in Brazilian adolescents with type 1 diabetes mellitus.

BACKGROUND: Increased carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is an independent predictor of future cardiovascular events, and has been reported in children with various chronic diseases, including type 1 diabetes mellitus (DM1). OBJECTIVES: Evaluate CIMT and its association with cardiovascular risk factors in Brazilian adolescents with DM1. METHODS: Cross-sectional study of 118 adolescents, 57 with DM1 and no chronic complications related to the disease, and 61 healthy individuals. Clinical, biochemical, and high-resolution B-mode ultrasonographic evaluations according to the Consensus Statement of the American Society of Echocardiography CIMT Task Force were performed. RESULTS: Adolescents with diabetes (66.6% female) were 14.5 ± 2.9 years old and had 9.0 ± 4.0 years of disease duration. The healthy adolescents (62.3% female) were 14.3 ± 2.6 years old. All the adolescents had blood pressure within their reference ranges. In 66% of DM1 adolescents the systolic blood pressure was >50th percentile. Increased CIMT was observed in adolescents with diabetes compared with those in the control group: 0.53 vs 0.51 mm (p < 0.004) on the right side, and 0.55 vs 0.51 mm (p < 0.001) on the left side. CIMT presented independent and positive associations with diabetes duration, total cholesterol level, low-density lipoprotein cholesterol level, and systolic blood pressure percentile in DM1 adolescents. CONCLUSIONS: Increased CIMT was observed in young Brazilian adolescents with DM1, and was associated with cardiovascular risk factors. CIMT assessment may be useful for the early identification and monitoring of cardiovascular risk in this age group.

High prevalence of diabetic polyneuropathy in a group of Brazilian children with type 1 diabetes mellitus.

OBJECTIVE: To evaluate the prevalence of diabetic polyneuropathy (DNP) in children and adolescents with type 1 diabetes mellitus (DM1), and to compare the diagnostic criteria for DNP proposed and most widely utilized in the literature. METHODS: Forty-eight patients with DM1 with a mean age of 12.9 years and mean duration of DM1 of 7 years, and 14 controls, were compared. Results of clinical neurological examination and nerve conduction (NC) were compared by means of diagnostic criteria proposed at the San Antonio Conference and by Dyck et al. RESULTS: Twenty-two patients (46%) had DNP by the San Antonio criteria, and 25% according to those of Dyck et al. Three patients (6.3%) presented neurological complaints, such as lower limb pain, paresthesia and hyperhidrosis, and 31 (64.6%) presented peripheral nervous system changes upon clinical examination. Twenty-nine patients (60.4%) presented changes in motor and sensory nerve conduction. Motor NC changes were the most prevalent, above all in the median (86.2%) and fibular (55.2%) nerves. CONCLUSIONS: A high percentage of neurological changes were detected in this young population, with 5-10 years duration of DM1. Prevalence of DNP in the pediatric age group ranges from zero to 54% in published studies, mainly using the criteria of Dyck et al. or similar criteria. In the present study we found that roughly one-quarter of patients would be misdiagnosed according to the criteria utilized. We propose that neurological evaluation must be included in routine care for children with DM. Further studies leading to a more accurate diagnosis of DNP in children and adolescents are still necessary.

[Total urogenital sinus mobilization in the repair of ambiguous genitalia in children with congenital adrenal hyperplasia]. / Mobilização total do seio urogenital para tratamento da genitália ambígua em crianças com hiperplasia adrenal congênita.

The surgical approach to patients with congenital adrenal hyperplasia (CAH) has been a challenge and it is still controversial. The aim of this study was to review 10 children with 46,XX CAH who underwent one-stage total urogenital sinus mobilization (TUM). Age at operation ranged from 11 to 78 months (mean= 32) and the follow-up from 15 to 36 months (mean= 26). Cosmetic results were good in 7 patients and satisfactory in 3. After a mean follow-up of 26 months, our results showed that TUM was a good option to repair ambiguous genitalia in children with CAH.

[Growth rate of children with congenital adrenal hyperplasia during treatment with low doses of hydrocortisone]. / Ritmo de crescimento de crianças com hiperplasia congênita da supra-renal em tratamento com baixas doses de hidrocortisona.

We evaluated linear growth of 27 children with congenital adrenal hyperplasia (CAH) treated with low doses of oral hydrocortisone. They were followed-up during 6.1 +/- 1.8 years with daily hydrocortisone doses of 10.84 +/- 2.0 mg/m2 and 0.1 mg fludrocortisone (24 of them). Twenty-three were female. Mean chronological age (CA) was 6.1 +/- 2.9 years and bone age (BA) 6.9 +/- 3.3 (r = 0.66) at the beginning of the study. Five children showed BA advancement > 2 years relating to CA. It was calculated Height SD for CA (SD/H) and for BA (SD/BA) were calculated using NCHS as reference pattern. At the beginning of the study SD/H was -0.8 +/- 1.9 and corresponding SD/BA was -1.5 +/- 2.1; at the end SD/H was -0.17 +/- 1.5 and SD/BA was -1.34 +/- 1.2 (p = 0.02 and p = 0.51, respectively for the beginning and the end). BA changed 1.3 +/- 0.3 per year during this period. Children with advanced BA showed an improvement of SD/BA, from -4.55 +/- 0.9 at from the beginning, -4.55 +/- 0.9 to -2.48 +/- 0.4 at the end of follow-up, -2.48 +/- 0.4 (p = 0.003). The elevated plasma levels of 17-OH Progesterone (17OHP) and androstenedione showed further increase during follow-up. We conclude that children with CAH receiving low doses of hydrocortisone showed adequate growth during the follow-up, without excessive BA advancement, even though full suppression of plasma levels of 17OHP and androgens wasere not achieved.

Análise das emissões otoacústicas transitórias por banda de frequência em adolescentes com diabetes mellitus tipo 1 / Transient otoacoustic emissions analysis by frequency bands in adolescents with type 1 diabetes mellitus

Introdução: A associação entre perda auditiva e Diabetes Mellitus tipo 1 (DM1) é ainda pouco estudada. A perda auditiva é uma das complicações crônicas relacionadas ao grau de controle glicêmico, que os pacientes podem apresentar com a progressão da doença. Objetivo: Investigar o comprometimento auditivo por meio das emissões otoacústicas transitórias (EOAT) por banda de frequência em adolescentes com DM1 e relação com o controle glicêmico. Métodos: Foram incluídos 80 adolescentes, 50% do gênero masculino, entre 10 e 19 anos de idade: 40 com DM1 e 40 controles saudáveis, pareados por gênero e idade. Os dados clínicos e laboratoriais foram pesquisados nos prontuários médicos. O controle glicêmico foi avaliado por meio dos exames de hemoglobina glicada e os pacientes com DM1 analisados de acordo com o controle glicêmico. A avaliação auditiva foi realizada por meio da imitanciometria, audiometria, e posteriormente EOAT, em sala tratada acusticamente, pelo protocolo "TE Test" de clique não-linear (1 KHz a 4 kHz) a 80 dB NPS de intensidade (AuDX - Biologic). Resultados: As respostas às EOAT foram ausentes em 5,12% em pacientes com DM1, com diferença significativa em relação aos controles (p=0,04). A análise das EOAT por bandas de frequência mostrou maior proporção de alteração nos adolescentes com DM1 mal controlados quando comparados aos bem controlados, nas frequências de 1000Hz, 2000Hz e 3000Hz (p<0,05). Conclusão: As EOAT por bandas de frequência permitiram a identificação precoce de comprometimento auditivo em adolescentes com DM1 e mostraram associação entre DM1 mal controlado e perda auditiva. (AU)

Introduction: The association between hearing loss and type 1 diabetes mellitus (DM1) is still poorly studied. Hearing loss is one of the chronic complications related to the degree of glycemic control that patients may present with the progression of the disease. Objective: To investigate auditory impairment through transient otoacoustic emissions (TEOAE) by frequency band in adolescents with DM1 and in relation to glycemic control. Methods: Were included 80 adolescents, 50% males, between 10 and 19 years of age: 40 with DM1 and 40 healthy controls, matched by gender and age. Clinical and laboratory data were taken from the medical records. Glycemic control was evalueted by glycated hemoglobin and the patients with DM1 were analyzed according to glycemic control. To the auditory evaluation were used the immittance and audiometry, and the TEOAE. The test was performed in the acoustically treated room, the non-linear TE test protocol (1 KHz to 4 kHz) at 80 dB SPL (AuDX - Biologic ). Results: TEOAE responses were absent in 5.12% of patients with DM1, with a significant difference in relation to controls (p = 0.04). The analysis of TEOAE by frequency bands showed a higher proportion of alteration in adolescents with DM1 poorly controlled when compared to well controlled ones, in the frequencies of 1000Hz, 2000Hz and 3000Hz (p <0.05). Conclusion: TEOAE by frequency bands allowed the early identification of auditory impairment in adolescents with DM1 and showed an association between poorly controlled DM1 and hearing loss. (AU)

Cardiovascular risk factors and increased carotid intima-media thickness in young patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: Increased arterial intima-media thickness has been observed in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). CAH has also been associated with obesity, insulin resistance, and hypertension. The aim of the present study was to compare youths with CAH with healthy, normal-weight individuals, evaluating carotid intima-media thickness (CIMT) and indicative factors of cardiovascular risk to seek for abnormalities in the CAH group. SUBJECTS AND METHODS: Clinical, biochemical, and ultrasonographic evaluations, according to published criteria, were performed in 113 subjects (5 to 20 years old): 40 patients with 21-OHD and 73 healthy individuals matched for gender, pubertal status, and age. RESULTS: Most CAH patients were female (80%), salt-losers (72.5%), and pubescent (80%); 10 (25%) patients were overweight. An increase in CIMT was observed both on the right (p = 0.0240) and left (p = 0.0003) sides in 38 CAH patients compared with the healthy individuals. The body mass index, BMI/age Z score, and systolic blood pressure (SBP) were higher in patients compared with controls (p < 0.000 and p = 0.0219, respectively). CONCLUSIONS: Findings of increased CIMT, BMI, and SBP in young patients with 21-OHD indicate the need for early identification and intervention regarding cardiovascular risk. Validating these findings might result in improved therapeutic approaches for children with 21-OHD in the future.

Clinical and molecular data from 61 Brazilian cases of Congenital Hyperinsulinemic Hypoglycemia.

OBJECTIVE: To study the clinical and molecular characteristics of a sample of Brazilian patients with Congenital Hyperinsulinemic Hypoglycemia (CHH). METHODS: Electronic message was sent to members from Endocrinology Department- Brazilian Society of Pediatrics requesting clinical data for all cases of CHH. A whole blood sample from living patients was requested for DNA extraction followed by a search for mutations of the genes ABCC8, KCNJ11, GCK, GLUD1, HADH, SLC16A1 and HNF4A. RESULTS: Of the 61 patients evaluated, 36 (59%) were boys, and only 16 (26%) were born by normal delivery. Gestational age ranged from 32 to 41 weeks (mean = 37 weeks and 6 days). Birth weight ranged from 1590 to 5250 g (mean = 3430 g). Macrossomia occurred in 14 cases (28%). Age at diagnosis ranged from 1 to 1080 days (mean = 75 days). DNA for molecular analysis was obtained from 53 of the 61 patients. Molecular changes in the ABCC8 gene were detected in 15 (28%) of these 53 cases, and mutations in the KCNJ11 gene were detected in 6 (11%). Mutations in the GLUD1 gene were detected in 9 cases (17%) of the total series. Mutations of the GCK gene in heterozygosis were detected in 3 cases. No mutations were detected in the sequencing of genes HADH, SLC16A1 and HNF4A. CONCLUSION: The present study conducted in Brazil permitted the collaborative compilation of an important number of CHH cases and showed that the present clinical and molecular data are similar to those of published global series.