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Objective: To look for technical simplification and economic efficiency in the treatment of pediatric diabetic ketoacidosis (DKA) with subcutaneous use of the fast-acting insulin analog (lispro) and compare its use with regular intravenous insulin treatment.Research Design and Methods: In this controlled clinical trial from June 2001 to June 2003, we randomized 60 episodes of DKA with a blood glucose level > or = 16.6 mmol/l (300 mg/dl), venous pH <7.3 and/or bicarbonate <15 mmol/l, or ketonuria greater than + +. Of the 60 episodes, 30 were treated with subcutaneous lispro (0.15 units/kg) given every 2 h (lispro group) and the other 30 cases received continuous intravenous regular insulin (0.1 unit x kg(-1) x h(-1); CIRI group). Volume deficit was repaired with 10-ml/kg aliquots of 0.9% sodium chloride. Laboratory monitoring included hourly bedside capillary glucose, venous blood gas, beta-hydroxybutyrate, and electrolytes. Plasma blood glucose levels were measured on admission, 2 h after admission, when capillary blood glucose reached < or = 13.8 mmol/l (250 mg/dl), and 6, 12, and 24 h thereafter.Results: Capillary glucose levels decreased by 2.9 and 2.6 mmol x l(-1) x h(-1) in the lispro and CIRI groups, respectively, but blood glucose fluctuated at different time intervals. In the CIRI group, metabolic acidosis and ketosis resolved in the first 6-h period after capillary glucose reached 13.8 mmol/l, whereas in the lispro group, they resolved in the next 6-h interval; however, both groups met DKA recovery criteria without complications.Conclusions: DKA treatment with a subcutaneous fast-acting insulin analog represents a cost-effective and technically simplified procedure that precludes intensive care unit admission. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a case study of the ABCC8 gene associated with hyperinsulinism.

Cystic fibrosis (CF) is a highly prevalent autosomal recessive disorder that is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene (7q31.2), which encodes the CFTR chloride-anion channel that is expressed in several tissues. Life expectancy has increased significantly over the past few decades due to therapeutic advances and early diagnosis through neonatal screening. However, new complications have been identified, including CF-related diabetes (CFRD). The earliest detectable glycemic abnormality is postprandial hyperglycemia that progresses into fasting hyperglycemia. CFRD is associated with a decline in lung function, impairments in weight gain and growth, pubertal development, and increased morbidity and mortality. Annual screening with oral glucose tolerance test is recommended beginning at the age of 10, and screenings are recommended for any age group during the first 48 h of hospital admission. Fasting plasma glucose levels ≥126 mg/dL (7.0 mmol/L) or 2-h postprandial plasma glucose levels ≥200 mg/dL (11.1 mmol/L) that persist for more than 48 h are diagnostic criteria for CFRD. Under stable health condition, the diagnosis is made when laboratory abnormalities in accordance with the American Diabetes Association criteria are detected for the first time; however, levels of HbA1c <6.5% do not rule out the diagnosis. Treatment for CFRD includes insulin replacement and a hypercaloric and hyperproteic diet that does not restrict carbohydrates, fats or salt, and diabetes self-management education. The most important CFRD complications are nutritional and pulmonary disease deterioration, though the microvascular complications of diabetes have already been described.

The International Diabetes Federation (IDF-2015) estimates the existence of 30,900 children under 15 years old with type 1 diabetes mellitus (DM1) in Brazil, and an increase of 3.0% per year is expected. This review focused on meta-analysis and pediatric diabetes update articles in order to draw attention to the need of planning coping strategies to support this serious public health problem in coming years. DM1 is considered an immuno-mediated disease with a complex transmission influenced by genetic and environmental factors responsible for a gradual destruction of the insulin producing pancreatic beta cells. Seroconversion to DM1-associated autoantibodies and abnormalities in metabolic tests that assess insulin secretion and glucose tolerance can be used as predictive criteria of beta cells functional reserve and the onset of the clinical disease. Symptomatic DM1 treatment is complex and the maintenance of good metabolic control is still the only effective strategy for preserving beta cell function. Disease duration and hyperglycemia are both risk factors for the onset of chronic vascular complications that negatively affect the quality of life and survival of these patients. In this regard, health teams must be trained to provide the best possible information on pediatric diabetes, through continuing education programs focused on enabling these young people and their families to diabetes self-management.

Thirty-two Brazilian families with MODY phenotype were screened for GCK and HNF1A mutations. GCK mutations were found in 8 families, all patients with mild asymptomatic hyperglycaemia; 3 of them are novel: p.Asp365Asn, p.Gly81Asp and p.Val253Leu. Previously described mutations in HNF1A were found in 2 families., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Carbohydrate counting (CHC) is ack - nowledged by the American Diabetes Association (ADA) as an important tool., Objective: To assess the efficacy of photographic educational materials to train adolescents with DM to perform CHC., Subjects and Methods: 76 adolescents were randomly divided into two groups of CHC orientation: by means of photographic materials (Photo) or by a list of foods (List). One month afterwards, the participants were contacted via telephone to answer questions on CHC to reinforce the training (Quiz). Two days after taking the quiz, required the participants to visit an experimental kitchen to observe food portions in natura and to respond to a questionnaire on the weights in grams or carbohydrate equivalents of these portions. Statistical significance was established at p < 0.05., Results: 54 adolescents completed the study (79.7% female), with 51.8% allocated to the Photo group and 48.1% to the List group. The mean age was 13.8 ± 2.0 years old, and the mean body mass index (BMI) was 21.0 ± 3.2 kg/m2. The participants had average of 7.9 ± 1.5 years of schooling, while their parents had 8.0 ± 3.8 years. The knowledge of CHC was similar in both groups before the intervention. After the intervention, the Photo group achieved a significantly higher hit difference on the CHC assessment test than the List group (Photo: 2.5 vs List: 1.0; p = 0.03)., Conclusions: The photographic educational material was more effective in helping adolescents with DM understand and learn to perform carbohydrate counting., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

We report a case of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to a novel DAX1 mutation. A 19-month-old boy with hyperpigmentation and failure to thrive came to our service for investigation. Three brothers of the patient had died due to adrenal failure, and a maternal cousin had adrenal insufficiency. Adrenoleukodystrophy was excluded. MRI showed normal pituitary and hypothalamus. Plasma hormone evaluation revealed high ACTH (up to 2,790 pg/mL), and low levels of androstenedione, DHEA-S, 11-deoxycortisol, and cortisol. At 14 years of age the patient was still prepubescent, his weight was 43.6 kg (SDS: -0.87) and his height was 161 cm (SDS: -0.36), with normal body proportions. In the GnRH test, basal and maximum values of LH and FSH were respectively 0.6/2.1 and < 1.0/< 1.0 U/L. Molecular investigation identified a novel mutation that consists of a deletion of codon 372 (AAC; asparagine) in exon 1 of DAX1. This mutation was not found in a study of 200 alleles from normal individuals. Prediction site analysis indicated that this alteration, located in the DAX1 ligand-binding domain, may damage DAX1 protein. We hypothesize that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient.

Objectives: To describe the presence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia (CAH); to evaluate the sensitivity and specificity of prostatic specific antigen (PSA) measured in congenital adrenal hyperplasia patients with regard to the detection of prostatic tissue in pelvic MRI., Methods: We studied 52 children and adolescents, 32 with the classical form of congenital adrenal hyperplasia, 10 boys and 10 girls without CAH. Pelvic MRI was performed in all patients to detect prostatic tissue. Prostate specific antigen, testosterone and dihydrotestosterone were measured in all patients. We used Receiver Operating Characteristic Curve for PSA discrimination capacity., Results: Five girls with congenital adrenal hyperplasia showed image of prostatic tissue on pelvic MRI. Prostate specific antigen showed sensitivity and specificity of 100% and 88.9%, respectively, taking 0.1 ng/mL as the cutoff level., Conclusions: The incidence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia was 15.6%. PSA demonstrated to be a good marker of prostatic tissue in these patients and should be used to screen patients to be submitted to image studies.

Objective: To determine which of two simplified blood glucose monitoring schemes promotes better metabolic control in type 1 diabetic patients during 12 months of participation in educational groups., Methods: A crossover clinical trial involving 21 patients divided into two groups was conducted. They were submitted to a two monitoring schemes: 2 alternate daily preprandial measurements and 2 alternate daily pre-and postprandial measurements. The effectiveness of the schemes was evaluated based on HbA1c. Variations in mean HbA1c were analyzed by Friedman test., Results: The groups were homogenous in terms of sociodemographic and clinical variables (p>0.05). Mean HbA1c levels ranged from 8.48 (+/-1.00) to 7.37 (+/-0.99) over time in Group A and from 9.89 (+/-0.86) to 8.34 (+/-1.06) in Group B. The analysis of the HbA1c showed a significant reduction in the first and last 6 months and over the 12 months of the study in two groups (p<0.05). The preprandial scheme demonstrated the largest number and highest percentage of significant drops in HbA1c., Conclusions: The two monitoring improved the metabolic control and the preprandial scheme was more effective.

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.

Cystic fibrosis-related diabetes (CFRD) is a major co-morbidity generally affecting patients over 15 years old and it is associated with increased morbidity and mortality. The pathophysiology includes exocrine tissue destruction, insulin deficiency and insulin resistance; the carbohydrate metabolism dysfunction begins with an altered kinetic in insulin secretion followed by a progressive insulin deficiency. Postprandial hyperglycemia is the first abnormality seen in CF patients and the classical symptoms of diabetes may not be recognized. The screening strategy proposed is annual random plasma glucose or fasting plasma glucose investigation, as well as the performance the oral glucose tolerance test (OGTT). Two categories of diabetes are related to CF: CFRD without fasting hyperglycemia (fasting glucose < 126 mg/dL and 2h OGTT glucose > 200 mg/dL) and CFRD with fasting hyperglycemia (fasting glucose > 126 mg/dL). Nutritional management and hyperglycemia control are the CFRD treatment goals. Insulin control is the standard medical therapy for CFRD with fasting hyperglycemia and the benefits of oral insulin secretagogue and sensitizing agents are still controversial.

Objective: Although it is type 1 diabetes mellitus of autoimmune origin that is most prevalent in childhood and adolescence, other forms of diabetes can also affect this population, resulting in different prognosis and treatment., Sources: Information was obtained by means of a bibliographic review, carried out by running searches for scientific articles in the MEDLINE and LILACS databases, in addition to classic publications on the subject, with the most representative being chosen., Summary of the Findings: This article discusses the pathophysiological mechanisms, clinical presentation and treatment of the various forms of diabetes that affect the pediatric age group, such as type 1 diabetes mellitus , type 2 diabetes mellitus, maturity-onset diabetes of youth, neonatal diabetes, mitochondrial diabetes, diabetes of generalized lipodystrophy, diabetes secondary to other pancreatic diseases, diabetes secondary to other endocrine diseases, diabetes associated with infections and cytotoxic drugs and diabetes related to certain genetic syndromes., Conclusions: Recognition of the primary pathophysiologic mechanism of the form of diabetes presented can guide specific treatment, optimizing metabolic control and minimizing complications over the long term.

The study analyzed the occurrence of hypoglycemia and metabolic control of two monitoring schemes in type-1 diabetic patients during 12 months they participated in education groups. Clinical crossed trials were conducted with 21 patients divided into two groups included the monitoring scheme proposed. Glycemic individuals' profiles directed monthly adjustments of insulin doses. The analyses were performed using Fisher, t-Student and Friedman's tests. There were no significant differences in hypoglycemia between the groups in any given month or scheme (p > 0.05). The comparisons within groups between insulin mean dose and HbA1c, and hypoglycemic episodes also did not show significant difference (p > 0.05). Metabolic control improved during the study in both groups, independently from the monitoring scheme (p < 0.05).

Nephrogenic diabetes insipidus (NDI) is an inherited disorder characterized by renal resistance to the antidiuretic effect of arginine vasopressin (AVP), resulting in polyuria, polydipsia, and hypoosmolar urine. In the vast majority of cases, NDI is associated with germ-line mutations in the vasopressin receptor type 2 gene (AVPR2) and in about 8% of the cases with the water channel aquaporin-2 gene (AQP-2) mutations. To date, approximately 277 families with 185 germ-line mutations in the AVPR2 gene have been described worldwide. In the present study, the AVPR2 gene was genotyped in eight unrelated Brazilian kindred with NDI. In five of these NDI families, novel mutations were noted (S54R, I130L, S187R, 219delT, and R230P), whereas three seemingly unrelated probands were found to harbor previously described AVPR2 gene mutations (R106C, R137H, R337X). Additionally a novel polymorphism (V281V) was detected. In conclusion, although NDI is a rare disease, the findings of mutations scattered over the entire coding region of the AVPR2 gene are a valuable model to determine structure function relationship in G-protein-coupled receptor related diseases. Furthermore, our data indicate that in Brazil the spectrum of AVPR2 gene mutations is "family specific".

Adrenocortical carcinoma is a rare condition with an unpredictable prognosis as a rule. The authors retrospectively analyzed the clinical outcome of 46 patients (31 F, 15 M) during 16 years building up a numerical index for the prognosis, based on clinical and immunohistochemical data. Four indices were analyzed: J1= (Y + 2L + 4H)/T; J2 = (J1) square root of W/200; J3 = (O + Y + 2L + 4H)/T; J4 = (J3) square root W/200. Y = 1 when chronological age (CA) >33 mo, Y = 0 when CA < or =33 mo; L = 1 for right sided tumor and L = 0 for left sided tumor; H = 1 in presence of hypertension and H = 0 for normal blood pressure; T = length of disease in months; W = weight of tumor (g); O = 1 in the absence of p53 protein and O = 0 in the presence of p53. The chance of bad prognosis was observed when age is >33 mo, tumor is on the right side, systemic hypertension is present, tumor weight >250 g, in the absence of p53, J1, J2, J3 >0.4 (p <0.001) and J4 >0.5 (p <0.01). Clinical data and the mathematical model enabled us to establish probabilities of good prognosis in 78-96% and bad prognosis in 63-83%.

Unlabelled: Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment., Patients and Method: The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy), and group C underwent chemotherapy plus radiotherapy (24 Gy). Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging., Results: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau) between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy). The final predicted height (Bayley-Pinneau) was significantly less (P = 0.0071) in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis., Conclusion: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.

Purpose: Two groups of girls with premature breast development were studied retrospectively. We tried to identify clinical, radiological, and hormonal parameters that could distinguish between a benign, nonprogressive premature thelarche and a true precocious puberty., Methods: The clinical outcome of 88 girls with breast enlargement before 6.1 years of age was analyzed. Taking into account the progression of their sexual maturation, we allocated the children into 2 groups: "Isolated Premature Thelarche" (n = 63) and "Precocious Puberty" (n = 25) groups. Chronological and bone ages, height and growth velocity centiles, computerized tomography of hypothalamus-pituitary area, pelvic ultrasonography, gonadotropin response to luteinizing hormone-releasing hormone stimulation as well as basal levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and prolactin were studied in both groups. Statistical analysis were performed using the Student t test to compare the sample means. Fisher's exact test and chi2 test were used to analyze the nonparametric variables., Results: Isolated premature thelarche most frequently affected girls younger than 2 years who presented exaggerated follicle-stimulating hormone response to luteinizing hormone-releasing hormone stimulation test. The precocious puberty group had higher initial stature, accelerated growth rate and bone age, increased uterine and ovarian volumes, high spontaneous luteinizing hormone levels by immunofluorimetric assay, as well as a high luteinizing hormone response and peak luteinizing hormone/follicle-stimulating hormone ratio after luteinizing hormone-releasing hormone stimulation., Conclusion: At initial presentation, girls who undergo true precocious puberty present advanced bone age, increased uterine and ovarian volumes in addition to breast enlargement, as well as an luteinizing hormone-predominant response after a luteinizing hormone-releasing hormone stimulation test.

Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency is a common autosomal recessive disorder resulting from mutations in the 21-hydroxylase (CYP21) gene. To develop a strategy to screen for the most commonly occurring CYP21 mutations in Brazil, we performed molecular genotype analysis on 73 children with CAH representing 71 unrelated families. The techniques used for CYP21 molecular genotype analysis were: restriction fragment length polymorphism, single-strand conformational polymorphism, allele-specific oligonucleotide hybridization, allele-specific polymerase chain reaction amplification, and heteroduplex analyses. Mutations were identified on all but eight affected alleles. The intron 2 splicing mutation was the most frequently identified mutation. Screening for the most common mutations detected at least one mutation on 132/142 (93%) alleles. Multiple CYP21 mutations were detected on 16.2% of alleles. The high frequency of multiple mutations on a single allele emphasizes the importance of thorough and accurate molecular genotype analysis of the complex CYP21 locus.

Forty consecutive patients with Ullrich-Turner syndrome (UTS) were followed-up and investigated for the presence of Y chromosome fragments in their genomes. We used the polymerase chain reaction (PCR) to detect SRY (sex-determining region on the Y chromosome) and the sequence-tagged sites (STS) sY57, sY59, sY85, sY94, sY124 and sY157--which correspond to regions 3C (sY57 and 59), 5C, 5G, 5P, and 6F, respectively, of the Y chromosome--searching for Y fragments that could bear the putative locus (loci) for gonadoblastoma (GBY). It has been shown that the presence of GBY greatly increases the risk of dysgenic gonads to undergo malignant transformation. Among our 40 patients, we found Y-derived sequences--including SRY and the region spanning from sY57 to sY94--in two. These two patients had a marker chromosome detected by conventional cytogenetic analysis (45,X/46,X + mar). Their gonads were excised and found to be streaks. In one of the patients, we found foci of primitive sex cords (amidst the gonadal stroma), oviducts and Wolffian remnants. Fluorescence in situ hybridization (FISH) did not show Y chromosome material in her gonad-derived fibroblasts. The other girl had hyperplastic Leydig cells in the gonadal stroma, oviducts and Wolffian remnants, with signs of epididymal differentiation. PCR assays performed on DNA extracted from paraffin-embedded gonadal tissue were negative for SRY sequences in both patients. These findings show that all UTS patients should be examined for Y chromosome material, and that positive cases should have their dysgenic gonads excised due to the high risk of malignancy.