Abstract Objective: The main growth hormone action is to promote linear growth increasing protein synthesis stimulation and osteoblastic activity. Peak bone mass extends from adolescence to 30 years of age. Several factors may influence this acquisition and prevent fracture risk in adulthood, such as genetic potential, GH, ethnicity, and lifestyle factors. This study aims to compare bone mass and osteometabolic profile of white and Afro-descendant Brazilian adolescents in the transition phase, who were treated with human recombinant growth hormone in childhood. Methods: The authors selected 38 adolescents from the Transition Outpatient Clinic of the University of São Paulo. Lumbar spine and total body bone mineral density (BMD) and bone mineral content (BMC), serum calcium, 25-OH-vitamin D and bone markers were analyzed at the rhGH withdrawal. Results: The mean age was 16.8 ± 1.6 years. There were 21 Afro-descendant and 17 whites. Thirty-four percent of the sample presented vitamin D insufficiency, 66% inadequate calcium intake and 44.7% physical inactivity. The Afro-descendants showed a lower lumbar spine and total body Z scores than those of the whites (p = 0.04 and p = 0.03, respectively), as well as their mean body weight (p = 0.03). There were no differences in the remaining osteometabolic parameters. Conclusion: As most adolescents had vitamin D insufficiency, low calcium intake, and physical inactivity, calcium, and cholecalciferol supplementation and lifestyle changes should be encouraged. The Brazilian Afro-descendant may be a vulnerable group for low bone mass, requiring

ABSTRACT Obesity is a complex and multifactorial disease that is influenced by physiological, environmental, socioeconomic, and genetic factors. In recent decades, this serious disease has impacted a large number of adolescents as a result of lifestyle factors. A lack of exercise and the consumption of excessive calories from an inadequate diet are the main contributors to adolescent obesity. However, genetic and hormonal factors might also play a role. The short- and long-term consequences of this disease include chronic issues such as type 2 diabetes and cardiovascular disorders and an increase in early mortality rates. Although it is a serious disease, obesity in adolescents can be controlled with diet and exercise. When these lifestyle changes do not obtain the expected results, we can intensify the treatment by adding medication to the practice of diet and exercise. Additionally, for more severe cases, bariatric surgery can be an option. The purpose of this review is to clarify the current epidemiology, risks, and comorbidities and discuss news about the main treatments and the necessary improvements in this context.

RESUMO Objetivo: Descrever um caso de cirurgia bariátrica como tratamento de pseudotumor cerebral primário (PTCP) em adolescente do sexo masculino com obesidade. Descrição do caso: Adolescente, sexo masculino, 16 anos e 6 meses, com obesidade exógena [peso:133,6 kg; estatura:1,74 m (escore z: +0,14); IMC: 44,1 kg/m2 (escore z: +4,4)], estadiamento puberal de Tanner 5, apresentando cefaleia bi-parietal, pulsátil e de alta-intensidade, cerca de cinco vezes por semana, associada a despertares noturnos, e com melhora parcial com analgésicos comuns, há três meses. A avaliação oftalmológica evidenciou papiledema bilateral e a tomografia computadorizada de crânio não revelou massas ou alterações anatômicas. A punção lombar mostrou pressão intracraniana elevada de 40 cmH2O (Referência: <28 cmH2O) com conteúdo normal. Feito o diagnóstico, o paciente foi iniciou uso de acetazolamida. No entanto, após 3 meses, o paciente mantinha-se sintomático. Ele foi diagnosticado com obesidade devido ao consumo calórico excessivo e, como não havia obtido sucesso na perda de peso com tratamento clínico convencional, a cirurgia bariátrica foi indicada. Aos 16 anos e 9 meses, o paciente foi submetido a gastrectomia vertical laparoscópica sem complicações. A avaliação oftalmológica, cinco meses após a cirurgia, revelou melhora do papiledema bilateral com acuidade visual normal em ambos os olhos. Apresentou perda de excesso de peso de 67,5% (peso: 94,5 kg e IMC:31,2 kg/m2) e resolução completa dos sintomas de PPTC 18 meses após a cirurgia. Comentários: O PTCP é caracterizado pelo aumento da pressão intracraniana, sem evidência de deformidade ou obstrução do sistema ventricular na neuroimagem. Está associado à obesidade. A cirurgia bariátrica pode ser uma alternativa terapêutica válida para pacientes adolescentes obesos graves com sintomas refratários.

ABSTRACT Objective: To describe a case of a male adolescent with symptomatic idiopathic intracranial hypertension (IIH) associated with obesity treated with bariatric surgery. Case description: A 16-year-and-6-month-old severely obese boy [weight: 133.6 kg; height: 1.74 m (Z score: +0.14); BMI: 44.1 kg/m2 (Z score: +4.4)], Tanner pubertal stage 5, presented biparietal, high-intensity, and pulsatile headaches, about five times per week, associated with nocturnal awakenings, and partial improvement with common analgesics, for three months. Ophthalmologic evaluation evidenced bilateral papilledema. Cranial computed tomography revealed no mass or anatomic abnormalities. Lumbar puncture showed increased intracranial pressure of 40 cmH2O (reference value: <28 cmH2O) with a normal content. After being diagnosed with IIH, the patient was started on acetazolamide. However, after three months, he was still symptomatic. He was diagnosed with obesity due to excess energy intake and, as he had failed to lose weight after a conventional clinical treatment, bariatric surgery was indicated. The patient (at 16 years and nine months) underwent an uncomplicated laparoscopic sleeve gastrectomy. Ophthalmologic evaluation, performed five months after surgery, revealed normal visual acuity in both eyes and improvement of bilateral papilledema. Follow-up at 18 months showed a 67.5% loss of excess weight (weight: 94.5 kg and BMI: 31.2 kg/m2) and complete resolution of IIH symptoms. Comments: IIH is characterized by increased intracranial pressure with no evidence of deformity or obstruction of the ventricular system on neuroimaging. It has been associated with obesity. Bariatric surgery may be a valid alternative approach for morbidly obese adolescent patients with refractory symptoms.

SUMMARY Short bowel syndrome (SBS) is the leading cause of intestinal failure in children, a condition of absence of sufficient bowel to meet the nutritional and metabolic needs of a growing individual. The treatment of patients in this situation is based on the association of parenteral and enteral nutrition for prolonged periods of time until intestinal rehabilitation occurs with complete enteral nutrition autonomy. Six consecutive cases of children with SBS (residual intestinal length of 5 cm to 75 cm) were managed with this program and were diagnosed with associated hypothyroidism during the treatment (ages at the diagnosis 5 months to 12 years). All patients were successfully treated with oral hormone reposition therapy and in one patient, the replacement was performed via rectal enemas due to a complete absence of small bowel. Although iodine deficiency associated to long-term parenteral nutrition is a well-known condition, this is the first report in the literature about an expressive number of patients with hypothyroidism detected in patients with SBS during the prolonged treatment for intestinal rehabilitation.

RESUMO Objetivo: Realizar uma revisão sobre a Síndrome de Prader-Willi (SPW) com base nas publicações mais recentes e fornecer recomendações ao pediatra geral para diagnóstico precoce e seguimento. Fonte de dados: Artigos publicados nas bases Pubmed e SciELO. A pesquisa não foi limitada a um período e incluiu todos os artigos das bases de dados. Síntese dos dados: A SPW é uma síndrome genética rara, resultante da perda do imprinting gênico expresso no cromossomo paterno 15q11-q13, sendo caracterizada por alterações endocrinológicas, como deficiência de hormônio de crescimento, obesidade, insuficiência adrenal central, hipotireoidismo, hipogonadismo, além de alterações comportamentais e déficit intelectual. Há outras comorbidades associadas, como distúrbios de sono, escoliose, constipação, problemas dentários e alterações de coagulação. O protocolo de seguimento da SPW do Instituto da Criança da Universidade de São Paulo se baseia em quarto pilares principais: dieta, exercício físico, terapia com hormônio de crescimento humano recombinante (rhGH) e manejo comportamental e cognitivo. A dieta deve ser restrita a 900 kcal/dia, de acordo com a Pirâmide Alimentar do Prader-Willi, e o exercício físico deve ser diário, aeróbico e postural. A terapia com rhGH é fortemente recomendada pela literatura científica internacional e deve ser iniciada assim que for realizado o diagnóstico da síndrome. O manejo do comportamento é realizado com estratégias para estabelecer rotina e regras. Conclusões: Se a SPW se tornar mais familiar ao pediatra geral, o diagnóstico e o tratamento começarão mais precocemente, o que irá melhorar a qualidade de vida e os cuidados desses pacientes.

ABSTRACT Objective: To carry out a review about Prader-Willi Syndrome based on the most recent data about the subject and to give recommendation for the general pediatricians for early diagnoses and follow-up. Data sources: Scientific articles in the PubMed and SciELO databases. The research was not limited to a specific time period and included all articles in such databases. Data synthesis: The Prader-Willi Syndrome (PWS) is a rare genetic disorder resulting from the loss of imprinted gene expression within the paternal chromosome 15q11-q13. PWS is characterized by endocrine abnormalities, such as growth hormone (GH) deficiency, obesity, central adrenal insufficiency, hypothyroidism, hypogonadism and complex behavioral and intellectual difficulties. PWS individuals also may present other comorbidities, such as sleep disorders, scoliosis, constipation, dental issues and coagulation disorders. The follow-up protocol of the Children’s Institute at Universidade de São Paulo is based on four main pillars: diet, exercise, recombinant human growth hormone (rhGH) therapy and behavioral and cognitive issues. The diet must include a caloric restriction of 900 kcal/day, according to the Prader-Willi Eating Pyramid and exercise plan is focused on daily aerobic exercises and postural therapy. The rhGH therapy is highly recommended by the international scientific literature and must be started as soon as the diagnostic is made. The management of behavioral issues is based on strategies to establish routine and rules. Conclusions: If the general pediatrician becomes more familiar with PWS, the diagnosis and treatment will start earlier, which is essential to improve the quality of life and care for these individuals.

Abstract Aims: The aim of this study was to verify body composition, cardiorespiratory fitness, and biochemical markers of prepubertal overweight and obese boys to a 16-week futsal training program. Methods: Sixteen boys (age: 7-10 y, body mass index>thanat 95th percentileaccording to Center for Disease Control and Prevention; 35.5±7.4 percent fat) participated to futsal training program. The assessment of body composition was estimated using skinfold thickness, and the following variables were evaluated: total body mass, body mass index, body fat percentage, and lean body mass. Aerobic fitness measurementwas performed by gas exchange analysis in treadmill. In addition, an evaluation of the biochemical profile was conducted: triglycerides, total cholesterol, low density lipoprotein cholesterol, high-density lipoprotein cholesterol, plasma concentrations of glucose, and insulin. The futsal intervention included 60-min sessions performed two times/week. The mean intensity during training was between 57 to 88% of maximal heart rate of the age-predicted. Individual portable heart rate monitor controlled training intensity. Results: Significant increases in total body mass (4%), height (3%), lean body mass (8%), and significant 6%-decrease in body fat percentage was observed. Body mass index remained unchanged. Maximal oxygen uptake was elevated (p<0.018) by 11%. Biochemical markers were not modified after intervention. No association was found between body composition and metabolic variables. The effect size of futsal training on most variables was small (<0.5). Conclusion: Controlled intensity and adherence to this 16-week futsal training program were determinant to enhance body composition, and cardiorespiratory fitness in this group of prepubertal boys.

ABSTRACT Objective: The objective was to conduct clinical and metabolic evaluations of obese adolescents before and after laparoscopic sleeve gastrectomy (LSG) (up to 24 months). Subjects and methods: This was designed as a retrospective, descriptive series of cases study, conducted in Instituto da Criança, São Paulo, Brazil. Analysis of clinical and laboratory data from 22 obese adolescents between 14 and 19 years old submitted to LSG between 2007 and 2014. Patients had BMI > 40 kg/m2 or BMI > 35 kg/m2 with comorbidities. Anthropometric, clinical and laboratory assessments were performed: before surgery, 6, 12, 18, and 24 months after surgery. We assessed weight loss and metabolic changes up to 24 months after LSG. Results: The mean preoperative weight and BMI were 128.5 kg (SD = 23.1) and 46.5 kg/m2 (SD = 74), respectively. There was an average weight loss of 34.5 kg in the first 12 months’ post LSG, corresponding to a 60% excess weight loss (EWL), as well as an average reduction in BMI of 12.3 kg/m2. However, after 24 months, the average EWL was 45%, corresponding to an average weight regain (WR) of 13.3 kg (15%) within two years. LSG improved dyslipidemia in 67.8% of patients, a significant remission of hepatic steatosis 47% and 37.7% systemic arterial hypertension; type 2 diabetes remission was complete. Conclusions: LSG proved to be a safe and effective procedure and seems to be the new hope for the obesity epidemic.

ABSTRACT Aromatase is a cytochrome P450 enzyme (CYP19A1 isoform) able to catalyze the conversion of androgens to estrogens. The aromatase gene mutations highlighted the action of estrogen as one of the main regulators of bone maturation and closure of bone plate. The use of aromatase inhibitors (AI) in boys with short stature has showed its capability to improve the predicted final height. Anastrozole (ANZ) and letrozole (LTZ) are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450. In this review, we describe the pharmacokinetic profile of both drugs, discussing possible drug interactions between ANZ and LTZ with other drugs. AIs are triazolic compounds that can induce or suppress cytochrome P450 enzymes, interfering with metabolism of other compounds. Hydroxilation, N-dealkylation and glucoronidation are involved in the metabolism of AIs. Drug interactions can occur with azole antifungals, such as ketoconazole, by inhibiting CYP3A4 and by reducing the clearance of AIs. Antiepileptic drugs (lamotrigine, phenobarbital, and phenytoin) also inhibit aromatase. Concomitant use of phenobarbital or valproate has a synergistic effect on aromatase inhibition. Therefore, it is important to understand the pharmacokinetics of AIs, recognizing and avoiding possible drug interactions and offering a safer prescription profile of this class of aromatase inhibitors. Arch Endocrinol Metab. 2017;61(3):391-7.

Resumo A Federação Internacional de Diabetes (IDF-2015) estima a existência no Brasil de 30.900 menores de 15 anos portadores de diabetes mellitus tipo 1 (DM1), com previsão de aumento de 3,0% ao ano. Esta revisão buscou artigos de metanálise e atualização em diabetes infantil com o objetivo de alertar para a necessidade do planejamento de estratégias de enfrentamento deste que tende a ser um sério problema de saúde pública para os próximos anos. O DM1 é considerado uma doença imunomediada de transmissão complexa, influenciada por fatores genéticos e ambientais determinantes da destruição gradual das células beta pancreáticas produtoras de insulina. A positividade sorológica dos autoanticorpos associados ao DM1 e a alteração de testes metabólicos que avaliam a secreção de insulina e o estado glicêmico podem ser utilizados como critérios de previsão da reserva funcional de células beta e do início clínico da doença. O tratamento do DM1 sintomático é complexo, e a manutenção do bom controle metabólico é ainda a única estratégia efetiva de preservação das células beta ainda funcionantes. Tempo de duração da doença e hiperglicemia são fatores de risco para a instalação das complicações vasculares crônicas, que afetam negativamente a qualidade de vida e a sobrevida desses indivíduos. Torna-se necessária a formação de equipes de saúde preparadas para fornecer a melhor informação possível em diabetes infantil, através de programas de educação continuada, com potencial de capacitar esses jovens e suas famílias para o autocuidado.

Summary 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.

Objective To compare the two anthropometric standards for screening of overweight and cardio-metabolic risk in 6–10-year-old children.Subjects and methods This cross-sectional study included 175 subjects attending the Referral Center for the Treatment of Children and Adolescents in Campos, Rio de Janeiro. They were classified according to CDC and WHO BMI z scores as normal-weight (z-score > –1 and < 1), overweight (z-score ≥ 1 and < 2) or obese (z-score ≥ 2). Sensitivities and specificities in predicting systolic (SBP), diastolic (DBP) blood pressure and homeostatic model assessment insulin resistance index (HOMA-IR) alterations were calculated.Results There was a major difference in 11 children who rated overweight by the CDC but were reclassified as obese by the WHO. Their mean z-scores for SBP (1.71 ± 1.54), DBP (2.64 ± 1.83) and HOMA-IR (1.84 ± 0.98) were higher than those classified as overweight by both references (SBP = 0.49 ± 1.34, p < 0.023, DBP = 1.45 ± 0.97, p < 0.04 and HOMA = 1.24 ± 0.67, p < 0.04), but were similar to those classified as obese by both criteria (SBP = 1.25 ± 2.04, p = 0.60, DBP = 1.94 ± 1.19, p = 0.50 and HOMA = 2.09 ± 1.12, p = 0.76).Conclusion the 2007 WHO reference was the most sensitive in screening for overweight and alterations in blood pressure and HOMA-IR in 6–10-year-old children. Arch Endocrinol Metab. 2015;59(3):220-5

Objetivo : Avaliar o efeito da sibutramina na perda de peso de adolescentes obesos.Sujeitos e métodos : Estudo duplo-cego placebo controlado tipo cross over com duração de 13 meses. Foram incluídos no estudo 73 adolescentes obesos de ambos os sexos com idades entre 10 e 18 anos. A avaliação antropométrica foi realizada a cada 40 dias em média. Os exames laboratoriais e de imagem foram realizados antes, no período de wash-out e ao final dos 13 meses.Resultados : A porcentagem de pacientes que perderam 10% do peso inicial no placebo foi de 46% e, no grupo sibutramina, foi de 75%. Quando usaram o placebo, o peso em média se elevou em 1,61 kg, e o IMC reduziu em média 0,24 kg/m2, enquanto com o uso da sibutramina o peso reduziu em média 4,47 kg e o IMC reduziu em média 2,38 kg/m2 com p < 0,001.Conclusões : A sibutramina induziu significantemente mais perda de peso em adolescentes obesos em comparação ao placebo, sem efeitos colaterais significativos. A curva de evolução ponderal foi diferente de acordo com o momento em que a sibutramina foi introduzida. Esse achado indica que o melhor momento de introdução da sibutramina é quando a adesão começa a falhar. Arq Bras Endocrinol Metab. 2014;58(3):243-50

Objective : To evaluate the effect of sibutramine on weight loss in obese adolescents.Subjetcs and methods A double-blind controlled study lasting 13 months. The study included 73 obese adolescents of both sexes aged between 10 and 18 years. Laboratory tests and imaging studies were performed before, during wash-out, and at the end of 13 months.Results : The percentage of patients who lost 10% of their initial weight in the placebo group was 46%, and in the sibutramine group was 75%. When placebo was used, average weight rose by 1.61 kg, and BMI decreased by 0.24 kg/m2 whereas with the use of sibutramine, weight decreased by 4.47 kg, and average BMI decreased, 2.38 kg/m2, with p < 0.001.Conclusions : Sibutramine induced significantly more weight loss in obese adolescents compared with placebo, without significant side effects. The weight loss curve was different depending on the moment sibutramine was introduced. This finding indicates that the best time to start sibutramine is when adhesion begins to fail. Arq Bras Endocrinol Metab. 2014;58(3):243-50

Background: Carbohydrate counting (CHC) is acknowledged 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.

Antecedentes: El conteo de carbohidratos (CCH) es reconocido por la Asociación Americana de Diabetes (AAD) como una herramienta importante. Objetivo: Evaluar la eficacia de materiales educativos fotográficos en el entrenamiento de adolescentes con DM para realizar el CCH. Sujetos y Métodos: se distribuyó al azar a 76 adolescentes a dos grupos de orientación de CCH: mediante materiales fotográficos (Foto) o mediante listado de alimentos (Lista). Un mes después, se contactó a los participantes por teléfono para responder a preguntas sobre CCH para reforzar el entrenamiento (Encuesta). Dos días después de la encuesta, se pidió a los participantes que visitaran una cocina experimental para observar las porciones de los alimentos al natural y responder a un cuestionario sobre los pesos en gramos o equivalentes de carbohidratos de estas porciones. Se estableció la significación estadística en un valor de p < 0,05. Resultados: 54 adolescentes completaron el estudio (79,7 % mujeres), siendo el 51,8 % asignados al grupo Foto y el 48,1 % al grupo Lista. La edad promedio fue de 13,8 ± 2,0 años y el índice de masa corporal (IMC) promedio fue de 21,0 ± 3,2 kg/m². Los participantes tenían un promedio de 7,9 ± 1,5 años de escolarización, y sus padres 8,0 ± 3,8 años. EL conocimiento en el CCH fue similar en ambos grupos antes de la intervención. Después de la misma, el grupo Foto consiguió una diferencia significativa en la tasa de aciertos en el test de evaluación del CCH con respecto al grupo Lista (Foto: 2,5 frente a Lista: 1.0; p = 0,03). Conclusiones: el material educativo fotográfico fue más eficaz a la hora de ayudar a los adolescentes con DM a comprender y aprender a realizar el conteo de hidratos de carbono.

OBJETIVO: Avaliar a densidade mineral óssea (DMO) lombar em meninas com transtorno alimentar no diagnóstico e após seis meses e um ano de tratamento. SUJEITOS E MÉTODOS: Estudo prospectivo com 35 adolescentes do sexo feminino, portadoras de AN ou TANE acompanhadas por um ano. A densitometria óssea (DO) da coluna lombar L1-L4 pelo método de absorciometria com raios X de dupla energia (DXA) foi realizada no início, após seis meses e um ano de tratamento. RESULTADOS: Houve aumento do peso, da altura e do índice de massa corporal (IMC), progressão da idade óssea (p < 0,001), e 70% das adolescentes com amenorreia secundária restabeleceram os ciclos menstruais. No entanto, não houve diferença significativa do escore Z da DO lombar ao longo de um ano (p = 0,76). CONCLUSÃO: A recuperação da DMO não ocorre ao mesmo tempo em que a restauração do eixo hipotalâmico-hipofisário-gonadal.

OBJECTIVE: To evaluate lumbar bone mineral density (BMD) in girls with eating disorders in the beginning of the treatment, at six months, and after one year of treatment. SUBJECTS AND METHODS: This prospective study involved 35 female adolescents with AN or EDNOS treated during one year. Lumbar (L1-L4) bone mineral density by DXA was performed in the beginning of treatment, at six months, and after one year of treatment. RESULTS: There was improvement in weight, length, BMI, bone age (p < 0.001), and 70% of the adolescents with secondary amenorrhea had their menstrual cycles restored. However, the Z-score of lumbar BMD did not show differences during one year of follow-up (p = 0.76). CONCLUSION: The recovery of BMD does not occur together with the restoration of hypothalamic-pituitary-gonadal axis.

Relatamos um caso de hipoplasia adrenal congênita (HAC) e hipogonadismo hipogonadotrófico (HH) causado por uma nova mutação do gene DAX1. Paciente do sexo masculino com 19 meses de idade, hiperpigmentação e desenvolvimento inadequado foi encaminhado ao nosso serviço. Antecedente familiar de três irmãos falecidos por falência da adrenal, e um primo materno portador de insuficiência adrenal. Excluída a hipótese de adrenoleucodistrofia. A RM demonstrou hipófise e hipotálamo normais. Os níveis de hormônios plasmáticos mostraram alta concentração de ACTH (até 2.790 pg/mL) e baixos níveis de androstenediona, DHEA-S, 11-deoxicortisol e cortisol. Aos 14 anos de idade, o paciente ainda era pré-púbere, com peso de 43,6 kg (SDS: -0,87) e altura de 161 cm (SDS: -0,36), proporcionado. O teste do GnRH mostrou níveis basais e máximos de LH e FSH, respectivamente, iguais a 0,6/2,1 e < 1,0/< 1,0 U/L. A análise molecular identificou uma nova mutação que consiste da deleção do códon 372 (AAC; asparagina) no éxon 1 do gene DAX1. Essa mutação não foi encontrada em 200 alelos de indivíduos normais. A análise no site PredictProtein indicou que essa alteração, localizada no domínio de ligação do DAX1, pode danificar a proteína. Nossa hipótese é que essa nova mutação (p.Asp372del) do gene DAX1 pode levar a uma alteração na função da proteína DAX1 e está provavelmente envolvida no desenvolvimento da HAC e HH nesse paciente. Arq Bras Endocrinol Metab. 2012;56(8):496-500

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. Arq Bras Endocrinol Metab. 2012;56(8):496-500