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.

Adrenal insufficiency in association with congenital nephrotic syndrome: a case report.

Adrenal disorders in patients with congenital nephrotic syndrome (CNS) have seldom been reported, and the mechanisms that could explain this association are not known. The follow-up of a male infant diagnosed with CNS and primary adrenal insufficiency in his first year of life is the object of this paper.

Neonatal screening for congenital adrenal hyperplasia.

OBJECTIVE: The effectiveness of neonatal screening for reducing morbimortality in children with congenital adrenal hyperplasia (CAH) is the main justification for its implementation. One of the challenges for its implementation is to determine the cutoff value for laboratory measurement of 17-hydroxyprogesterone (17OHP) with appropriate cost-effectiveness. This study identified factors affecting the results of the pilot project of newborn screening for CAH, performed in the state of Minas Gerais, Brazil. METHODS: Neonatal screening performed between September, 2007 and May, 2008, with 17OHP measurements performed in blood samples taken from the heel (filter paper), on the 5(th) day of life, processed by the UMELISA 17-OH Progesterona NEONATAL(®) method. The cutoff value was 80 and 160 nmol/L for healthy children or not, respectively. RESULTS: The incidence of CAH was 1:19,939 in 159,415 children screened. The 99(th) percentile (p99) of 17OHP in the first sample was 108 nmol/L. In 13,298 newborns whose weight had been reported, the p99 of 17OHP were, respectively: 344 nmol/L for weight < 1,500 g; 260 nmol/L for weight between 1,500 and 1,999 g; 221 nmol/L for weight between 2,000 and 2,499 g; 109 nmol/L for weight ≥ 2,500g. The rate of recall for medical consultation was 0.31%. The test sensitivity was 100%, specificity was 99.6%, and the positive predictive value was 2.2%. By adjusting the cutoff values of 17OHP to 110 nmol/L and 220 nmol/L, a 76% decrease in consultation referrals was projected. CONCLUSION: The use of 17OHP cutoff values, considering birth weight, was a cost-effective measure to reduce false positives. The results of this pilot study suggest that screening for CAH might benefit the pediatric population.

Triagem neonatal para hiperplasia adrenal congênita / Neonatal screening for congenital adrenal hyperplasia

OBJETIVO: A eficácia da triagem neonatal para redução de morbimortalidade das crianças com hiperplasia adrenal congênita (HAC) é a principal justificativa para sua implantação. Um dos desafios para sua realização é a determinação do ponto de corte para a medida laboratorial da 17-hidroxiprogesterona (17OHP) que apresente adequado custo/benefício. Neste estudo foram identificados fatores intervenientes nos resultados do projeto-piloto de triagem neonatal para HAC, realizado em Minas Gerais. MÉTODOS: Rastreamento neonatal entre 09/2007 e 05/2008, com dosagens da 17OHP de amostras de sangue colhidas no calcanhar, no 5º dia de vida (papel-filtro), processadas pelo método UMELISA 17-OH Progesterona NEONATAL®. Os pontos de corte foram 80 e 160 nmol/L, para crianças saudáveis ou não, respectivamente. RESULTADOS: A incidência de HAC foi 1:19.939 em 159.415 crianças triadas. O percentil 99 (p99) da 17OHP, na primeira amostra, foi 108 nmol/L. Em 13.298 recém-nascidos com peso informado, os p99 da 17OHP foram, respectivamente, 344 nmol/L para <1500 g, 260 nmol/L para 1500 a 1999 g, 221 nmol/L para 2000 a 2499 g, e 109 nmol/L para > 2500 g. A taxa de reconvocação para consulta médica foi 0,31%. A sensibilidade do teste foi 100%, a especificidade, 99,6% e o valor preditivo positivo, 2,2%. Ajustando-se o ponto de corte da 17OHP para 110 nmol/L e 220 nmol/L, projetou-se redução em 76% dos encaminhamentos para consulta. CONCLUSÃO: Adoção dos pontos de corte para 17OHP, considerando peso de nascimento, apresentou-se como medida custo-efetiva para redução de falso-positivos. Os resultados desse estudo piloto sugerem que a triagem para HAC possa beneficiar a população infantil.

OBJECTIVE: The effectiveness of neonatal screening for reducing morbimortality in children with congenital adrenal hyperplasia (CAH) is the main justification for its implementation. One of the challenges for its implementation is to determine the cutoff value for laboratory measurement of 17-hydroxyprogesterone (17OHP) with appropriate cost-effectiveness. This study identified factors affecting the results of the pilot project of newborn screening for CAH, performed in the state of Minas Gerais, Brazil. METHODS: Neonatal screening performed between September, 2007 and May, 2008, with 17OHP measurements performed in blood samples taken from the heel (filter paper), on the 5th day of life, processed by the UMELISA 17-OH Progesterona NEONATAL® method. The cutoff value was 80 and 160 nmol/L for healthy children or not, respectively. RESULTS: The incidence of CAH was 1:19,939 in 159,415 children screened. The 99th percentile (p99) of 17OHP in the first sample was 108 nmol/L. In 13,298 newborns whose weight had been reported, the p99 of 17OHP were, respectively: 344 nmol/L for weight < 1,500 g; 260 nmol/L for weight between 1,500 and 1,999 g; 221 nmol/L for weight between 2,000 and 2,499 g; 109 nmol/L for weight > 2,500g. The rate of recall for medical consultation was 0.31%. The test sensitivity was 100%, specificity was 99.6%, and the positive predictive value was 2.2%. By adjusting the cutoff values of 17OHP to 110 nmol/L and 220 nmol/L, a 76% decrease in consultation referrals was projected. CONCLUSION: The use of 17OHP cutoff values, considering birth weight, was a cost-effective measure to reduce false positives. The results of this pilot study suggest that screening for CAH might benefit the pediatric population.

Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita.

OBJECTIVE: To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. CASE REPORT: We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. RESULTS: DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. CONCLUSION: A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease.

Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita / Identificação de nova mutação no gene DAX1/NR0B1A em dois irmãos com forma clínica grave de hipoplasia adrenal congênita

OBJECTIVE: To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. CASE REPORT: We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. RESULTS: DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. CONCLUSION: A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease.

OBJETIVO: Pesquisar mutações no gene DAX1/NR0B1A em dois irmãos com suspeita de hipoplasia adrenal congênita (HAC), rara doença potencialmente fatal, para estabelecer sua etiologia molecular. RELATO DOS CASOS: São apresentados os relatos de dois irmãos com síndrome perdedora de sal no período neonatal que receberam terapia de reposição hormonal para insuficiência adrenal primária. O diagnóstico de HAC foi suspeitado porque as crianças mantiveram, durante o tratamento hormonal, níveis plasmáticos reduzidos de 17-OH-progesterona e andrógenos ao lado de níveis elevados de ACTH. RESULTADOS: A análise molecular do gene DAX1 mostrou a mutação, confirmando o diagnóstico nos irmãos e o estado heterozigoto da mãe. No sequenciamento direto do DAX1 foi encontrada inserção de uma adenina (c1382-1383 A ins), levando à substituição pMet461Asp. CONCLUSÃO: Uma nova mutação da fase de leitura no gene DAX1 foi identificada, estabelecendo a etiologia molecular da HAC nos dois irmãos. Um diagnóstico genético preciso deste distúrbio adrenal, frequentemente não confirmado apenas pelos aspectos clínicos, pode ter importantes implicações para o manuseio em longo prazo da doença.

Predictive factors of ultrasonographic involution of prenatally detected multicystic dysplastic kidney.

OBJECTIVE: To evaluate possible predictive factors of involution on ultrasonography (US) or disappearance of a prenatally detected multicystic dysplastic kidney (MCDK). PATIENTS AND METHODS: Forty-five children with unilateral MCDK detected by prenatal ultrasonography between 1989 and 2002 were analysed. All patients except one had (99m)Tc isotopic scintigraphy to confirm the absence of renal function in the MCDK. All children were managed conservatively with follow-up visits every 6 months, with US 6-monthly during the first 2 years of life and yearly thereafter. Survival was analysed using the Kaplan-Meier method to evaluate the involution of the MCDK, with differences between subgroups assessed using the two-sided log-rank test. Cox's regression model was applied for the multivariate analysis. RESULTS: The mean (range) follow-up was 50 (12-167) months; in all, 279 ultrasonograms were taken, the mean (range) number per patient being 6 (3-10). US showed partial involution of the MCDK in 30 (67%) cases and complete involution in nine (20%). The absolute MCDK length remained almost unchanged in six children (13%). Univariate analysis showed that four variables were possibly associated with complete involution of the MCDK (gender, impalpable kidney, renal length at admission using two thresholds, 62 and 78 mm). After adjusting by Cox's model only a renal length at diagnosis of <62 mm remained associated with complete involution (relative risk 8, 95% confidence interval 0.98-68; P = 0.05). CONCLUSION: These results suggest that only a renal length of <62 mm on initial US was predictive of complete involution of the MCDK during the follow-up.

Natural history of multicystic kidney conservatively managed: a prospective study.

We report the long-term clinical results of conservative management of children with unilateral multicystic dysplastic kidneys (MCDK). Between 1989 and 2002, 43 children with MCDK detected by prenatal ultrasonography were prospectively followed. At birth, ultrasonography confirmed the prenatal findings in all cases. Patients underwent a radioisotope scan and micturating cystogram in order to confirm the diagnosis and to exclude other uropathies. Follow-up ultrasound (US) examinations were performed at 6-month intervals during the first 2 years of life and yearly thereafter. The mean follow-up time was 42 months (range 12-156 months). Two children developed hypertension during follow-up. In total 257 US scans were performed. The mean number of US scans per patient was 6 (range 3-10). US scans demonstrated partial involution of the MCDK in 30 (70%) cases and complete involution in 8 (19%). The absolute MCDK length remained almost unchanged in 5 children (11%). The estimated median time of complete involution of the MCDK was 122 months [95% confidence interval (CI)=86-158 months]. A total of 33 (76.7%) contralateral kidneys underwent compensatory hypertrophy, reaching a renal length above the 95th percentile during follow-up. The estimated median time for the occurrence of compensatory hypertrophy was 30 months (95% CI=15-45 months). In conclusion, the natural history of MCDK is usually benign but patients must have long-term follow-up with US scans and blood pressure measurements.

Abordagem pós-natal das anomalias do trato urinário diagnosticadas intra-útero pela ultra-sonografia: [revisão] / Posnatal approach of the urinary tract anomalies identified in prenatal diagnosis by ultra-sonography: [review]

Os avanços no diagnóstico pré-natal nas últimas duas décadas têm permitido um aperfeiçoamento no manejo das anomalias do trato urinário de estudo observacionais tem demonstrado que o manejo conservador, isto é, sem intervenção cirúrgica, é seguro e permite a preservação da função renal na maioria das anomalias do trato urinário identificadas no pré-natal. Uma abordagem adequada dos neonatos portadores de malformações do trato urinário depende da atuação conjunta de uma equipe multidisciplinar, incluindo medicinal fetal, neonatologia, radiologia, nefrologia, urologia e cirurgia pediátrica. Deve ser uma abordagem sistemática, evitando-se negligenciar possíveis graves uropatias e, ao mesmo tempo, prevenindo a realização de uma propedêutica invasiva e de alto custo, as vezes desnecessária.

The advances of prenatal diagnosis in the last two decades have allowed an improvement in the management of the urinary tract anomalies. The early diagnosis, before any clinical manifestation, has contributed to a better understanding of the natural history of the uropathies and has allowed a more conservative management, except for the cases of posterior urethral valves. Series of observational studies have demonstrated that the conservative approach, that is, the one without surgical intervention, is safe and allows the preservation of the renal function in most of the prenatally identified urinary tract anomalies. The best postnatal care of newborn carriers of urinary tract malformations depends on an integrated performance of a multidisciplinar team, including fetal medicine, neonatology, radiology, nephrology, urology and pediatric surgery. There should be a systematic approach, avoiding neglecting possible serious uropathies and, at the sametime, preventing the accomplishment of invasive and ligh cost diagnosis tests when they are unnecessary.