Spontaneous fertility and variable spectrum of reproductive phenotype in a family with adult-onset X-linked adrenal insufficiency harboring a novel DAX-1/NR0B1 mutation.

BACKGROUND: Adrenal hypoplasia congenita (AHC) is an X-linked disorder that affects the adrenal cortex and hypothalamus-pituitary-gonadal axis (HPG), leading to primary adrenocortical insufficiency (PAI) and hypogonadotropic hypogonadism. AHC is caused by a mutation in the DAX-1 gene (NR0B1). More commonly, this disease is characterized by early-onset PAI, with symptoms in the first months of life. However, a less severe phenotype termed late-onset AHC has been described, as PAI signs and symptoms may begin in adolescence and adulthood. Here we describe a family report of a novel mutation within NR0B1 gene and variable reproductive phenotypes, including spontaneous fertility, in a very late-onset X-linked AHC kindred. CASE PRESENTATION: Three affected maternal male relatives had confirmed PAI diagnosis between 30 y and at late 64 y. The X-linked pattern has made the endocrinology team to AHC suspicion. Regarding the HPG axis, all males presented a distinct degree of testosterone deficiency and fertility phenotypes, varying from a variable degree of hypogonadism, oligoasthenoteratozoospermia to spontaneous fertility. Interestingly, the other five maternal male relatives unexpectedly died during early adulthood, most likely due to undiagnosed PAI/adrenal crisis as the probable cause of their premature deaths. Sequencing analysis of the NR0B1 gene has shown a novel NR0B1 mutation (p.Tyr378Cys) that segregated in three AHC family members. CONCLUSIONS: NR0B1 p.Tyr378Cys segregates in an AHC family with a variable degree of adrenal and gonadal phenotypes, and its hemizygous trait explains the disease in affected family members. We recommend that NR0B1 mutation carriers, even those that are allegedly asymptomatic, be carefully monitored while reinforcing education to prevent PAI and consider early sperm banking when spermatogenesis still viable.

Abdominal circumference as an indicator of clinical and laboratory parameters associated with obesity in children and adolescents: comparison between two reference tables.

OBJECTIVE: To evaluate the sensitivity and specificity of two pediatric abdominal circumference reference tables to detect abnormally high body mass index, total cholesterol, fasting blood insulin and leptin levels, and homeostasis model assessment values. METHODS: A total of 624 male and female subjects, with ages ranging from 7 to 18 years, were evaluated. All children were recruited from two public schools. Venous blood samples were collected for determination of fasting plasma insulin, glucose, leptin, and total cholesterol levels. Weight, height and abdominal circumference were assessed according to internationally accepted guidelines. Contingency tables were constructed, comparing the presence or absence of increased abdominal circumference, according to cutoff points established by Taylor et al. and Freedman et al., with the presence or absence of abnormal values in the laboratory tests. RESULTS: Sensitivity values were consistently higher for the table by Taylor et al., whereas the table by Freedman et al. showed greater specificity. Positive predictive values were quite low in general, and were only relevant for body mass index. CONCLUSIONS: Results indicate that the table by Taylor et al. is best for screening purposes, as it identifies individuals at higher risk of presenting abnormal test results. On the other hand, the reference table by Freedman et al. is more suitable for clinical practice, as it could be used to replace laboratory measurements, such as blood insulin or leptin levels, which may not be available at all sites.

Circunferência abdominal como indicador de parâmetros clínicos e laboratoriais ligados à obesidade infanto-juvenil: comparação entre duas referências / Abdominal circumference as an indicator of clinical and laboratory parameters associated with obesity in children and adolescents: comparison between two reference tables

OBJETIVO: Avaliar sensibilidade e especificidade de duas tabelas de referência para circunferência abdominal em crianças na detecção de valores elevados de índice de massa corporal, colesterol total, insulinemia de jejum, leptinemia de jejum e homeostasis model assessment. MÉTODOS: Foram avaliados 624 indivíduos, de ambos os sexos, com idades entre 7 e 18 anos, provenientes de duas escolas públicas, obtendo-se amostra de sangue venoso em jejum para dosagens de insulina, glicemia, leptina e colesterol total. Peso, estatura e circunferência abdominal foram aferidos de acordo com recomendações internacionais. Foram montadas tabelas de contingência em que se compararam, de um lado, a presença ou ausência de aumento na circunferência abdominal segundo os pontos de corte propostos de Taylor et al. e Freedman et al. e, de outro, presença ou ausência de valores alterados dos parâmetros avaliados. RESULTADOS: Os valores de sensibilidade foram sempre superiores para a tabela de Taylor et al., ao contrário da especificidade, sempre mais elevada para a tabela de Freedman et al. Os valores preditivos positivos foram, em geral, bastante baixos, mostrando-se relevantes apenas para o indicador índice de massa corpórea. CONCLUSÕES: Os resultados obtidos apontam para que se considere a referência de Taylor et al. melhor do ponto de vista da triagem, selecionando indivíduos com maior probabilidade de apresentarem as alterações estudadas; por outro lado, a referência de Freedman et al. mostrou-se mais adequada para uso clínico, sendo possível a sua utilização para substituir dosagens que possam não estar ao alcance do profissional, como insulinemia e leptinemia.

OBJECTIVE: To evaluate the sensitivity and specificity of two pediatric abdominal circumference reference tables to detect abnormally high body mass index, total cholesterol, fasting blood insulin and leptin levels, and homeostasis model assessment values. METHODS: A total of 624 male and female subjects, with ages ranging from 7 to 18 years, were evaluated. All children were recruited from two public schools. Venous blood samples were collected for determination of fasting plasma insulin, glucose, leptin, and total cholesterol levels. Weight, height and abdominal circumference were assessed according to internationally accepted guidelines. Contingency tables were constructed, comparing the presence or absence of increased abdominal circumference, according to cutoff points established by Taylor et al. and Freedman et al., with the presence or absence of abnormal values in the laboratory tests. RESULTS: Sensitivity values were consistently higher for the table by Taylor et al., whereas the table by Freedman et al. showed greater specificity. Positive predictive values were quite low in general, and were only relevant for body mass index. CONCLUSIONS: Results indicate that the table by Taylor et al. is best for screening purposes, as it identifies individuals at higher risk of presenting abnormal test results. On the other hand, the reference table by Freedman et al. is more suitable for clinical practice, as it could be used to replace laboratory measurements, such as blood insulin or leptin levels, which may not be available at all sites.