Normal ambulatory blood pressure in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy

ABSTRACT Objective: Herein, we compared ambulatory blood pressure (ABP) between young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency and a control group. Additionally, we analyzed correlations between the glucocorticoid dose and androgen levels and ABP parameters. Subjects and methods: This case-control study included 18 patients (6 males and 12 females) and 19 controls (8 males and 11 females) matched by age (18-31 years). ABP monitoring was used to estimate blood pressure (BP) over a 24-h period. Results: No difference was noted between patients and controls in terms of systolic BP (males, 115.5 ± 5.6 vs. 117.0 ± 9.3, P = 0.733; and females, 106.4 ± 7.9 vs. 108.4 ± 7.6, P = 0.556, respectively) and diastolic BP during 24 h (males, 62.8 ± 7.5 vs. 66.2 ± 5.6, P = 0.349; and females, 62.7 ± 4.9 vs. 62.3 ± 4.9, P = 0.818, respectively). Systolic and diastolic BP and pulse pressure during daytime and nocturnal periods were similar between patients and controls. Furthermore, no differences were detected in the percentage of load and impaired nocturnal dipping of systolic and diastolic BP between patients and controls during the 24-h period. Additionally, the glucocorticoid dose (varying between r = −0.24 to 0.13, P > 0.05) and androgens levels (varying between r = 0.01 to 0.14, P > 0.05) were not associated with ABP parameters. Conclusion: No signs of an elevated risk for hypertension were observed based on ABP monitoring in young adults with CAH attributed to 21OHase deficiency undergoing glucocorticoid replacement therapy.

Bariatric surgery: is it reasonable before the age of 16? / Cirurgia bariátrica: é razoável antes dos 16 anos de idade?

ABSTRACT Objective: to assess the severity of obesity in children and adolescents through the presence of comorbidities and the potential indication of bariatric surgery. Methods: we conducted a cross-sectional study with clinical and laboratory data of the first consultation of patients at the childhood obesity clinic at a tertiary hospital from 2005 to 2013. We divided the patients into groups with or without potential indication for surgery, and recorded age, gender, birth weight, age of obesity onset, BMI Z score, presence of acanthosis nigricans, blood pressure, total cholesterol and fractions, triglycerides, blood glucose and fasting insulin, HOMA1-IR, CRP and ESR. The group with potential indication for surgery included: BMI > 40 or between 35-40 with comorbidities (Triglycerides >130mg/dl, glucose levels >100mg/dl, HOMA1-IR >3.16, Total Cholesterol >200mg/dl, LDL >130mg/dl and HDL <45mg/dl), regardless of age, epiphysis consolidation and previous treatment. Results: of the 296 patients included in the study, 282 (95.3%) were younger than 16 years. The most frequent change was the HDL (63.2%), followed by HOMA1-IR (37.5%). Of the group of 66 patients with potential indication for surgery (22.3%), only ten (15.1%) had more than 16 years. Acanthosis nigricans, the average HOMA1-IR, insulin, CRP, ESR, age, BMI Z score and systolic and diastolic blood pressure were significant in the group with potential surgical indication. Conclusion: bariatric surgery might be indicated by BMI and comorbidities in children and adolescents under 16 years.

RESUMO Objetivo: avaliar a gravidade da obesidade em crianças e adolescentes pela presença de comorbidades e pela potencial indicação de cirurgia bariátrica. Métodos: estudo transversal com dados clínicos e laboratoriais da primeira consulta de pacientes do ambulatório de obesidade infantil em um hospital terciário no período de 2005 a 2013. Os pacientes foram divididos em grupos com ou sem potencial indicação cirúrgica, e associados com idade, sexo, peso de nascimento, idade de início da obesidade, escore z de IMC, presença de acantose nigricans, pressão arterial, colesterol total e frações, triglicérides, glicemia e insulina de jejum, HOMA1-IR, PCR e VHS. O grupo com potencial indicação cirúrgica incluiu: IMC >40 ou IMC entre 35-40 com comorbidades (Triglicérides >130mg/dl, Glicemia >100mg/dl, HOMA1-IR >3,16, Colesterol total >200mg/dl, LDL >130mg/dl e HDL <45mg/dl), independente da idade, consolidação das epífises e tratamento prévio. Resultados: de 296 pacientes incluídos no estudo, 282 (95,3%) tinham menos de 16 anos. A alteração mais frequente foi a do HDL (63,2%), seguido do HOMA1-IR (37,5%). Do grupo de 66 pacientes com potencial indicação cirúrgica (22,3%), apenas dez (15,1%) tinham mais de 16 anos. Acantose nigricans, as médias de HOMA1-IR, insulina, PCR, VHS, idade, escore z de IMC e pressões sistólica e diastólica foram significantes no grupo com potencial indicação cirúrgica. Conclusão: os resultados sugerem que a cirurgia bariátrica, poderia estar indicada pelo IMC e presença de comorbidades, em crianças e adolescentes com menos de 16 anos.

Metabolic syndrome in obese adolescents: what is enough? / Síndrome metabólica em adolescentes obesos: o que é suficiente?

OBJECTIVE: To study the agreement among three distinct criteria for metabolic syndrome (MS) adapted to adolescents, and to identify associated factors for MS. METHODS: Cross-sectional study with 65 obese subjects aged 10 to 18 years, attended to at the Outpatient Clinic for Obese Children and Adolescents at the Clinical Hospital of the Universidade Estadual de Campinas (Unicamp). MS was defined using the criteria of the World Health Organization (WHO), the International Diabetes Federation (IDF), and the Adult Treatment Panel III (ATP III). Clinical, anthropometrical, and laboratorial data were associated to MS. RESULTS: From the 65 subjects, none had MS according to the WHO criteria, while 18 were diagnosed with MS (27.6%) according to the IDF, and 19 (29.2%) according to the ATP III. Agreement between IDF and ATP III was excellent (kappa 81%). In this study, puberty and triglycerides levels showed significant statistical difference when comparing subjects with and without MS, the first for ATP III (p = 0.03), and the second for IDF (p = 0.005) and ATP III (p = 0.001) criteria. CONCLUSION: The WHO criteria does not seem to be adequate for adolescents. IDF and ATP III criteria had an excellent agreement. Puberty and triglycerides were associated with MS.

OBJETIVO: Avaliar a correlação de três critérios de síndrome metabólica (SM) para adolescentes e identificar fatores associados. MÉTODOS: Estudo transversal com 65 pacientes obesos entre 10 e 18 anos do Ambulatório de Crianças e Adolescentes Obesos do HC-Unicamp. SM foi definida de acordo com a Organização Mundial da Saúde (OMS), International Diabetes Federation (IDF) e Adult Treatment Panel III (ATP III). Buscaram-se fatores associados a SM em dados clínicos, antropométricos e laboratoriais. RESULTADOS: Dos 65 pacientes, nenhum foi diagnosticado como SM pela OMS, sendo 18 (27.6%) pelo IDF e 19 (29.2%) pelo ATP III. A correlação entre IDF e ATP III foi excelente (kappa 81%). Neste estudo, a puberdade e os triglicérides apresentaram diferença estatisticamente significativa entre pacientes com e sem SM, sendo a primeira para o ATP III (p = 0.03) e o segundo para IDF (p = 0.005) e ATPIII (p = 0.001). CONCLUSÃO: O critério da OMS não parece ser adequado para adolescentes. Há correlação excelente entre os critérios do IDF e ATP III. Puberdade e triglicérides foram fatores associados à SM.

46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene / DDS 46,XX e síndrome de Antley-Bixler causada por novas mutações no gene da enzima P450 oxidorredutase

Deficiency of the enzyme P450 oxidoreductase is a rare form of congenital adrenal hyperplasia with characteristics of combined and partial impairments in steroidogenic enzyme activities, as P450 oxidoreductase transfers electrons to CYP21A2, CYP17A1, and CYP19A1. It results in disorders of sex development and skeletal malformations similar to Antley-Bixley syndrome. We report the case of a 9-year-old girl who was born with virilized genitalia (Prader stage V), absence of palpable gonads, 46,XX karyotype, and hypergonadotropic hypogonadism. During the first year of life, ovarian cyst, partial adrenal insufficiency, and osteoarticular changes, such as mild craniosynostosis, carpal and tarsal synostosis, and limited forearm pronosupination were observed. Her mother presented severe virilization during pregnancy. The molecular analysis of P450 oxidoreductase gene revealed compound heterozygosis for the nonsense p.Arg223*, and the novel missense p.Met408Lys, inherited from the father and the mother, respectively. Arq Bras Endocrinol Metab. 2012;56(8):578-85.

A deficiência da enzima P450 oxidorredutase é uma forma rara de hiperplasia congênita da adrenal com características de inibição combinada e parcial de enzimas esteroidogênicas, pois a enzima P450 oxidorredutase participa da transferência de elétrons para as enzimas CYP21A2, CYP17A1 e CYP19A1. Essa deficiência causa um distúrbio do desenvolvimento do sexo e alterações esqueléticas semelhantes às da síndrome de Antley-Bixley. Relatamos o caso de uma menina, atualmente com 9 anos de idade, que apresentava ao nascimento genitais virilizados (Prader 5) sem gônadas palpáveis, com cariótipo 46,XX e hipogonadismo hipergonadotrófico. No primeiro ano de vida, foram observados cisto ovariano, insuficiência adrenal parcial e alterações osteoarticulares como leve craniossinostose, sinostose carpal e tarsal e limitação de pronossupinação dos membros superiores. Sua mãe apresentou intensa virilização durante a gestação. O estudo molecular do gene P450 oxidorredutase revelou a heterozigose composta das mutações nonsense p.Arg223* e da missense nova p.Met408Lys, herdadas do pai e da mãe, respectivamente. Arq Bras Endocrinol Metab. 2012;56(8):578-85.