Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension.

OBJECTIVE: To identify novel biomarkers associated with pediatric primary hypertension. METHODS: We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded. RESULTS: In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P < 0.001), HOMA-IR (r = 0.211, P < 0.001), MMP-9 activity (r = 0.215, P < 0.001) and the cortisol/cortisone ratio (r = 0.231, P < 0.001). DBP showed similar correlations with these variables. No correlation was observed with aldosterone or plasma renin activity. Participants were categorized as hypertensive (n = 59) or nonhypertensive (n = 261). In the univariate analysis, hypertensive patients had higher BMI-SDS (P < 0.001), HOMA-IR (P < 0.001), high-sensitivity C-reactive protein (P < 0.001), MMP-9 activity (P < 0.001), plasminogen activator inhibitor type 1 (P < 0.001) and cortisol/cortisone ratio (P < 0.001) than nonhypertensive patients. Multiple regression analysis showed that the variables that remained associated with hypertension were higher BMI-SDS [odds ratio (OR) = 3.74; 95% confidence interval (CI) = 1.84-7.58], a higher cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32). CONCLUSION: We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.

Usefulness and Pitfalls in Sodium Intake Estimation: Comparison of Dietary Assessment and Urinary Excretion in Chilean Children and Adults.

BACKGROUND: High sodium intake has been associated with various noncommunicable disease like hypertension, cardiovascular disease, or stroke. To estimate accurately sodium intake is challenging in clinical practice. We investigate the usefulness and limitations of assessing sodium intake simultaneously by dietary assessment and urinary samples in both children and adults. METHODS: We used a cross-sectional study design inviting 298 Chilean subjects (74 children and 222 adults) aged between 9 and 66 years of both genders. Sodium intake by dietary assessment was obtained from Chilean food composition data, based on FAO tables. Sodium and creatinine excretion were measured in 24-hour urine samples, in all participants. RESULTS: Adequate urinary collection was obtained in 81% of children (59/74) and 61% of adults (135/222). The mean sodium intake by dietary assessment was similar to the sodium excretion in 24 hours (3,121±1,153mg/d vs. 3,114±1,353mg/24h, P = nonsignificant) in children but was significantly lower (3,208±1,284mg/d vs. 4,160±1,651mg/24h, P < 0.001) in adults. In both children and adults, sodium intake correlated with urinary sodium excretion (r = 0.456, P < 0.003 and r = 0.390, P < 0.001, respectively). Secondary analyses also suggested that the dietary assessment was more inaccurate in overweight adult subjects. CONCLUSIONS: Our results showed that average sodium intake was higher than recommended in both children and adults (WHO ≤2,000mg/d). The sodium intake estimated by dietary assessment correlated with urinary excretion in all subjects, but in obese adults was more inaccurate than in children. Future studies to validate the appropriate test to assess sodium intake by age and nutritional status are warranted.

Transcription factor 7-like 1 is involved in hypothalamo-pituitary axis development in mice and humans.

Aberrant embryonic development of the hypothalamus and/or pituitary gland in humans results in congenital hypopituitarism (CH). Transcription factor 7-like 1 (TCF7L1), an important regulator of the WNT/ß-catenin signaling pathway, is expressed in the developing forebrain and pituitary gland, but its role during hypothalamo-pituitary (HP) axis formation or involvement in human CH remains elusive. Using a conditional genetic approach in the mouse, we first demonstrate that TCF7L1 is required in the prospective hypothalamus to maintain normal expression of the hypothalamic signals involved in the induction and subsequent expansion of Rathke's pouch progenitors. Next, we reveal that the function of TCF7L1 during HP axis development depends exclusively on the repressing activity of TCF7L1 and does not require its interaction with ß-catenin. Finally, we report the identification of two independent missense variants in human TCF7L1, p.R92P and p.R400Q, in a cohort of patients with forebrain and/or pituitary defects. We demonstrate that these variants exhibit reduced repressing activity in vitro and in vivo relative to wild-type TCF7L1. Together, our data provide support for a conserved molecular function of TCF7L1 as a transcriptional repressor during HP axis development in mammals and identify variants in this transcription factor that are likely to contribute to the etiology of CH.

Metabolic syndrome and its components are strongly associated with an inflammatory state and insulin resistance in the pediatric population / Síndrome metabólico y sus componentes se asocian con insulino resistencia y marcadores de inflamación en poblacion pediátrica

Introduction: Endothelial inflammation and insulin resistance (IR) begin in childhood and constitute the pathophysiological basis of Metabolic Syndrome (MS). The increase levels in plasma of inflammatory markers such as high sensitive PCR (hsPCR), plasminogen activator inhibitor 1 (PAI-1) and tests suggestive of IR such as Insulin (Ins) and alanine aminotransferase (ALT) have been associated with MS in adults, but have not been studied in children. Objectives: Correlate the presence of MS and its components with the inflammatory and IR markers seen in the pediatric population. Methods: Cross-sectional study of 337 children (10,9±9,7 years) whose levels of hsPCR, PAI-1, Ins and ALT were determined, along with their association with MS and its individual components. Results: 37 children had MS (10,4%). The frequency of MS components was: abdominal obesity 38,5%, hypertension (HTN) 21,3%, hypertriglyceridemia 17,8%, HDL 21,3% and hyperglycemia 1,4%. hsPCR, PAI-1, ALT and Ins were higher in the presence of MS and increased progressively when components were came together. Conclusions: The pediatric population segment with MS had a higher concentration of hsPCR, PAI-1, Ins and ALT.These levels increase proportionally MS components add up, suggesting that even before diagnosis criteria are fulfilled there is a inflammatory state (AU)

Introducción: La insulino resistencia (IR) y la inflamación endotelial constituyen la base fisiopatológica del Síndrome metabólico (SM) . El aumento de los niveles plasmáticos de mascadores de inflamación como PCRus, Inhibidor del activador de plasminógeni tipo 1 (PAI-1) y parámetros sugerentes de insulino resistencia (IR) como insulina, triglicéridos y Alanino aminotransferasa (ALT) se han asociado a síndrome metabólico en adultos pero han sido menos estudiados en pediatría. . Objetivo: Correlacionar los componentes del SM con marcadores de inflamación e IR en población pediátrica. Métodos: Estudio transversal de 337 niños (10,9±9,7 años). Se determinó niveles plasmáticos de PCRus, PAI- 1, ALT e Insulina y se evaluó su asociación con Síndrome metabólico y sus criterios de forma individual. Resultados: 37 sujetos tuvieron diagnóstico de SM (10.4%). 38.5% presentó obesidad abdominal, 21.3% Hipertensión arterial, 17.8% Hipertrigliceridemia, 21.3% niveles bajos de HDL y un 1.4% Hiperglicemia. Encontramos que PCRus, PAI-1 y ALT fueron más altas en presencia de SM y aumentaban progresivamente a medida que se agregaban criterios diagnósticos. Conclusión: Este estudio demuestra que en población pediátrica con diagnóstico de SM existen niveles más altos de PCRus, PAI-1, ALT e insulina y que a mayor nú- mero de criterios presentes la inflamación pareciera ser mayor lo que sugiere que incluso antes de tener el diagnóstico de SM ya existe un estado pro inflamatorio (AU)

Metabolic syndrome and its components are strongly associated with an inflammatory state and insulin resistance in the pediatric population.

INTRODUCTION: Endothelial inflammation and insulin resistance (IR) begin in childhood and constitute the pathophysiological basis of Metabolic Syndrome (MS). The increase levels in plasma of inflammatory markers such as high sensitive PCR (hsPCR), plasminogen activator inhibitor 1 (PAI-1) and tests suggestive of IR such as Insulin (Ins) and alanine aminotransferase (ALT) have been associated with MS in adults, but have not been studied in children. OBJECTIVES: Correlate the presence of MS and its components with the inflammatory and IR markers seen in the pediatric population. METHODS: Cross-sectional study of 337 children (10,9±9,7 years) whose levels of hsPCR, PAI-1, Ins and ALT were determined, along with their association with MS and its individual components. RESULTS: 37 children had MS (10,4%). The frequency of MS components was: abdominal obesity 38,5%, hypertension (HTN) 21,3%, hypertriglyceridemia 17,8%, HDL 21,3% and hyperglycemia 1,4%. hsPCR, PAI-1, ALT and Ins were higher in the presence of MS and increased progressively when components were came together. CONCLUSIONS: The pediatric population segment with MS had a higher concentration of hsPCR, PAI-1, Ins and ALT.These levels increase proportionally MS components add up, suggesting that even before diagnosis criteria are fulfilled there is a inflammatory state.

La insulino resistencia (IR) y la inflamación endotelial constituyen la base fisiopatológica del Síndrome metabólico (SM) . El aumento de los niveles plasmáticos de mascadores de inflamación como PCRus, Inhibidor del activador de plasminógeni tipo 1 (PAI-1) y parámetros sugerentes de insulino resistencia (IR) como insulina, triglicéridos y Alanino aminotransferasa (ALT) se han asociado a síndrome metabólico en adultos pero han sido menos estudiados en pediatría. Objetivo: Correlacionar los componentes del SM con marcadores de inflamación e IR en población pediátrica. Métodos: Estudio transversal de 337 niños (10,9±9,7 años). Se determinó niveles plasmáticos de PCRus, PAI-1, ALT e Insulina y se evaluó su asociación con Síndrome metabólico y sus criterios de forma individual. Resultados: 37 sujetos tuvieron diagnóstico de SM (10.4%). 38.5% presentó obesidad abdominal, 21.3% Hipertensión arterial, 17.8% Hipertrigliceridemia, 21.3% niveles bajos de HDL y un 1.4% Hiperglicemia. Encontramos que PCRus, PAI-1 y ALT fueron más altas en presencia de SM y aumentaban progresivamente a medida que se agregaban criterios diagnósticos. Conclusión: Este estudio demuestra que en población pediátrica con diagnóstico de SM existen niveles más altos de PCRus, PAI-1, ALT e insulina y que a mayor número de criterios presentes la inflamación pareciera ser mayor lo que sugiere que incluso antes de tener el diagnóstico de SM ya existe un estado pro inflamatorio.

The Expression of RAC1 and Mineralocorticoid Pathway-Dependent Genes are Associated With Different Responses to Salt Intake.

BACKGROUND: Rac1 upregulation has been implicated in salt-sensitive hypertension as a modulator of mineralocorticoid receptor (MR) activity. Rac1 could affect the expression of oxidative stress markers, such as hemoxigenase-1 (HO-1) or nuclear factor-B (NF-κB), and the expression of neutrophil gelatinase-associated lipocalin (NGAL), a cytokine upregulated upon MR activation. AIM: We evaluated RAC1 expression in relation of high salt intake and association with MR, NGAL, HO-1, and NF-κB expression, mineralo- and glucocorticoids levels, and inflammatory parameters. SUBJECTS AND METHODS: We studied 147 adult subjects. A food survey identified the dietary sodium (Na) intake. RAC1 expression was considered high or low according to the value found in normotensive subjects with low salt intake. We determined the gene expression of RAC1, MR, NGAL, HO-1, NF-κB, and 18S, isolated from peripheral leukocytes. We measured aldosterone, cortisol, sodium, potassium excretion, metalloproteinase (MMP9 y MMP2), and C-reactive protein. RESULTS: We identified 126 subjects with high Na-intake, 18 subjects had high, and 108 low-RAC1 expression. The subjects with high-RAC1 expression showed a significant increase in MR (P = 0.0002), NGAL (P < 0.0001) HO-1 (P = 0.0004), and NF-κB (P < 0.0001) gene expression. We demonstrated an association between RAC1 expression and MR (R sp 0.64; P < 0.0001), NGAL (R sp 0.48; P < 0.0001), HO-1 (R sp 0.53; P < 0.0001), and NF-κB (R sp0.52; P < 0.0001). We did not identify any association between RAC1 and clinical or biochemical variables. CONCLUSIONS: RAC1 expression was associated with an increase in MR, NGAL, NF-κB, and HO-1 expression, suggesting that RAC1 could be a mediator of cardiovascular damage induced by sodium, and may also useful to identify subjects with different responses to salt intake.

[Waist-to-height ratio does not change with gender, age and pubertal stage in elementary school children]. / La razón cintura estatura en escolares no varía con el género, la edad ni la maduración puberal.

BACKGROUND: Waist-to-height ratio (WHtR) is a cardiometabolic risk indicator in children. A value greater than or equal to 0.55 is an effective screening tool for identifying obese children with metabolic syndrome. However, it is unclear whether this cutoff can be applied equally to any age or gender. AIM: To analyze the variability of WHtR by age, gender and pubertal stage in elementary school children. PATIENTS AND METHODS: Cross-sectional study in 2,980 school children (6-14 years old, 51% male) of Santiago, Chile. We measured weight, height and waist circumference and calculated body mass index and WHtR. Pubertal stage was assessed and classified as peripubertal (Tanner I and II) and pubertal (Tanner III, IV and V). RESULTS: The mean age was 9.9 ± 2.3 years, with no gender difference (p = 0.5). Eighty one percent of boys and 59.4% of girls were peripubertal (p < 0.001). The association between age-adjusted WHtR by gender and pubertal stage was not significant (p = 0.409). Therefore mean, standard deviation and percentiles of WHtR were calculated without sex and pubertal stage segmentations. CONCLUSIONS: Since WHtR does not vary with age, gender and pubertal status in elementary school children, it is possible to use a single cutoff value, previously defined in this population, to identify children with cardiometabolic risk.

Diagnosis and evaluation of hypogonadism.

Hypogonadism is defined as defects in gonadal response to gonadotropins or sex hormone biosynthesis. Clinical evaluation and diagnosis of patients is challenging, particularly before puberty. Basal determinations of the gonadotropins luteinizing hormone, follicle-stimulating hormone, the gonadal sex steroids testosterone and/or estrogen and markers of gonadal function including inhibin B and anti-Müllerian hormone are useful, but only at specific ages, thus necessitating combined hormonal tests with meticulous physical examination. GnRH testing can be useful, and may be used in combination with hCG testing to discriminate between isolated hypogonadotropic hypogonadism and constitutional delay of growth and puberty. Urine steroid profiles may be helpful in the diagnosis of androgen biosynthetic defects. Also increasingly important is genotypic screening for genetic or chromosomal abnormalities, together with detailed family and medical histories including antecedent substance abuse, chronic disease, and exposure to chemotherapy or radiotherapy. This chapter explores the diagnosis and evaluation of patients with hypogonadism and reviews the genetic/chromosomal factors involved in the condition.

Positive association between aldosterone-renin ratio and carotid intima-media thickness in hypertensive children.

INTRODUCTION: From an early age, hypertension can damage blood vessels through multiple mechanisms. The aim of this study was to evaluate the presence of vascular damage and whether it is associated with the mineralo- and glucocorticoid profiles of hypertensive children. SUBJECTS AND METHODS: We studied 64 hypertensive children. Anthropometric parameters and serum aldosterone (SA), plasma renin activity (PRA), aldosterone/renin ratio (ARR), cortisol (F) and cortisone (E) were measured. The serum F/E ratio was calculated to estimate the activity of the enzyme 11ß-HSD2. Vascular damage was determined by carotid intima-media thickness (cIMT) and flow-mediated dilation of the brachial artery (FMD) on ultrasound. RESULTS: (median; Q1-Q3) Of the patients observed, 39% were females, and the median value for age (years) was 11.2 (9.1-13.3), for BMI (SDS) was 1.36 (0.84-1.80), for body fat mass (%) was 28.3 (17.8-36.0), for SBP index was 1.17 (1.12-1.25) and for the DBP index was 1.27 (1.16-1.36). Measurements revealed an SA level higher than 491 pmol/l in 4/64 patients, a PRA value lower than 0.5 ng/ml/h in 2/64, an ARR higher than 10 in 3/64 and serum F/E ratio higher than 4.3 in 10/64. The median brachial FMD (%) was 8.41 (5.61-10.91), and the median cIMT (mm) was 0.40 (0.37-0.43). The ARR was the only variable that explained changes in cIMT (ß = 0.571, R(2 ) = 0.315, P < 0.0001). CONCLUSION: Our results showed a positive association between cIMT and the ARR, suggesting an important role of the renin-aldosterone axis in the regulation of early vascular damage in hypertensive children.

Pituitary gland development: an update.

The embryonic development of the pituitary gland involves a complex and highly spatio-temporally regulated network of integrating signalling molecules and transcription factors. Genetic mutations in any of these factors can lead to congenital hypopituitarism in association with a wide spectrum of craniofacial/midline defects ranging from incompatibility with life to holoprosencephaly (HPE) and cleft palate and septo-optic dysplasia (SOD). Increasing evidence supports a genotypic overlap with hypogonadotrophic hypogonadal disorders such as Kallmann syndrome, which is consistent with the known overlap in phenotypes between these disorders. This chapter reviews the cascade of events leading up to the successful development of the pituitary gland and to highlight key areas where genetic variations can occur thus leading to congenital hypopituitarism and associated defects.

Marcadores de síndrome metabólico como predictores de elevación de alanino aminotransferasa en niños / Association of metabolic syndrome markers with abnormal alanine aminotransferase levels in healthy children

Background: There is a high prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) among pediatric patients. The identification of clinical predictors of these conditions would allow a timely treatment. Aim: To evaluate the relationship between serum alanine aminotransferase levels and parameters of metabolic syndrome in asymptomatic school students without hepatic illness. Subjects and Methods: A randomized sample of 175 children aged between 9 and 14 years (54% females) was selected, from a database of 3010 students living in Santiago, Chile. Weight, height, abdominal circumference, systolic and diastolic blood pressure were measured. A fasting blood sample was obtained to measure glucose, total cholesterol, HDL, LDL-cholesterol, triglycerides, alanine aminotransferase (ALT) and insulin levels. Results: Forty percent of participants were obese, 17% had metabolic syndrome and 13.1% had abnormal ALT levels. Compared with children with normal ALT levels, the latter had significantly higher waist obesity, body mass index, systolic and diastolic blood pressure and triglycerides. However on multiva-riate analysis, only waist obesity was independently associated with abnormal ALT levels (adjusted odds ratio 3.93, 95% confidence intervals 1.44-10.78, p = 0.008). Conclusions: Only waist obesity was independently associated with abnormal ALT levels in this sample of children.

Prevalence of components of the metabolic syndrome according to birthweight among overweight and obese children and adolescents.

BACKGROUND/OBJECTIVES: Extremes of birthweight (BW) have been associated with increased rates of metabolic risks. The objective was to study the prevalence of metabolic risks markers among obese and overweight (OW) subjects according to BW. SUBJECTS/METHODS: A cross-sectional study was performed in a cohort of 1002 patients (2-18 years, 40.6% male) evaluated for OW or obese subjects in two private clinics. Anthropometrics, fasting lipids, glycemia, and insulin were obtained. RESULTS: Of the subjects, 76.1% were born appropriate for gestational age (AGA), 10.9% small for gestational age (SGA), and 13% large for gestational age (LGA). Children born LGA presented a more severe degree of obesity compared with those born AGA and SGA (p<0.0001). No differences in glycemia, insulin, and lipid levels were detected among the groups. Abnormal glucose was found in 37 subjects: one with type 2 diabetes mellitus (from the previously glucose-intolerant subjects), 10 with glucose intolerance, and 27 with impaired fasting glucose. According to Boney criteria, 6.6% of the patients (6-18 years old) exhibited metabolic syndrome (MS) (69.4% AGA, 12.9% SGA, and 17.7% LGA). CONCLUSIONS: Being born LGA represents a higher risk of severe obesity. At this age, the most frequent component of MS was an abnormal lipid profile with low high-density lipoprotein and high triglycerides. Finally, the most frequent finding associated with abnormalities of glucose tolerance was a family history of diabetes. Thus, BW, lipid profile, and family history are mandatory when these patients are evaluated.

Waist circumference percentiles in children and adolescents between 6 and 14 years from Santiago, Chile.

OBJECTIVE: To describe the percentile distribution of waist circumference (WC) by sex and age in a representative sample of children and adolescents of lower-middle and low socioeconomic status in Santiago, Chile. METHODS: A cross-section of 3022 primary-school students between the ages of 6 and 14 from middle-low and low-class schools of Santiago. Ten schools from the Primary Education Society (SIP) in Santiago, Chile, were selected at random. WC was measured under standardized procedures as instructed by the WHO (midpoint between lower costal margin and iliac crest). The population was categorized between percentiles 10 and 90 and divided by sex and age. RESULTS: WC tends to increase with age in both males and females, but no significant differences were found in the percentiles by age for boys and girls at any age range (p>0.05). In our sample, comparing Chilean children with other populations (British, Australian, European-American, African-American, Mexican - American and Colombian), Chilean children have shown a significantly greater WC (p<0.05). CONCLUSIONS: We present new WC reference values for Chilean children according to sex and age from a representative sample of Chilean population. These can be considered as a new anthropometric assessment tool for estimating cardiometabolic risk in Chilean children.

Utilidad de la determinación basal de la hormona luteinizante para determinar la activación del eje hipotalamo-hipofisiario-gonadal (HHG) / Basal luteinizing hormone values to determine activation of the hypothalamic-pituitary-gonadal axis

Background: The stimulation test with gonadotropin-releasing factor (GnRH) is considered the gold standard to study the activation of the hypothalamic-pituitary-gonadal axis (HPG). A maximum luteinizing hormone (LH) response of more than > 5 mIU/min in girls confirms the activation of the HPG axis. With the advent of more sensitive methods of LH measurement, such as immuno chemiluminescence (ICMA), basal LH values have been proposed to predict the response and replace the GnRH test. Aim: To determine which basal LH value correlates with a GnRH test > 5 uUI/ml. Material and Methods: We retrospectively analyzed LH values, measured by ICMA, in the basal period and after GnRH stimulation, in 120 girls aged 8 +/- 1 years (60 with activated axis and 60 without activation), during 2009. The sensitivity and specificity of the different values were determined by receiver operating characteristic (ROC) curves. Results: In patients with and without activation of the HPG axis, basal LH was 0.5 +/- 0.53 and 0.15 +/- 0.12 mUI/ml, respectively (p < 0.01). According to ROC curves, a basal LH value greater or equal than 0.4 mUI/ml had a specificity of 93.2 percent and a sensitivity of 61 percent to determine activation of the HPG axis. Conclusions: A basal LH > 0.4 mUI/ml in girls with precocious puberty has a specificity of 93.2 percent to determine activation of the HPG axis.

[Association of metabolic syndrome markers with abnormal alanine aminotransferase levels in healthy children]. / Marcadores de síndrome metabólico como predictores de elevación de alanino aminotransferasa en niños.

BACKGROUND: There is a high prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) among pediatric patients. The identification of clinical predictors of these conditions would allow a timely treatment. AIM: To evaluate the relationship between serum alanine aminotransferase levels and parameters of metabolic syndrome in asymptomatic school students without hepatic illness. SUBJECTS AND METHODS: A randomized sample of 175 children aged between 9 and 14 years (54% females) was selected, from a database of 3010 students living in Santiago, Chile. Weight, height, abdominal circumference, systolic and diastolic blood pressure were measured. A fasting blood sample was obtained to measure glucose, total cholesterol, HDL, LDL-cholesterol, triglycerides, alanine aminotransferase (ALT) and insulin levels. RESULTS: Forty percent of participants were obese, 17% had metabolic syndrome and 13.1% had abnormal ALT levels. Compared with children with normal ALT levels, the latter had significantly higher waist obesity, body mass index, systolic and diastolic blood pressure and triglycerides. However on multivariate analysis, only waist obesity was independently associated with abnormal ALT levels (adjusted odds ratio 3.93, 95% confidence intervals 1.44-10.78, p = 0.008). CONCLUSIONS: Only waist obesity was independently associated with abnormal ALT levels in this sample of children.

A new presentation of the chimeric CYP11B1/CYP11B2 gene with low prevalence of primary aldosteronism and atypical gene segregation pattern.

Familial hyperaldosteronism type I is caused by an unequal crossover of 11ß-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, giving rise to a chimeric CYP11B1/CYP11B2 gene (CG). We describe a family carrying a CG with high levels of free 18-hydroxycortisol but low prevalence of primary aldosteronism (PA) and an atypical CG inheritance pattern in a family of 4 generations with 16 adults and 13 children, we measured the arterial blood pressure, serum aldosterone, and plasma renin activity and then calculated the serum aldosterone:plasma renin activity ratio and urinary free 18-hydroxycortisol. We identified the CG by long-extension PCR and predicted its inheritance pattern. The CG was found in 24 of 29 subjects (10 children and 14 adults). In CG+ patients, hypertension and high 18-hydroxycortisol were prevalent (83% and 100%, respectively). High serum aldosterone:plasma renin activity ratio was more frequent in pediatric than adult patients (80% versus 36%; P<0.001). An inverse association between serum aldosterone:plasma renin activity ratio and age was observed (r=-0.48; P=0.018). Sequence analysis identified the CYP11B1/CYP11B2 crossover in a 50-bp region spanning intron 3 of CYP11B1 and exon 4 of CYP11B2. The CG segregation differs from an autosomal disease, showing 100% of CG penetrance in generations II and III. Statistical analysis suggests that inheritance pattern was not attributed to random segregation (P<0.001). In conclusion, we describe a family with an atypical CYP11B1/CYP11B2 gene inheritance pattern and variable phenotypic expression, where the majority of pediatric patients have primary aldosteronism. Most adults have normal aldosterone and renin levels, which could mask them as essential hypertensives.

Birth weight is inversely associated with blood pressure and serum aldosterone and cortisol levels in children.

CONTEXT: Low birth weight has been independently associated with adult hypertension, and renin-angiotensin system (RAS) plays a role in this connection. OBJECTIVE: To characterize the associations between birth weight (BW) and serum aldosterone (SA), serum cortisol, plasma renin activity (PRA) and blood pressure (BP). DESIGN: Cross-sectional study. SUBJECTS: Children from the community born at a gestational age >32 weeks. METHODS: Systolic and diastolic BP indices (SBPi and DBPi) were calculated using the observed BP/50th percentile BP for gender, age and stature. BW was transformed to a standard deviation score (SDS) for gestational age, whereas SA, serum cortisol and PRA were transformed using the natural log. RESULTS: We selected 288 subjects between the ages of 4·9 and 15·5 years (Females, 50%). After adjusting for body mass index (BMI) SDS and Tanner, multiple regression analysis revealed that BW (SDS) was both independently and inversely associated with the natural log of SA (ß = -0·065; P = 0·039), the natural log of serum cortisol (ß = -0·064; P = 0·009), SBPi (ß = -0·012; P = 0·020) and DBPi (ß = -0·023; P = 0·002). An association was not observed with PRA (P = 0·178) and aldosterone renin ratio (ARR) (P = 0·452). Serum cortisol levels were positively associated with SA (r = 0·125; P = 0·034), while an association with PRA (P = 0·251) and ARR (P = 0·052) was not observed. CONCLUSIONS: The results of this study demonstrate an inverse association between birth weight and blood pressure and serum aldosterone and cortisol levels. This association is independent of BMI and Tanner, suggesting foetal programming of the hypothalamic-pituitary-adrenal axis.

[Prevalence of hypertension in school age children and its association with obesity]. / Prevalencia de hipertensión arterial y su asociación con la obesidad en edad pediátrica.

BACKGROUND: Hypertension in children is a frequently overlooked problem that is an important cardiovascular risk factor. AIM: To determine the prevalence of hypertension among school age children. MATERIAL AND METHODS: Cross-sectional study of 2980 children aged 10 ± 2 years (48% females) from 10 schools of middle and lower class in Metropolitan Santiago. Blood pressure (BP) was measured in the sitting position on three occasions after a rest period, using a mercury sphygmomanometer with appropriate cuff arm diameter, averaging the results of the measurements. Systolic and diastolic hypertension were defined as blood pressure values over 95 percentile for age, sex and height. RESULTS: The overall prevalence of hypertension was 12.2% in women and 15% in men (p < 0.05). According to nutritional status, the prevalence was 6.7, 8.9,13.6 and 26% in underweight, eutrophic, overweight and obese children, respectively (p < 0.01). Compared with normal weight children, the risk of being hypertensive for overweight children was 1.6 (95% confidence intervals (CI) 1.2-2.3) and for obese children was 3.6 (95% CI 2.8-4.7). CONCLUSIONS: The studied children had a high prevalence of hypertension, that was directly related to a higher body mass index.

Prevalencia de hipertensión arterial y su asociación con la obesidad en edad pediátrica / Prevalence of hypertension in school age children and its association with obesity

Background: Hypertension in children is a frequently overlooked problem that is an important cardiovascular risk factor. Aim: To determine the prevalence of hypertension among school age children. Material and Methods: Cross-sectional study of 2980 children aged 10 ± 2years (48 percent females) from 10 schools of middle and lower class in Metropolitan Santiago. Blood pressure (BP) was measured in the sitting position on three occasions after a rest period, using a mercury sphygmomanometer with appropriate cuff arm diameter, averaging the results of the measurements. Systolic and diastolic hypertension were defined as blood pressure values over 95percentilefor age, sex and height. Results: The overall prevalence of hypertension was 12.2 percent in women and 15 percent in men (p < 0.05). According to nutritional status, the prevalence was 6.7, 8.9,13.6 and 26 percent in underweight, eutrophic, overweight and obese children, respectively (p < 0.01). Compared with normal weight children, the risk of being hypertensive for overweight children was 1.6 (95 percent confidence intervals (CI) 1.2-2.3) and for obese children was 3.6 (95 percent CI 2.8-4.7). Conclusions: The studied children had a high prevalence of hypertension, that was directly related to a higher body mass index.

Frequency of familial hyperaldosteronism type 1 in a hypertensive pediatric population: clinical and biochemical presentation.

Familial hyperaldosteronism type 1 is an autosomal dominant disorder attributed to a chimeric CYP11B1/CYP11B2 gene (CG). Its prevalence and manifestation in the pediatric population has not been established. We aimed to investigate the prevalence of familial hyperaldosteronism type 1 in Chilean hypertensive children and to describe their clinical and biochemical characteristics. We studied 130 untreated hypertensive children (4 to 16 years old). Blood samples for measuring plasma potassium, serum aldosterone, plasma renin activity, aldosterone/renin ratio, and DNA were collected. The detection of CG was performed using long-extension PCR. We found 4 (3.08%) of 130 children with CG who belonged to 4 unrelated families. The 4 patients with CG had very high aldosterone/renin ratio (49 to 242). In addition, we found 4 children and 5 adults who were affected among 21 first-degree relatives. Of the 8 affected children, 6 presented severe hypertension, 1 presented prehypertension, and 1 presented normotension. High serum aldosterone levels (>17.7 ng/dL) were detected in 6 of 8 subjects (range: 18.6 to 48.4 ng/dL) and suppressed plasma renin activity (≤0.5 ng/mL per hour) and high aldosterone/renin ratio (>10) in 8 of 8 children (range: 49 to 242). Hypokalemia was observed in only 1 of 8 children. We demonstrated that the prevalence of familial hyperaldosteronism type 1 in a pediatric hypertensive pediatric population was surprisingly high. We found a high variability in the clinical and biochemical characteristics of the affected patients, which suggests that familial hyperaldosteronism type 1 is a heterogeneous disease with a wide spectrum of presentations even within the same family group.