Boletín de la Sociedad de Pediatría de Aragón, La Rioja y Soria

[No abstract available

Hipopituitarismo. Una causa poco frecuente de retraso psicomotor

Sr. Editor: El hipopituitarismo es un síndrome clínico, resultante de la secreción insuficiente o ausencia completa de secreción de una o varias hormonas hipofisarias anteriores. Aunque típicamente el diagnóstico se suele realizar en período neonatal, en ocasiones, su primera manifestación puede ser un retraso psicomotor en loa lactantes, por lo que el diagnóstico precoz puede prevenir el deterioro neurocognitivo, evitando la aparición de secuelas neurológicas. Se presentan 2 casos de hipopituitarismo, diagnosticados a raíz de la presencia de retraso psicomotor en periodo de lactante: Caso 1 Recién nacida mujer a término, controlada por aumento craneal del diámetro biparietal y ventriculomegalia de ventrículos laterales con colpocefalia, sin signos de hipertensión intracraneal. Con 20 meses persiste ausencia de bipedestación y lenguaje; estudio analítico neurometabólico, carga viral de citomegalovirus, electroencefalograma, potenciales evocados auditivos, fondo de ojo, cariotipo y cribado neonatal normal. A los 21 meses presenta longitud de 70, 3 cm (–4, 8 DE) y peso de 6, 9 kg (–3, 71 DE), baja velocidad de crecimiento y estudio analítico hormonal compatible con déficit de hormona de crecimiento (GH), con el resto de estudios, incluido el tiroideo, normal. En el estudio genético arrays-CGH se detecta una deleción 1q25.2, asociado a haploinsuficiencia del gen LHX4..

Hypothalamyc hamartomas: Different ways of clinical debut. Cases report

Los hamartomas hipotalámicos son malformaciones no neoplásicas de sustancia gris compuestas por neuronas hiperplásicas. Suelen ser lesiones pequeñas localizadas en la base del cerebro, en el piso del tercer ventrículo y, generalmente, asintomáticas. Sin embargo, pueden ocurrir con alteraciones conductuales-cognitivas, crisis epilépticas y/o signos de pubertad precoz central en función de la localización en la que se encuentren. Se presentan dos pacientes de 2 años 8 meses y 7 años, con presencia de hamartomas hipotalámicos diagnosticados tras el estudio de pubertad precoz central. La paciente de menor edad presenta, además, crisis gelásticas, típicamente asociadas a hamartomas hipotalámicos. Tras los hallazgos clínicos y radiológicos, se trataron con análogos de gonadotropinas, y se observó una regresión de los signos puberales y una no progresión del tamaño de los hamartomas. Hypothalamic hamartomas are benign tumors of gray substance composed by hyperplasic neurons. They are usually asymptomatic small masses with extensions into the third ventricular cavity. In some instances they can cause cognitive behavioral alterations, seizures and/or central precocious puberty depending on the location. Here we present two cases of central precocious puberty due to hypothalamic hamartomas at 28/12 and 7 years of age. The younger patient also presents gelastic seizures, typically associated with hypothalamic hamartomas. After the clinical and radiological findings, they started treatment with GnRH analogues and a regression of the puberty signs without progression in the hamartomas size was observed

Hypogonadotropic hypogonadism in Klinefelter syndrome and hypothalamic-pituitary tumor

El síndrome de Klinefelter es la causa más frecuente de hipogonadismo hipergonadotropo en el varón. La supresión en la respuesta al estímulo con hormona liberadora de la hormona luteinizante en estos pacientes debe hacer sospechar como posible etiología una tumoración a nivel hipotalámico. Se presenta el caso de un paciente diagnosticado a los 4 meses con síndrome de Klinefelter mediante cribado neonatal, con cariotipo 47 XXY, en el que se realizan controles clínicos y analíticos seriados y se encuentran, a los 17 años, valores suprimidos de hormona luteinizante y hormona folículo estimulante. Inicia, posteriormente, cefalea y amaurosis de ojo izquierdo, y se encuentra, en una resonancia magnética cerebral, un tumor germinal mixto a nivel hipotalámico, que precisa tratamiento quirúrgico, quimioterapia y radioterapia, con respuesta favorable. Klinefelter Syndrome is the most frequent cause of hypergonadotropic hypogonadism in men. A flat response at luteinizing hormone releasing hormone stimulation test could be the first sign of hypothalamic tumor in these patients. We report the case of a patient diagnosed by neonatal screening with Klinefelter Syndrome, 47 XXY, that at 17 years follow-up presents analytical modification of the response to luteinizing hormone releasing hormone stimulation test with suppressed luteinizing hormone and follicle-stimulating hormone values; lately he presents with headache and loss of left eye vision. A magnetic resonance imaging of the brain showed a mixed germ cell hypothalamus tumor, requiring surgery, chemotherapy and radiotherapy with optimal response

Deficiencia de vitamina D en niños aragoneses sanos

Introducción: la principal acción de la vitamina D es mantener la concentración de calcio y fósforo dentro del rango fisiológico permitiendo el metabolismo normal y la mineralización ósea. Últimamente, se han descrito receptores de vitamina D en muchos tejidos y se ha relacionado la deficiencia de la vitamina D no solo con raquitismo y osteomalacia, sino también con mayor riesgo de diabetes, obesidad, enfermedades cardiovasculares, oncológicas, infecciosas y autoinmunes. Objetivo: el objetivo del estudio fue conocer la concentración de vitamina D en una población pediátrica sana y comprobar sus factores influyentes, así como analizar la situación actual de profilaxis de vitamina D y valorar la eficacia de las recomendaciones actuales. Métodos: se seleccionaron 107 pacientes sanos, de edades comprendidas entre uno y 15 años, que precisaron una analítica sanguínea como preoperatorio de cirugía menor, cuya patología no influyera en los parámetros del estudio. Resultados: la muestra estaba constituida en un 78, 5% por varones y presentaba una media de edad de 7, 17 ± 3, 79 años. La concentración media de vitamina D fue de 26, 07 ± 7, 11 ng/ml y hasta un 72, 9% presentaba niveles insuficientes. Se dividió la muestra en dos grupos: pacientes con hipovitaminosis D y pacientes con niveles óptimos de vitamina D. Se observó en el grupo con hipovitaminosis un predominio de varones, mayor índice de masa corporal y la presencia de fototipos extremos así como provenientes de padres inmigrantes. También presentaban mayor riesgo de hipovitaminosis los que no habían realizado profilaxis durante el primer año de vida. Conclusiones: se pone de manifiesto el alto porcentaje de población infantil sana con déficit de vitamina D y que las recomendaciones actuales de profilaxis no son llevadas a cabo por la población como recomiendan las guías actuales Background: the main action of vitamin D is to maintain the concentration of calcium and phosphorus within the physiological range, allowing normal metabolism and bone mineralization. Vitamin D receptors have recently been described in many tissues, therefore vitamin D deficiency has been related not only to rickets, but also to increased risk of diabetes, obesity, cardiovascular, oncological, infectious and autoimmune diseases. Objective: the aim of the study was to know the vitamin D concentration in a healthy pediatric population and to verify its influential factors, as well as to analyze the current situation of vitamin D prophylaxis and to evaluate the effectiveness of current recommendations. Methods: one hundred and seven healthy patients aged between one and 15 years were selected, who required a blood test as a preoperative minor surgery and whose pathology did not influence the parameters of the study. Results: the sample analyzed had a total of 78.5% males and a mean age of 7.17 ± 3.79 years. Mean values of vitamin D were 26.07 ± 7.11 ng/ml; up to 72.9% had insufficient levels. The sample was divided into two groups: patients with hypovitaminosis D and patients with optimal vitamin D levels. A predominance of males with a higher body mass index, from immigrant parents, and the presence of extreme phototypes were observed in the hypovitaminosis group. There was also a higher risk of hypovitaminosis in those who had not performed prophylaxis during the first year of life. Conclusions: the high percentage of healthy children with vitamin D deficiency is evident, and current recommendations for prophylaxis are not carried out by the population as recommended by current guidelines

Hiperplasia suprarrenal congénita debida a deficiencia de 17a-hidroxilasa: a propósito de una nueva mutación en el gen CYP17A1

La enzima P450c17 cataliza 2 reacciones diferentes: 17a-hidroxilación de la progesterona y pregnenolona y segmentación de la unión del carbono 17-20 a partir de la 17,20 liasa para producir andrógenos suprarrenales. Esta enzima está codificada por el gen CYP17A1. Se presenta una paciente de 14 años con retraso en el desarrollo puberal y presión arterial elevada para su talla y edad. Cariotipo 46,XX. En el estudio hormonal destaca hipogonadismo hipergonadotropo, así como una insuficiencia suprarrenal y exceso mineralocorticoideo. El estudio genético mostró una mutación en homozigosis en el gen CYP17A1 (c.753+1G>A), no descrita previamente, la cual es responsable de la fisiopatología de la deficiencia de 17a-hidroxilasa. Esta entidad es una forma rara de hiperplasia suprarrenal congénita. Normalmente la enfermedad suele pasar desapercibida hasta la adolescencia o el inicio de la vida adulta y se debería sospechar ante individuos 46,XY con genitales ambiguos o 46,XX con retraso puberal que asocia hipertensión y/o hipopotasemia. P450c17 enzyme catalyses two different reactions: the 17a-hydroxylation of progesterone and pregnenolone, and segmenting the carbon 17-20 binding from the 17,20 lyase producing adrenal androgens. This enzyme is coded by the CYP17A1 gene. The case is presented of a 14 year old patient with delayed pubertal development and a high blood pressure for height and age. 46,XX karyotype. Hormonal studies highlighted hypergonadotropic hypogonadism, adrenal insufficiency and mineralocorticoid excess. Subsequent genetic studies showed a homozygous mutation in the CYP17A1 gene (c.753+G>A), not previously described, which is responsible for the pathophysiology of 17a-hydroxylase deficiency. This entity is a rare form of congenital adrenal hyperplasia. The disease often goes unnoticed until adolescence or early adult life, and should be suspected in 46,XY individuals with ambiguous genitalia or 46,XX with delayed puberty associated with hypertension and/or hypokalaemia

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true