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Resumen Antecedentes y objetivo Los ninos nacidos pequenos para la edad gestacional (PEG) tienen mayor riesgo de presentar anomalias en el neurodesarrollo y la capacidad cognitiva. El objetivo del estudio es determinar el neurodesarrollo de ninos PEG durante los primeros 2 anos de vida y establecer la influencia de datos antropometricos, la edad gestacional, la gemelaridad y factores perinatales. Pacientes y metodo Estudio observacional, prospectivo, descriptivo y analitico de la valoracion neurocognitiva realizada, con el test de Brunet-Lezine, a ninos PEG (n = 91) desde los 3 a los 24 meses de edad, comparandola con controles propios. Resultados Noventa y un ninos PEG, 47% mujeres, 83,5% gestaciones unicas; edad gestacional media 37,7 semanas (desviacion estandar [DE] 2,1). Peso al nacimiento 2.053,3 g (DE 433,1), longitud 43,9 cm (DE 2,6) y perimetro cefalico 31,7 cm (DE 1,7). La poblacion PEG presenta un neurodesarrollo significativamente inferior al de la poblacion control, con tendencia a mejorar durante los primeros 2 anos de vida. No existen diferencias por sexos. Los ninos PEG nacidos de gestaciones multiples presentan resultados neurocognitivos inferiores unicamente durante el primer ano de vida. Existe una correlacion directa y positiva entre el peso, la longitud y el perimetro cefalico con el desarrollo neurocognitivo a los 6, 9, 12 y 18 meses. La edad gestacional se correlaciona con un mejor neurodesarrollo a los 3 y 6 meses. Conclusiones Los ninos nacidos PEG presentan un neurodesarrollo inferior al de la poblacion control. Una mayor afectacion del peso, la longitud y el perimetro cefalico al nacimiento se correlaciona con peores datos neurocognitivos. La multiparidad no influye significativamente en la evolucion del neurodesarrollo.

Resumen Introduccion La talla baja es motivo de consulta frecuente en Endocrinologia Pediatrica, precisando en ocasiones tratamiento con hormona del crecimiento (GH). El objetivo del estudio fue analizar la respuesta al tratamiento en funcion de su inicio en la etapa puberal o prepuberal y analizar el posible beneficio de un comienzo precoz. Pacientes y metodos Estudio longitudinal, retrospectivo y observacional en 139 pacientes tratados por deficit de GH idiopatico (grave o parcial) hasta talla adulta. Principales variables estudiadas: a) antecedentes familiares: talla materna, paterna y genetica; b) antecedentes perinatales; c) antropometria durante el seguimiento y al inicio puberal: peso, talla, indice de masa corporal, y d) variables durante el seguimiento y al inicio puberal: velocidad de crecimiento, edad osea y pronostico de crecimiento. Variables de respuesta final: talla adulta, talla adulta respecto a talla genetica, talla adulta respecto al pronostico de crecimiento inicial, talla adulta respecto a talla al inicio del tratamiento y talla adulta respecto a talla al inicio puberal. Resultados La ganancia puberal total fue de 0,84 ± 0,6 DE. Un 61,9% de los pacientes iniciaron tratamiento con GH en prepubertad. El inicio del tratamiento en la etapa prepuberal y una mayor ganancia puberal total se relacionaron con una mejor talla final (p = 0,001, y r = 0,507, p = 0,00 respectivamente). Ademas, una mayor duracion del tratamiento en la prepubertad se correlaciono con una mejor respuesta final (r = 0,328, p = 0,00). Conclusiones El inicio del tratamiento en la prepubertad y una mayor duracion durante este periodo son factores determinantes para alcanzar una mejor respuesta a largo plazo. La ganancia puberal total fue mayor en los pacientes que iniciaron el tratamiento en etapa puberal.

Resumen Introduccion La talla baja es el principal motivo de consulta en endocrinologia pediatrica, precisando en ocasiones tratamiento con hormona de crecimiento. Objetivo Evaluar la relacion de los factores de buena respuesta al tratamiento con hormona de crecimiento durante el primer ano con la respuesta final y valorar si existen diferencias segun el tipo de deficit. Pacientes y metodos Estudio longitudinal, retrospectivo y observacional en 139 pacientes tratados por deficit de hormona de crecimiento idiopatico (severo o parcial) hasta talla adulta. Criterios de buena respuesta en el primer ano de tratamiento: a) incremento velocidad de crecimiento ≥3 cm/ano, b) velocidad de crecimiento ≥ 1 desviacion estandar (DE), c) incremento talla ≥ 0,5 DE, d) incremento talla ≥ 0,3 DE. Estudio del indice de repuesta al tratamiento al primer y segundo ano. Variables de respuesta final: talla adulta, talla adulta respecto a talla genetica, talla adulta respecto al pronostico de crecimiento inicial y talla adulta respecto a talla al inicio del tratamiento. Resultados El tratamiento produce una ganancia de talla adulta con respecto a la talla genetica de 0,06 ± 0,7 DE. Los pacientes buenos respondedores el primer ano de tratamiento presentaron una mejor respuesta final (velocidad de crecimiento ≥ 3 cm, p = 0,000; velocidad de crecimiento ≥ 1 DE, p = 0,008; ganancia talla ≥ 0,5 DE, p = 0,007; ganancia talla ≥ 0,3 DE, p = 0,006), asi como los pacientes con deficit severo (p = 0,04). El indice de respuesta al tratamiento al primer ano asocia una mejor respuesta final (r = 0,249; p = 0,003), manteniendose el segundo ano (r = 0,294; p = 0,01). Conclusiones El tratamiento con hormona de crecimiento alcanza la talla genetica. El porcentaje de buenos respondedores varia segun el criterio. La respuesta al primer ano de tratamiento y un deficit severo son factores determinantes para conseguir una buena respuesta final.

Introduction Osteogenesis imperfecta (OI) is a heterogeneous genetic disease manifesting as bone fragility and fractures. Patients and methods Retrospective descriptive study analysing clinical and genetic features, and treatment of patients with OI. Results Forty patients were included; 32.5% males, 67.5% females; 29 children, 11 adults. Number of fractures at diagnosis with mild OI was 4.6±6.4 (average age at diagnosis 7.8±12.8years), with moderate OI 1.7±2.4 (age at diagnosis .04±.3years), in severe OI 3.7±2.1 and in extremely severe forms 12.5±7.8, both groups diagnosed at birth. Genetic study in 32 patients, 25 with a positive genetic study (pathogenic/probably pathogenic variant). COL1A1 gene was the most frequently affected. In 7 patients, no pathogenic or probably pathogenic variant was found (5 diagnosed by biochemical study of typeI collagen). Nineteen patients were treated with bisphosphonates; 7 combined with growth hormone. The patients treated with bisphosphonates showed clinical improvement (reduction of bone pain and/or irritability) and reduction of fractures. Conclusions The COL1A1 gene is the most frequently affected. OI patients should receive multidisciplinary management and bisphosphonates can improve their quality of life.

Resumen Introduccion La osteogenesis imperfecta (OI) es una enfermedad genetica heterogenea manifestada como fragilidad osea y fracturas. Pacientes y metodos Estudio descriptivo retrospectivo analizando caracteristicas clinicas, geneticas y tratamiento de pacientes diagnosticados de OI (1989-2017) en el Hospital Universitario Miguel Servet, Zaragoza (Endocrinologia Pediatrica y Reumatologia). Resultados Incluidos 40 pacientes; 32,5% varones, 67,5% mujeres; 29 ninos, 11 adultos. Media de fracturas al diagnostico en OI leve 4,6 ± 6,4 (edad media al diagnostico 7,8 ± 12,8 anos), en OI moderada 1,7 ± 2,4 (edad media al diagnostico 0,04 ± 0,3 anos), en OI grave 3,7 ± 2,1 y en OI muy grave 12,5 ± 7,8, ambos grupos diagnosticados al nacimiento. Estudio genetico en 32 pacientes, 25 con variante patogenica/probablemente patogenica, siendo COL1A1 el gen mas frecuentemente afectado. En 7 pacientes no fue encontrada la variante responsable, 5 con confirmacion diagnostica (estudio bioquimico colageno I). Tratamiento con bifosfonatos 19 pacientes; 7 asociando hormona de crecimiento. Los tratados con bifosfonatos han presentado mejoria clinica (reduccion de dolor oseo y/o irritabilidad) y reduccion del numero de fracturas. Conclusiones El gen COL1A1 es el mas frecuentemente afectado en nuestros pacientes. El tratamiento debe ser multidisciplinar y el uso de bifosfonatos proporciona mejoria.

There are situations of short stature, with a normal stimulus test for GH, but decreased nocturnal secretion in which there could be a benefit with GH treatment.To assess adult height and height gain in patients with neurosecretory dysfunction diagnosis treated with growth hormone.Longitudinal, retrospective and observational study including 61 patients treated with growth hormone after diagnosis of neurosecretory dysfunction who have already reached adult height. Variables such as adult height gain, growth rate, growth prognosis variation and IGF-I and IGFBP-3 were evaluated. Variables related to a good response in the first year have also been calculated, using the Index of responsiveness (IoR).GH treatment produces an improvement in growth rate and height, observing an increase in adult height with respect to initial height of 1.15±0.60 SD, height with respect to genetic height of -0.015±0.62 SD and adult height with respect to the initial growth prognosis 0,74±1,13 DE. The IoR in the first year is associated with a greater increase in height in the first year (p=0.000), with a greater adult height (p=0.000) and with a greater gain in adult height compared to its initial height (p=0.039).Patients with growth delay due to neurosecretory dysfunction of GH show a good response to treatment with rhGH, observing a significant height gain in their genetic size and improving their initial growth prognosis.

Allan-Herndon-Dudley syndrome is a rare X-linked genetic disorder, caused by a deficiency of the monocarboxylate transporter 8 (MCT8), a specific transporter of thyroid hormones, with functions mainly at the brain level. The syndrome produces an early onset of severe neurological disorder, in which hypotonia predominates.To present a rare case with an unexpected diagnosis, highlighting the usefulness of requesting a complete thyroid profile in every hypotonic male infant without a specific cause.A 10-month-old male infant with severe axial and peripheral hypotonia, global weakness with little spontaneous mobility, without head support or stable sitting. Complete metabolic and peripheral neurophysiological studies were performed. Genetic studies for spinal muscular atrophy, Prader Willi syndrome, and myotonic dystrophy were also performed. The trio exome analysis detected a probably pathogenic variant c.359CT;p.(Ser120Phe), hemizygous in exon 1 of the SLC16A2 gene, inherited from the mother. Thyroid abnormalities as increased free triiodothyronine (T3) and thyroid-stimulating hormone (TSH), and delayed myelination were ob served.MCT8 deficiency should be considered in the case of the male infant with unex plained hypotonia and weakness without a determined cause. The diagnosis is guided by a thyroid profile including free T3 hormone, because it presents a characteristic thyroid profile with decreased free thyroxine (T4), increased free T3, and normal or slightly elevated TSH levels. In this case, the implementation of the trio exome analysis allows establishing an early certain diagnosis.

Resumen Introduccion El aumento en la supervivencia de la leucemia aguda (LA) infantil conlleva un incremento de morbilidades a largo plazo que acompanado del impacto ocasionado por el tratamiento puede alterar la calidad de vida ( C V). Objetivo Evaluar la prevalencia de comorbilidades cronicas, CV y predictores de su desarrollo en supervivientes de LA. Metodos Estudio transversal de una cohorte de 54 individuos con mas de 10 anos de supervivencia tras diagnostico de LA. Se evaluaron la presencia de comorbilidades y la CV global, fisica y mental mediante cuestionario SF-36. Resultados El 53,7% presento ≥ 1 comorbilidad cronica (24,7% hipotiroidismo; 20,3% obesidad; 14,8% sindrome metabolico; 18,5% disfuncion cardiaca subclinica). El 20,3% de ellas fueron comorbilidades graves. El 73,3% de LA alto riesgo y el 66,6% de los tratados con radioterapia o trasplante presentaron comorbilidad tardia, p Conclusiones Los supervivientes de LA presentan una alta prevalencia de comorbilidades cronicas, asociadas al tratamiento recibido. A pesar de que estas influyen en alguna de las subescalas de su CV, la percepcion global fue muy buena, incluso superior a la media de la poblacion general.

Children born small for gestational age (SGA) show higher risk of neurodevelopmental and cognitive abnormalities. The objective of this study is to determine in children born SGA the neurodevelopment during the first 2 years of life and to establish the influence of anthropometric data, gestational age, multiple gestation and perinatal factors.Observational, prospective, descriptive and analytical study of the neurocognitive assessment performed, with Brunet-Lézine test, on SGA children (n = 91) from 3 to 24 months of age, comparing with own controls.Ninety-one SGA children, 47% girls, 83.5% single pregnancies; mean gestational age 37.7 weeks (standard deviation (SD) 2.1). Weight at birth 2053 g (SD 433.1), length 43.9 cm (SD 2.6) and head circumference 31.7 cm (SD 1.7). The SGA population shows significantly lower neurodevelopment than the control population, with a tendency to improve during the first 2 years of life. There are no differences by sex. SGA children born to multiple gestations have lower neurodevelopment only during the first year of life. There is a direct and positive correlation between weight, length and head circumference with neurocognitive development at 6, 9, 12 and 18 months. Gestational age correlated with better neurodevelopment at 3 and 6 months.Children born SGA present lower neurodevelopment than the control population. A greater impact on weight, length, and head circumference at birth is correlated with poorer neurocognitive development. Multiparity does not show significant influence on neurodevelopment evolution.

Purpose Adherence to growth hormone (GH) treatment impacts clinical outcomes. The aim of this study is to assess the impact of adherence to rhGH treatment (2 years) on auxological outcomes. Methods Multicentric, retrospective observational study in rhGH-naive GHD/SGA children treated with Saizen (R) during >= 2 years. Growth response was assessed by evaluating the change in height standard deviation score (Delta H SDS) and the index of responsiveness (IoR). Adherence was monitored using EasyPod (TM) Connect device. Results A total of 110 patients (3 Spanish centers) were evaluable (GHD n = 76, SGA n = 34). Adherence was 95.6 and 93.9% (year 1, 2). SGA and GHD children showed an increase of 0.6 cm/year and 1.1 cm/year for each 10% adherence modification. Lower adherence was observed in patients with lower pretreatment height velocity (HV) and in patients whose parents had a lower level of education. A positive correlation between index of responsiveness (IoR) during the first and second years with HV SDS during the second year and between IoR2 and adherence (year 1, 2) was observed. The frequency of patients with HV > 1 SD was higher (p = 0.025) among patients with adherence >90%. The best model to predict the height gain(cm) reaching an adjusted R squared of 0.489 involved percentage of adherence, Tanner stage, pretreatment HV, dose of rhGH, and whether the treatment was initiated before or after puberty. Conclusions Adherence during the first 2 years of response was very high >90% and showed a negative association with age, pretreatment HV and treatment duration and a positive correlation with the level of parent education.

Resumen: Introducción: La pubarquia precoz (PP) es generalmente considerada como una enfermedad benigna, pero puede ser el primer signo de una enfermedad subyacente. Objetivo: Analizar la etiología y la evolución de parámetros antropométricos, analíticos y de riesgo metabólico, en pacientes con PP. Material y métodos: Estudio retrospectivo, descriptivo y analítico, de 92 pacientes afectos de PP. Se evaluaron medidas antropométricas y analíticas, la edad ósea y marcadores de metabolismo lipídico. Resultados: Muestra de 92 pacientes (67 mujeres y 25 varones) con PP, con una edad media de 7,1 ± 0,6 años las mujeres y 8,3 ± 0,7 los varones. El 7,7% fueron pequeños para la edad gestacional. La edad ósea estaba adelantada (1,2 ± 0,1 años). Veintiún pacientes fueron clasificados como PP idiopática (23%), 60 como adrenarquia precoz idiopática (65%) y 11 como hiperplasia suprarrenal congénita no clásica (12%). La pubertad se mostró adelantada respecto a la media (11 ± 0,9 años en varones versus 9,9 ± 0,8 años en mujeres), así como la edad de la menarquia (11,8 ± 1,1 años), p

Cardiac events are the most common nonmalignant cause of death in childhood cancer survivors. This population has an increased risk of morbimortality, probably secondary to the treatment side effects. The objective was to determine the prevalence and determinants of left ventricular dysfunction in a cohort of long term childhood acute leukemia survivors treated with potentially cardiotoxic therapies.Retrospective study with at least 10 years of follow-up, diagnosed between 1999 and 2003. The reduction percentage of the fractional shortening and ejection fraction was calculated from the diagnosis to the end of treatment and 10 years after the end of treatment. The factors associated with their decrease were analyzed.The fractional shortening and ejection fraction experienced a significant decrease 10 years after the end of treatment from 38.16 to 32 and 69.08 to 60.79, respectively. Reduction was more pronounced during the evaluation of the first year after treatment (-10.3% and -8.96%, P0.05). Associated with high tumor risk and adjuvant treatment with hematopoietic stem cell transplantation and total body radiation. No differences were found in the total anthracycline doses received. Patients with the greatest decrease had a lower age at the time of diagnosis (mean 5.7 ± 4.5 years), 62.5% (5/8) less at 5 years, and 75% received radiotherapy and hematopoietic stem cell transplantation.There is already a significant decrease in the fractional shortening and ejection fraction during the first year after the end of the treatment, which is maintained 10 years after the end of treatment. Associated with high tumor risk and with total body radiation treatment and hematopoietic stem cell transplantation.

Heart disease is the leading cause of non-cancer death in childhood cancer survivors. to determine the prevalence of subclinical cardiac dysfunction using speckle tracking and compare its results with those obtained by classical methods of assessing left ventricular function and its relationship with different factors to identify the population at higher risk. Echocardiographic assessment of left ventricular function included ejection fraction, tissue Doppler, longitudinal/circumferential strains and biochemical parameters (troponin-T and Pro-BNP) in a cohort of 57 survivors of childhood acute leukaemia with at least 10 years since diagnosis. Ventricular dysfunction was found in 5.2% of patients in M-mode (ejection fraction—EF

Resumen: Objetivo: Evaluación de parámetros clínicos y analíticos que actúen como predictivos de respuesta al tratamiento con hormona de crecimiento (rhGH) a largo plazo en pacientes con síndrome de Turner. Material y métodos: Estudio retrospectivo de 25 niñas diagnosticadas de síndrome de Turner, de las cuales 17 recibieron tratamiento con rhGH y fueron controladas hasta alcanzar la talla adulta. Se determinaron diferentes variables auxológicas, analíticas, genéticas y farmacológicas a lo largo de su seguimiento en dichas consultas. Se realizó un estudio descriptivo y analítico mediante regresión lineal, con valoración de la respuesta al tratamiento a corto (12 meses) y a largo plazo. Resultados: Se observó una respuesta favorable a corto plazo valorada en ganancia de velocidad de crecimiento en el 66,6% de los casos (velocidad de crecimiento > 3 cm/año a los 12 meses de tratamiento respecto a la previa). También se evidenció una respuesta favorable a largo plazo, valorada en una ganancia de talla total de 42,82 ± 21,23 cm (1,25 ± 0,76 SDS). Las pacientes ganaron una media de 9,59 ± 5,39 cm (1,68 ± 1,51 SDS) respecto a su pronóstico de crecimiento previo al tratamiento. Conclusiones: El presente estudio evidencia como factores predictivos de buena respuesta al tratamiento con rhGH a largo plazo en orden de importancia: A) dosis de rhGH al inicio del tratamiento, B) tiempo de tratamiento con rhGH hasta inicio de terapia estrogénica, C) incremento en los niveles de IGF1 e IGFBP-3 durante el primer año de tratamiento y D) velocidad de crecimiento en el primer año de tratamiento. Abstract: Objective: The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. Material and methods: A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. Results: A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3 cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82 ± 21.23 cm (1.25 ± 0.76 SDS), with an adult height gain of 9.59 ± 5.39 cm (1.68 ± 1.51 SDS). Conclusions: Predictors of good response to growth hormone treatment are: A) initial growth hormone dose, B) time on growth hormone treatment until starting oestrogen therapy, C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and D) height gain velocity in the first year of treatment.

Background and objective Recombinant human growth hormone (rhGH) treatment in small for gestational age (SGA) children has been effective, although there is significant variability in the response. Adult height and the factors that determine the long-term response are evaluated. Patients and design A retrospective study of 80 patients born SGA with short stature treated with rhGH and followed until adult height (23 males). Results The group starting treatment pre-puberty reached a higher Adult height (−1.4 ± 0.6 vs. −1.9 ± .6 in pubertal children), the highest final height gain was achieved in those treated for at least 2 years prepuberty (1.32 ± .5 SDS). Factors associated with greater adult height gain were: (a) less height, weight and BMI at start of treatment, (b) lower chronological and bone age with lower IGF-I before treatment, (c) greater distance to target height, (d) higher growth velocity the first and second year of treatment, and higher height gain before and during puberty. The percentage of patients with good response in the first year ranged from 46.6% to 81.6% depending on the criteria. Growth velocity increase ≥3 cm/first year correlated best with long-term response. Conclusion rhGH treatment in children born SGA produced a varying increase in adult height that allowed them to reach their adult height. The best results occurred in the prepubertal group and did not depend on pituitary GH response.

Survival of childhood acute lymphoblastic leukaemia involves an increasing risk of long-term morbidities. Due to the impact of cancer treatment and comorbidities, AL survivors may experience a decrease in their health-related quality of life.We aimed to describe the long-term comorbidities, related quality of life and their development predictors in these survivors.cross-sectional study of 54 survivors aged ≥18 and who have a survival rate of more than 10 years. Quality of life was assessed by personal interview using SF-36 questionnaire.53.7% of AL survivors developed more than one comorbidity (24.7% hypothyroidism; 20.3% obesity; 14.8% metabolic syndrome; 18.5% subclinical cardiac dysfunction); 20.3% of them were severe. 73.3% of high-risk leukaemias and 66.6% of patients treated with radiotherapy or stem cells transplantation reported long-term comorbidity, P.05. Global quality of live score was: 86.3 (14) (classified as very good). Patients with high-risk acute leukaemia (83.2 vs. 89.5), severe long-term comorbidities (80.4 vs. 89.7) and females (81.8 vs. 89.9), reported worse quality of life, P.05. Physical summary score was worse in: obese (80 vs. 92) and hypothyroid (84.9 vs. 92.4) and radiotherapy-treated survivors (82.3 vs. 87.5); mental summary was worse in survivors with hypogonadism (68.2 vs. 86.3) and trasplanted patients (77.2 vs. 83.1), P.05.Acute leukaemia survivors reported an increase prevalence of chronic comorbidities, related to cancer-treatment. Despite a decrease in scores for certain physical or mental items, global quality of life was very good in all acute leukaemia survivors, even better than compared with the general population.

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.

X-linked adrenoleukodystrophy is the most common peroxisomal disorder. This disease is caused by a defect in the ABCD1 gen. Saturated very long chain fatty acids are accumulated in serum, adrenal cortex and central nervous system white matter. The clinical spectrum is characterized by progressive neurological dysfunction and adrenal insufficiency with a devastating prognosis. We report a first case of X-linked adrenoleukodystrophy with fatal evolution which identified two asymptomatic family members and established a preventive treatment. Although there is no definitive cure, we stress the importance of family study and evaluation of the individual in situation of risk to establish an early preventive treatment and to give in each particular situation suitable professional advice.

Introduction: Premature pubarche (PP) is generally thought to be a benign condition, but it can also be the first sign of underlying disease. Objective: To analyse the aetiology and the evolution of the anthropometric, analytical and metabolic risk parameters of a group of patients with PP. Material and methods: A descriptive and analytical retrospective study of 92 patients affected by PP. Anthropometry, analyses, bone age and indicators of lipid metabolism were all evaluated. Results: The sample included 92 patients with PP (67 female and 25 male), with a mean age of 7.1 ± 0.6 for girls and 8.3 ± 0.7 for boys. Small for gestational age was recorded in 7.7%. There was an accelerated bone age (1.20 ± 0.1 years). A total of 21 patients were classified as idiopathic (23%), 60 as idiopathic premature adrenarche (65%), and 11 with non-classic congenital adrenal hyperplasia (12%). Puberty was reached early (11 + 0.9 years old in boys and 9.9 ± 0.8 in girls), as was menstruation age (11.8 + 1.1 years old), P

Introduction For the diagnosis of patients with growth disorders, visual inspection and the measurement of body segments may provide important information. The most commonly used method is the assessment of the sitting/standing height (SH/SH) ratio and its comparison to aged matched controls. Objective To establish the normal values of the sitting/standing height ratio in a normal Aragonese population from birth to 18 years old. Population and methods Longitudinal study from birth to 18 years old. Length (up to 3 years old), standing height (as of 2 years old) and sit-ting height were recorded. Percentiles for sitting/ standing height ratio were determined. Results The study included 165 male children and 167 female children. The values of the sitting/standing height ratio decrease from birth both in males and females (0.656 and 0.647, respectively) until the onset of puberty (0.514 and 0.519); and later start to slightly increase until reaching the definitive adult ratio (0.52 and 0.53, respectively). Conclusion Sitting/standing height ratio values are presented in normal male and female children up to 18 years old. This ratio decreases from birth to puberty and then slightly increases until reaching the final adult ratio.

Introduction. For the diagnosis of patients with growth disorders, visual inspection and the measurement of body segments may provide important information. The most commonly used method is the assessmentof the sitting/standing height (SH/SH) ratio and its comparison to aged matched controls. Objective. To establish the normal values of the sitting/standing height ratio in a normal Aragonese population from birth to 18 years old. Population and Methods.Longitudinal study from birth to 18 years old. Length (up to 3 years old), standing height (as of 2 years old) and sitting height were recorded. Percentiles for sitting/ standing height ratio were determined. Results. The study included 165 male children and 167 female children. The values of the sitting/standing height ratio decrease from birth both in males and females (0.656 and 0.647, respectively) until the onset of puberty (0.514 and 0.519); and later start to slightly increase until reaching the definitive adult ratio (0.52 and 0.53, respectively). Conclusion. Sitting/standing height ratio values are presented in normal male and female children up to 18 years old. This ratio decreases from birth to puberty and then slightly increases until reaching the final adult ratio.

Introducción: saber diagnosticar y tratar la obesidad se ha convertido en el mayor reto del siglo XXI, debido al aumento de su prevalencia.Objetivos: determinar los valores de normalidad de perímetro abdominal (PA) e índice de masa corporal (IMC) según edad y sexo en población española sana.Métodos: estudio longitudinal observacional realizado entre 1980 y 2014. Se incluyeron 165 niños y 169 niñas recién nacidas, recogiendo datos de forma anual hasta los 18 años (74 varones y 92 mujeres), y posteriormente a los 28 años (42 varones y 45 mujeres). Se realizó medición de peso, longitud/talla y perímetro abdominal. Se calcularon los percentiles (P3, P10, P25, P50, P75, P90, P97) de IMC y PA según edad y sexo.Resultados: se presentan datos evolutivos de IMC y PA durante la infancia, destacando cómo aumentan los valores entre los 18 y 28 años de los percentiles superiores al p50, sobre todo en mujeres. Existe una correlación positiva en relación al PA entre el valor obtenido a los 3 años con el valor de los 18 años y de los 28 años tanto en varones (r = 0,722 y r = 0,605, p = 0,000, respectivamente) como en mujeres(r = 0,922, r = 0,857, p = 0,000, respectivamente). Y entre los 18 y 28 años (r = 0,731, p = 0,000 para varones y r = 0,961, p = 0,000 para mujeres).Conclusión: se presentan valores de normalidad de PA e IMC según edad y sexo, que podrán utilizarse como herramienta de referencia para identificar a personas con riesgo de desarrollar enfermedades cardiovasculares o diabetes.

Introducción: saber diagnosticar y tratar la obesidad se ha convertido en el mayor reto del siglo XXI, debido al aumento de su prevalencia. Objetivos: determinar los valores de normalidad de perímetro abdominal (PA) e índice de masa corporal (IMC) según edad y sexo en población española sana. Métodos: estudio longitudinal observacional realizado entre 1980 y 2014. Se incluyeron 165 niños y 169 niñas recién nacidas, recogiendo datos de forma anual hasta los 18 años (74 varones y 92 mujeres), y posteriormente a los 28 años (42 varones y 45 mujeres). Se realizó medición de peso, longitud/talla y perímetro abdominal. Se calcularon los percentiles (P3, P10, P25, P50, P75, P90, P97) de IMC y PA según edad y sexo.Resultados: se presentan datos evolutivos de IMC y PA durante la infancia, destacando cómo aumentan los valores entre los 18 y 28 años de los percentiles superiores al p50, sobre todo en mujeres. Existe una correlación positiva en relación al PA entre el valor obtenido a los 3 años con el valor de los 18 años y de los 28 años tanto en varones (r = 0,722 y r = 0,605, p = 0,000, respectivamente) como en mujeres(r = 0,922, r = 0,857, p = 0,000, respectivamente). Y entre los 18 y 28 años (r = 0,731, p = 0,000 para varones y r = 0,961, p = 0,000 para mujeres).Conclusión: se presentan valores de normalidad de PA e IMC según edad y sexo, que podrán utilizarse como herramienta de referencia para identificar a personas con riesgo de desarrollar enfermedades cardiovasculares o diabetes.

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 2(8/12) 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.

Objective: The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. Material and methods: A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. Results: A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3 cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82 ± 21.23 cm (1.25 ± 0.76 SDS), with an adult height gain of 9.59 ± 5.39 cm (1.68 ± 1.51 SDS). Conclusions: Predictors of good response to growth hormone treatment are: (A) initial growth hormone dose, (B) time on growth hormone treatment until starting oestrogen therapy, (C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and (D) height gain velocity in the first year of treatment. Resumen: Objetivo: Evaluación de parámetros clínicos y analíticos que actúen como predictivos de respuesta al tratamiento con hormona de crecimiento (rhGH) a largo plazo en pacientes con síndrome de Turner. Material y métodos: Estudio retrospectivo de 25 niñas diagnosticadas de síndrome de Turner, de las cuales 17 recibieron tratamiento con rhGH y fueron controladas hasta alcanzar la talla adulta. Se determinaron diferentes variables auxológicas, analíticas, genéticas y farmacológicas a lo largo de su seguimiento en dichas consultas. Se realizó un estudio descriptivo y analítico mediante regresión lineal, con valoración de la respuesta al tratamiento a corto (12 meses) y a largo plazo. Resultados: Se observó una respuesta favorable a corto plazo valorada en ganancia de velocidad de crecimiento en el 66,6% de los casos (velocidad de crecimiento > 3 cm/año a los 12 meses de tratamiento respecto a la previa). También se evidenció una respuesta favorable a largo plazo, valorada en una ganancia de talla total de 42,82 ± 21,23 cm (1,25 ± 0,76 SDS). Las pacientes ganaron una media de 9,59 ± 5,39 cm (1,68 ± 1,51 SDS) respecto a su pronóstico de crecimiento previo al tratamiento. Conclusiones: El presente estudio evidencia como factores predictivos de buena respuesta al tratamiento con rhGH a largo plazo en orden de importancia: A) dosis de rhGH al inicio del tratamiento, B) tiempo de tratamiento con rhGH hasta inicio de terapia estrogénica, C) incremento en los niveles de IGF1 e IGFBP-3 durante el primer año de tratamiento y D) velocidad de crecimiento en el primer año de tratamiento.

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.

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.

The study of the common carotid artery using ultrasound, ever has greater significance for the prevention, treatment and evaluation of the risk of developing cardiovascular disease. Increased intima-media thickness is associated with the presence of other cardiovascular, cerebrovascular disease and the development of atherosclerosis in both adults and pediatric populations.A cross-sectional study in 202 healthy children aged between 4 and 15 years. It has been analyzed auxological data, systolic and diastolic blood pressure and carotid intima-media thickness.There are 100 men and 102 women, with no differences among them about sex; it is shown graphical representations of the values of carotid intima-media thickness in the total sample and by gender. There is a positive correlation between carotid intima-media thickness with age (r = 0.229, p0.05), weight (r = 0.228, p0.05), height (r = 0.265, p0.01) and BMI (r = 0.212, p0.05).Identification of modifiable risk factors should be our priority in clinical practice. Thus, in any health program it should be focused on reducing cardiovascular risk in children and adolescents by promoting a lifestyle of healthy eating and regularly physical exercise. Ultrasound measurement of carotid intima-media thickness is an added factor for an early identification of cardiovascular disease and its evolution in both adult and pediatric population.Introducción: El estudio de la arteria carotídea común mediante ultrasonidos, cada vez cobra mayor importancia para la prevención, tratamiento y evaluación del riesgo de desarrollar enfermedad cardiovascular. Un aumento del índice íntima-media se asocia con la presencia de otros factores cardiovasculares, enfermedad cardiovascular y cerebrovascular y ateroesclerosis en otras zonas del sistema vascular tanto en adultos como en población pediátrica. Material y métodos: Estudio transversal en 202 niños sanos de edades comprendidas entre 4 y 15 años en los que se han valorado parámetros auxológicos, tensión arterial sistólica y diastólica e índice íntima-media carotídea. Resultados: La muestra se compone de 100 varones y 102 mujeres, sin que existan diferencias entre ellos respecto al sexo; se presentan representaciones gráficas de los valores de índice íntima-media carotídea tanto en el total de la muestra como por sexos; existe una correlación positiva entre el índice íntima-media carotídeo con la edad (r = 0,229, p0,05), el peso (r = 0,228, p0,05), la talla (r = 0,265, p0,01) y el IMC (r = 0,212, p0,05). Discusión: La identificación de los factores de riesgo modificables deben ser nuestra prioridad en la práctica clínica diaria. Por ello, en todo programa de salud debe hacerse énfasis en la reducción de riesgo en niños y adolescentes mediante la promoción de un estilo de vida adecuado con alimentación saludable y realización de ejercicio físico de forma regular. La ecografía carotídea y la medida del índice íntima-media es un factor añadido para una identificación precoz de enfermedad cardiovascular y de su evolución tanto en población adulta como pediátrica.

For the diagnosis of patients with growth disorders, visual inspection and the measurement of body segments may provide important information. The most commonly used method is the assessment of the sitting/standing height (SH/SH) ratio and its comparison to aged matched controls.To establish the normal values of the sitting/standing height ratio in a normal Aragonese population from birth to 18 years old.Longitudinal study from birth to 18 years old. Length (up to 3 years old), standing height (as of 2 years old) and sit-ting height were recorded. Percentiles for sitting/ standing height ratio were determined.The study included 165 male children and 167 female children. The values of the sitting/standing height ratio decrease from birth both in males and females (0.656 and 0.647, respectively) until the onset of puberty (0.514 and 0.519); and later start to slightly increase until reaching the definitive adult ratio (0.52 and 0.53, respectively).Sitting/standing height ratio values are presented in normal male and female children up to 18 years old. This ratio decreases from birth to puberty and then slightly increases until reaching the final adult ratio.

BackgroundAryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments.MethodsWe included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at ResultsOverall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas.ConclusionGermline AIPmut occur in 11.7% of patients AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. Design: This study was an international, multicenter, retrospective case collection/database analysis. Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. (J Clin Endocrinol Metab 95: E373-E383, 2010)

Introducción: los supervivientes de leucemia aguda (LA) infantil presentan un riesgo incrementado de alteraciones metabólicas y cardiovascularesque aumentan su morbimortalidad a largo plazo.Objetivo: estimar la prevalencia de obesidad, resistencia a la insulina, dislipemia e hipertensión arterial como factores de riesgo cardiometabólico(FRCM) en un grupo de supervivientes de LA infantil, y analizar las posibles causas asociadas a su desarrollo.Material y métodos: estudio observacional retrospectivo en 47 supervivientes de LA tratados en un periodo de 4 años, que recibieron seguimientodurante 10 años.Resultados: el 40% de los participantes presentaron al menos un FRCM durante el seguimiento, siendo la dislipemia (aumento LDL) el másfrecuente (38,3%), seguido de obesidad/sobrepeso (31,9%) y HTA sistólica (23,4%). El sexo femenino se estableció como factor de riesgo parael desarrollo de todos ellos (RR 1,6; RR 3,16; RR 1,69; p < 0,05). Ningún superviviente desarrolló diabetes mellitus, pero sí resistencia a lainsulina el 19,4%. Los pacientes con leucemias de peor pronóstico presentaron mayor riesgo de desarrollar obesidad, resistencia a la insulinay aumento de LDL (RR 3,56; RR 4,08; RR 2,53; p < 0,05). Los pacientes tratados con trasplante de progenitores hematopoyéticos presentaronmayor riesgo de obesidad, aumento de LDL e HTA sistólica (RR 2,86; RR 2,39; RR 3,12; p