Servicio de endocrinología, Crecimiento y Nutrición del H. Infantil Universitario Niño Jesús / No disponible

Se describe la estructura del Servicio, su personal asistencial, docente e investigador. Sigue una enumeración de su volumen asistencial, los proyectos de investigación aplicada y básica completados y en marcha. Se enumeran los principales trabajos publicados en el último decenio y las tesis doctorales presentadas (AU)

Th estructure of the Department, its care, teaching and investigator personnel are described. Next, a list is given of their care volume and applied and basic research projects, completed and ongoing. The main manuscripts published in the last ten years and PhD theses presented are shown (AU)

Miositis secundaria a tratamiento antitiroideo / Myositis secondary to antithyroid treatment

No disponible

[Familial hypobetalipoproteinemia secondary to a mutation in the apolipoprotein B gene]. / Hipobetalipoproteinemia familiar secundaria a mutación en el gen de la apolipoproteína B.

Familial hypobetalipoproteinemia (FHB) is a rare genetically heterogeneous disorder provoking abnormally low serum levels of apoprotein (apo) B, total cholesterol, and low-density lipoprotein (LDL-C). Patients carrying heterozygous mutations in the APOB (2p24) gene are usually asymptomatic, but homozygous mutations cause clinical disturbances as a result of intestinal fat malabsorption and fat-soluble vitamin deficiency. We present an asymptomatic boy, aged 8 years and 7 months, with low serum levels of apo-B, total cholesterol, triglyceride, LDL-C and very low-density lipoprotein (VLDL-C), as well as vitamin E deficiency. Three asymptomatic relatives also exhibited low apo-B, total cholesterol and LDL-C levels. The APOB (2p24) gene was fully sequenced, demonstrating a heterozygous mutation in exon 26 (G --> T) in all four members of this family. Familial genetic studies in FHB could be useful in the early detection and treatment of homozygous carriers.

Hipobetalipoproteinemia familiar secundaria a mutación en el gen de la apolipoproteína B / Familial hypobetalipoproteinemia secondary to a mutation in the apolipoprotein B gene

La hipobetalipoproteinemia familiar (HBF) es un trastorno infrecuente, con un patrón de herencia heterogéneo, que da origen a valores anormalmente disminuidos de apoproteína (apo) B, colesterol total o lipoproteínas de baja densidad (c-LDL). Los pacientes portadores de mutaciones en el gen APOB (2p24) en heterozigosis suelen ser asintomáticos, pero aquellos que las portan en homozigosis pueden presentar diferentes alteraciones clínicas, debidas a la malabsorción de grasas y deficiencia de vitaminas liposolubles. Se presenta un varón asintomático de 8 años y 7 meses de edad con disminución de los niveles de colesterol total, triglicéridos, c-LDL, lipoproteínas de muy baja densidad (c-VLDL) y apo-B, así como deficiencia de vitamina E. Un total de 3 familiares también asintomáticos presentaron niveles disminuidos de colesterol total, c-LDL y apo-B. La secuenciación del gen APOB demostró, tanto en el paciente como en los 3 familiares afectados, una mutación en heterozigosis en el exón número 26 (G → T). El estudio genético familiar en la HBF puede ser útil para la detección de los portadores homozigotos y la instauración de tratamiento precoz

Familial hypobetalipoproteinemia (FHB) is a rare genetically heterogeneous disorder provoking abnormally low serum levels of apoprotein (apo) B, total cholesterol, and low-density lipoprotein (LDL-C). Patients carrying heterozygous mutations in the APOB (2p24) gene are usually asymptomatic, but homozygous mutations cause clinical disturbances as a result of intestinal fat malabsorption and fat-soluble vitamin deficiency. We present an asymptomatic boy, aged 8 years and 7 months, with low serum levels of apo-B, total cholesterol, triglyceride, LDL-C and very low-density lipoprotein (VLDL-C), as well as vitamin E deficiency. Three asymptomatic relatives also exhibited low apo-B, total cholesterol and LDL-C levels. The APOB (2p24) gene was fully sequenced, demonstrating a heterozygous mutation in exon 26 (G → T) in all four members of this family. Familial genetic studies in FHB could be useful in the early detection and treatment of homozygous carriers

[Diabetes mellitus in children and adolescents: chronic complications and associated diseases]. / Diabetes mellitus en niños y adolescentes: complicaciones crónicas y enfermedades asociadas.

Diabetes is one of the most common chronic diseases. Type 1, or autoimmune, diabetes accounts for more than 95 % of cases in children and adolescents. Chronic hyperglycemia per se is responsible for the development of several microvascular (retinopathy, nephropathy, neuropathy) and macrovascular complications (ischemic heart disease, cerebrovascular disease, and peripheral vascular disease). Other autoimmune diseases are also more frequent in type 1 diabetic patients. The present review aims to provide an update on some recent advances in this field to aid early detection of these complications and prevent or delay their progression through improved metabolic control.

Diabetes mellitus en niños y adolescentes: complicaciones crónicas y enfermedades asociadas / Diabetes mellitus in children and adolescents: Chronic complications and associated diseases

La diabetes mellitus es una de las enfermedades crónicas más frecuentes. En la infancia y la adolescencia, la mayoría de los casos corresponden a diabetes mellitus tipo 1. La hiperglucemia crónica per se es responsable del desarrollo de numerosas complicaciones a largo plazo, tanto microvasculares (retinopatía, nefropatía, neuropatía) como macrovasculares (cardiopatía isquémica, enfermedad cerebrovascular, enfermedad vascular periférica). Por otro lado, la alteración inmune subyacente a la diabetes mellitus tipo 1 es responsable, además, de que los pacientes presenten una mayor incidencia de otras enfermedades autoinmunes. Esta revisión pretende actualizar los conocimientos más recientes en este campo con objeto de detectar precozmente las complicaciones crónicas y las enfermedades asociadas a la diabetes mellitus tipo 1 en la infancia, así como evitar su aparición o enlentecer su progresión mediante un control metabólico adecuado

Diabetes is one of the most common chronic diseases. Type 1, or autoimmune, diabetes accounts for more than 95 % of cases in children and adolescents. Chronic hyperglycemia per se is responsible for the development of several microvascular (retinopathy, nephropathy, neuropathy) and macrovascular complications (ischemic heart disease, cerebrovascular disease, and peripheral vascular disease). Other autoimmune diseases are also more frequent in type 1 diabetic patients. The present review aims to provide an update on some recent advances in this field to aid early detection of these complications and prevent or delay their progression through improved metabolic control

[Triptorelin therapy in girls with central precocious puberty increases body mass index]. / El tratamiento con triptorelina en las niñas con pubertad precoz central provoca incremento del índice de masa corporal.

INTRODUCTION: The most important complications of central precocious puberty (CPP) in girls are loss of height and multiple psychosocial problems. OBJECTIVES: To study the effect of triptorelin therapy in a cohort of girls with CPP. PATIENTS AND METHODS: Thirty-four girls diagnosed with organic or idiopathic CPP and treated with monthly triptorelin were studied. Age, height in standard deviation (SD), bone age (Greulich and Pyle), height prediction (Bayle-Pinneau), body mass index (BMI) in SD, uterine size (pelvic ultrasound), target height, cranial magnetic resonance imaging, triptorelin dose, and treatment duration were studied. RESULTS: Triptorelin produced a statistically significant reduction in growth velocity and an increase in BMI after 1 year of therapy and these changes were maintained after discontinuation of therapy. Adult height in these patients was in accordance with their target genetic height, as well as with their predicted height according to the method of Bayley-Pinneau. No significant differences were found between age of menarche in our patients and in controls. Adult height in patients with organic CPP was significantly lower than that in patients with idiopathic CPP. CONCLUSIONS: 1. Triptorelin can increase BMI in girls with CPP. 2. The presence of an organic cause in patients with CPP worsens the prognosis for adult height. 3. The Bayley-Pinneau prediction method for "average" bone age is useful for establishing a prognosis of adult height in girls with CPP treated with triptorelin.

[Central precocious puberty is associated with a high prevalence of organic disease]. / La pubertad precoz central en niños está asociada a una elevada prevalencia de patología orgánica.

INTRODUCTION: The incidence of central precocious puberty (CPP) is lower in boys than in girls; however, the presence of organic disease is more common in boys. OBJECTIVES: To investigate the percentage of CPP secondary to organic disease in boys and to analyze their clinical and biological characteristics at diagnosis, during follow-up, and at the end of therapy. PATIENTS AND METHODS: Eight boys with a diagnosis of CPP treated with triptorelin every 28 days were included. Age, height in standard deviation (SD), body mass index (BMI) in SD, growth velocity in SD, bone age (Greulich and Pyle), predicted height (Bayle-Pinneau), and target height were analyzed. Testicular volume was measured (according to Prader standards) and peak lutein hormone (LH) values and testosterone levels were determined after gonadotropin-releasing hormone (GnRH) stimulus. RESULTS: Seventy-five percent of the patients with CPP had organic disease. After treatment with triptorelin, growth reduction significantly decreased. In contrast, no changes were seen in the difference between bone age and chronological age, due to the slight difference found at diagnosis. Likewise, during treatment, there was no LH peak and testosterone levels were lower than 0.5 ng/ml in response to GnRH stimulus. No changes were observed in weight or BMI. Three patients reached an adult height similar to their genetic height and their predicted height, as estimated by the Bayle-Pinneau method. CONCLUSIONS: 1. Among boys with CPP we found a substantial number of patients with organic disease. 2. Adult height after treatment with triptorelin can reach the normal range. 3. Determination of testosterone levels can be useful in the follow-up of these children during treatment.

El tratamiento con triptorelina en las niñas con pubertad precoz central provoca incremento del índice de masa corporal / Triptorelin therapy in girls with central precocious puberty increases body mass index

Introducción Las complicaciones más relevantes asociadas a la pubertad precoz central (PPC) en las niñas son una talla adulta baja respecto a la talla genética y desarrollar trastornos psicosociales. Objetivos Estudiar los efectos del tratamiento con triptorelina en un grupo de niñas con PPC. Pacientes y métodos Un total de 34 niñas diagnosticadas de PPC, orgánica o idiopática, tratadas con triptorelina mensual. Se estudian: edad, talla en desviaciones estándar (DE), edad ósea (Greulich y Pyle), predicción de talla (Bayle-Pinneau), índice de masa corporal (IMC) (DE), tamaño uterino (ecografía pélvica), talla diana, resonancia magnética (RM) craneal, así como la dosis de triptorelina y la duración del tratamiento. Resultados El tratamiento con triptorelina produce una disminución de la velocidad de crecimiento y un aumento del IMC a partir del primer año de tratamiento, mantenidos tras la retirada del mismo, de manera estadísticamente significativa. La talla adulta es acorde con la talla genética, y con la predicción de talla mediante el método de Bayley-Pinneau. La menarquia aparece a la misma edad que en la población general. La talla adulta de las pacientes con PPC orgánica es significativamente menor que la de las pacientes con PPC idiopática. Conclusiones 1. El tratamiento de la PPC en niñas con triptorelina puede producir aumento del IMC. 2. La existencia de una causa orgánica de la PPC es un factor que empeora el pronóstico de talla. 3. El método de predicción de talla Bayley-Pinneau, para edad ósea acorde a la edad cronológica es adecuado para hacer un pronóstico de talla final en estas pacientes

Introduction The most important complications of central precocious puberty (CPP) in girls are loss of height and multiple psychosocial problems. Objectives To study the effect of triptorelin therapy in a cohort of girls with CPP. Patients and methods Thirty-four girls diagnosed with organic or idiopathic CPP and treated with monthly triptorelin were studied. Age, height in standard deviation (SD), bone age (Greulich and Pyle), height prediction (Bayle-Pinneau), body mass index (BMI) in SD, uterine size (pelvic ultrasound), target height, cranial magnetic resonance imaging, triptorelin dose, and treatment duration were studied. Results Triptorelin produced a statistically significant reduction in growth velocity and an increase in BMI after 1 year of therapy and these changes were maintained after discontinuation of therapy. Adult height in these patients was in accordance with their target genetic height, as well as with their predicted height according to the method of Bayley-Pinneau. No significant differences were found between age of menarche in our patients and in controls. Adult height in patients with organic CPP was significantly lower than that in patients with idiopathic CPP. Conclusions 1. Triptorelin can increase BMI in girls with CPP. 2. The presence of an organic cause in patients with CPP worsens the prognosis for adult height. 3. The Bayley-Pinneau prediction method for "average" bone age is useful for establishing a prognosis of adult height in girls with CPP treated with triptorelin

La pubertad precoz central en niños está asociada a una elevada prevalencia de patología orgánica / Central precocious puberty is associated with a high prevalence of organic disease

Introducción La incidencia de pubertad precoz central (PPC) en los niños es inferior a la presentada por las niñas; sin embargo, la posibilidad de presentar patología orgánica cerebral es mayor. Objetivos Conocer el porcentaje de PPC secundaria a patología orgánica en niños, y estudiar las características clínico-biológicas al diagnóstico, durante y al final del tratamiento. Pacientes y métodos Se estudian 8 niños diagnosticados de PPC, en tratamiento con triptorelina mensual. Se valoraron: edad, talla en desviaciones estándar (DE), índice de masa corporal (IMC) en DE, velocidad de crecimiento (DE), edad ósea (Greulich y Pyle), predicción de talla (Bayle-Pinneau) y talla diana. Se determinó el volumen testicular, el pico de la hormona luteinizante (LH) tras estimulación con la hormona estimuladora de gonadotropinas (GnRH) y las concentraciones plasmáticas de testosterona. Resultados El 75 % de los niños presentaron patología orgánica. Tras el tratamiento con triptorelina, se evidenció una disminución significativa de la velocidad de crecimiento, sin cambios en la diferencia entre la edad ósea menos la edad cronológica, debido a la escasa diferencia existente al diagnóstico. Durante el tratamiento presentaron un test de GnRH frenado junto con concentraciones de testosterona inferiores a 0,5 ng/ml, sin alteraciones del peso ni del IMC. Tres pacientes alcanzan una talla adulta acorde con su talla genética y con la predicción de talla según el método de Bayley-Pinneau. Conclusiones 1. En niños afectados de PPC el elevado porcentaje de patología orgánica es elevado. 2. La talla adulta tras tratamiento con análogos de GnRH se encontró dentro de la normalidad. 3. La determinación de los niveles de testosterona puede ser de utilidad en el control terapéutico de estos niños

Introduction The incidence of central precocious puberty (CPP) is lower in boys than in girls; however, the presence of organic disease is more common in boys. Objectives To investigate the percentage of CPP secondary to organic disease in boys and to analyze their clinical and biological characteristics at diagnosis, during follow-up, and at the end of therapy. Patients and methods Eight boys with a diagnosis of CPP treated with triptorelin every 28 days were included. Age, height in standard deviation (SD), body mass index (BMI) in SD, growth velocity in SD, bone age (Greulich and Pyle), predicted height (Bayle-Pinneau), and target height were analyzed. Testicular volume was measured (according to Prader standards) and peak lutein hormone (LH) values and testosterone levels were determined after gonadotropin-releasing hormone (GnRH) stimulus. Results Seventy-five percent of the patients with CPP had organic disease. After treatment with triptorelin, growth reduction significantly decreased. In contrast, no changes were seen in the difference between bone age and chronological age, due to the slight difference found at diagnosis. Likewise, during treatment, there was no LH peak and testosterone levels were lower than 0.5 ng/ml in response to GnRH stimulus. No changes were observed in weight or BMI. Three patients reached an adult height similar to their genetic height and their predicted height, as estimated by the Bayle-Pinneau method. Conclusions 1. Among boys with CPP we found a substantial number of patients with organic disease. 2. Adult height after treatment with triptorelin can reach the normal range. 3. Determination of testosterone levels can be useful in the follow-up of these children during treatment

[Transitory neonatal diabetes mellitus and pericentric chromosome 9 inversion]. / Diabetes mellitus neonatal transitoria e inversión pericéntrica del cromosoma 9.

Neonatal diabetes mellitus is an infrequent carbohydrate metabolism disorder with an estimated incidence of approximately one case every 400,000 to 600,000 live newborns. We present the case of a 1-month-old girl with irritability, polyuria, and a 24-h history of eagerness to feed, without fever or other associated symptoms. The patient's karyotype, obtained by amniocentesis, was 46XX with a pericentric chromosome 9 inversion. Her birth weight and length were 2,230 g (-2.65 SD) and 46 cm (-1.8 SD), respectively. Glycemic determinations during the first 72 h of extrauterine life oscillated between 90 and 157 mg/dl. Physical examination revealed general involvement, skin and mucosal pallor, evident signs of dehydration, and impaired awareness. Laboratory tests revealed glycemia: 1552 mg/dL, pH 7.16, pCO2: 23.7 mmHg; bicarbonate: 8.1 mEq/L, base excess: -19.1, and positive ketonemia. After initial stabilization, the patient was treated with intravenous fluids and continuous intravenous regular insulin infusion (initial dose 0.03-0.05 IU/kg/h). After intensive treatment, breast feeding was restored and a short-acting insulin analog was administered subcutaneously after every feed (0.1 to 0.3 IU according to capillary glycemic determinations). Insulin requirements decreased and were discontinued when the infant was 5 months old. Currently, the patient is 2 years and 7 months old and her glycemia and glycosylated hemoglobin levels are normal. Anti-islet (ICA and GAD) and anti-tyrosin phosphatase (IA2) antibodies were absent, as were mutations in the glucokinase gene (GCK).

Diabetes mellitus neonatal transitoria e inversión pericéntrica del cromosoma 9 / Transitory neonatal diabetes mellitus and pericentric chromosome 9 inversion

La diabetes mellitus neonatal es una alteración poco frecuente del metabolismo de los hidratos de carbono. Su incidencia oscila en torno a un caso por cada 400.000 a 600.000 recién nacidos vivos. Se presenta un lactante de un mes de vida con irritabilidad, poliuria y avidez por las tomas de 24 h de evolución, sin fiebre ni otros síntomas. Amniocentesis: cariotipo 46XX con inversión pericéntrica del cromosoma 9. Peso y longitud al nacimiento 2.230 g (­2,65 DE) y 46 cm (­1,8 DE), respectivamente. Destaca la presencia de controles glucémicos entre 90 y 157 mg/dl en las primeras 72 h de vida. Exploración física: mal estado general, palidez cutánea y mucosa, evidentes signos de deshidratación y tendencia al sueño. Análisis complementarios: glucemia: 1.552 mg/dl, pH: 7,16, pCO2: 23,7 mmHg, bicarbonato: 8,1 mEq/l, exceso de bases: ­19,1 y cetonemia positiva. Tras la estabilización inicial, recibió tratamiento con fluidoterapia intravenosa y perfusión intravenosa continua de insulina regular (dosis 0,03-0,05 U/kg/h). Después de este tratamiento intensivo, se restauró la lactancia artificial, junto con la administración de un análogo de insulina de acción rápida, vía subcutánea, tras cada toma (0,1 a 0,3 U/toma, de acuerdo con la glucemia capilar). Progresivamente, disminuyeron las necesidades de insulina hasta prescindir de ella al quinto mes de vida. Actualmente, la paciente tiene una edad de 2 años y 7 meses y presenta concentraciones de glucemia y hemoglobina glucosilada normales. Se demostró la ausencia de anticuerpos frente a las células de los islotes pancreáticos (ICA y GAD) y frente a su enzima tirosín fosfatasa (IA2). Así mismo, se descartó la existencia de mutaciones en el gen codificador de la glucocinasa

Neonatal diabetes mellitus is an infrequent carbohydrate metabolism disorder with an estimated incidence of approximately one case every 400,000 to 600,000 live newborns. We present the case of a 1-month-old girl with irritability, polyuria, and a 24-h history of eagerness to feed, without fever or other associated symptoms. The patient's karyotype, obtained by amniocentesis, was 46XX with a pericentric chromosome 9 inversion. Her birth weight and length were 2,230 g (­2.65 SD) and 46 cm (­1.8 SD), respectively. Glycemic determinations during the first 72 h of extrauterine life oscillated between 90 and 157 mg/dl. Physical examination revealed general involvement, skin and mucosal pallor, evident signs of dehydration, and impaired awareness. Laboratory tests revealed glycemia: 1552 mg/dL, pH 7.16, pCO2: 23.7 mmHg; bicarbonate: 8.1 mEq/L, base excess: ­19.1, and positive ketonemia. After initial stabilization, the patient was treated with intravenous fluids and continuous intravenous regular insulin infusion (initial dose 0.03-0.05 IU/kg/h). After intensive treatment, breast feeding was restored and a short-acting insulin analog was administered subcutaneously after every feed (0.1 to 0.3 IU according to capillary glycemic determinations). Insulin requirements decreased and were discontinued when the infant was 5 months old. Currently, the patient is 2 years and 7 months old and her glycemia and glycosylated hemoglobin levels are normal. Anti-islet (ICA and GAD) and anti-tyrosin phosphatase (IA2) antibodies were absent, as were mutations in the glucokinase gene (GCK)

Adenoma tóxico tiroideo e hipertiroidismo / Toxic thyroid adenoma and hyperthyroidism

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Densidad mineral ósea y composición corporal en la anorexia nerviosa / Bone mineral density and body composition in anorexia nervosa

La anorexia nerviosa (AN) es una enfermedad relativamente frecuente, asociada con pérdida ósea en un elevado número de pacientes y un notable incremento del riesgo de fracturas. En la adolescente con AN puede haber un fallo en alcanzar el pico de masa ósea normal, originando un déficit permanente. Diferentes factores pueden intervenir en esta osteopenia asociada a la AN, incluyendo deprivaciones en calcio y otros macronutrientes, alteraciones en la composición corporal, bajo peso corporal, deficiencia de estrógenos y en algunos casos excesiva actividad física. El objetivo de este trabajo ha sido revisar los factores que intervienen en el desencadenamiento de la pérdida ósea en pacientes con AN

Anorexia nervosa (AN) is a relatively frequent disease, associated with bone loss in a high number of patients and also with increased fracture risk. Adolescent patients can have a failure to achieve bone mass peak with a permanent bone deficit. Different factors can be involved in this AN associated osteopenia, including lack of calcium and other macronutrients, body mass composition alterations, low body weight, estrogen deficiency and in some cases excess physical activity. The objective of this paper has been to review the factors involved in the development of bone loss in patients with AN

Tratamiento con infusión subcutánea continua de insulina en pacientes pediátricos con diabetes mellitus tipo 1 / Treatment with continuous subcutaneous insulin infusion in pediatric patients with type 1 diabetes mellitus

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[Hyperinsulinism-hyperammonemia syndrome due to a de novo mutation in exon 7 (G979A) of the glutamate dehydrogenase gene with excellent response to diazoxide]. / Síndrome de hiperinsulinismo-hiperamoniemia por mutación de novo en el exón 7 (G979A) del gen GLUD-1, con excelente respuesta a diazóxido.

Hyperinsulinism-hyperammonemia syndrome is characterized by recurrent and symptomatic hypoglycemias in childhood, secondary to hyperinsulinism associated with mild and asymptomatic hyperammonemia. This syndrome is caused by dominantly expressed mutations of the glutamate dehydrogenase gene (10q23.3). These mutations modify control of enzyme activity and represent the second cause of congenital hyperinsulinism of known genetic etiology. Moreover, this syndrome is the first genetic disorder due to an increase of function in an enzyme of intermediary metabolism to have been identified. We present the case of a 16-month-old boy with symptomatic recurrent hypoglycemias from the end of the first year of life, caused by a de novo mutation in exon 7 (G979A) of the GDH gene, with excellent outcome after diazoxide treatment.

Síndrome de hiperinsulinismo-hiperamoniemia por mutación de novo en el exón 7 (G979A) del gen GLUD-1, con excelente respuesta a diazóxido / Hyperinsulism-hyperammonemia syndrome due to a de nove mutatuon in exon 7(G979A) del gen GLUD-1, con excelente respuesta a diazóxido

El síndrome de hiperinsulinismo-hiperamoniemia se caracteriza por hipoglucemias sintomáticas recurrentes en la infancia, secundarias a hiperinsulinismo, asociadas a un moderado y asintomático incremento de la amoniemia. Es debido a mutaciones en el gen de la glutamato deshidrogenasa (10q23.3), transmitidas de forma dominante, que alteran el control de la actividad enzimática y representa la segunda causa de hiperinsulinismo congénito de base conocida, siendo la primera enfermedad genética identificada debida a un aumento de la actividad de una enzima del metabolismo intermediario. Presentamos el caso de un niño de 16 meses con hipoglucemias sintomáticas recurrentes desde el final del primer año de vida, debidas a una mutación activadora de novo en el exón 7 (G979A) del gen de la GDH, con excelente respuesta terapéutica a diazóxido (AU)