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Objectives: To analyse the prevalence, evolution of cardiovascular risk factors (CVRF) and their relationship with follow-up of metabolic control in paediatric patients with Type 1 Diabetes (T1DM). Patients and methods: A longitudinal ambispective study was conducted including 75 children and adolescents with T1DM diagnosed from 1996 to 2003 and followed-up for nine years. Family history of CVRF was registered. Data from the second, sixth and ninth year after diagnosis were analysed. Results: Family history of CVRF was found in 46.6% of the patients. The prevalence of HbA1c > 7.5% in the second, sixth and ninth year after diagnosis was 45.3%, 53.3% and 56%, respectively. The prevalence of obesity (BMI > 2SDS) in the three visits was 5.3%, 5.3% and 6.7%, respectively. Hypertension (BP > p90) was found in 14.6%, 8% and 13.3% of the patients in the three visits, respectively. The levels of various parameters were the following: Total cholesterol > 200 mg/dL: 25.3%, 13.3% and 16%; high density cholesterol lipoprotein 100 mg/dL: 38.6%, 34.6% and 38.6%; triglyceride > 150 mg/dL: 0%, 1.3% and 2.6%, respectively. There was a significant increase in the prevalence of TG/HDL-C ≥ 2 between the sixth and the ninth year after diagnosis (1.3% and 9.3%, P 7,5% del 45,3, el 53,3 y el 56%, respectivamente; de obesidad (índice de masa corporal > 2 desviaciones estándar) del 5,3, el 5,3 y el 6,7%, y de HTA (presión arterial > p90) del 14,6, el 8 y el 13,3%. Colesterol total > 200 mg/dl en el 25,3, el 13,3 y el 16%; lipoproteína de alta densidad del colesterol (HDL-c) 100 mg/dl en el 38,6, el 34,6 y el 38,6%; triglicéridos (TG) > 150 mg/dl en el 0, el 1,3 y el 2,6%, respectivamente. Encontramos un aumento significativo en la prevalencia de TG/HDL-c ≥ 2 entre el sexto y el noveno años de evolución de la enfermedad (1,3% y 9,3%, p

Resumen: Objetivos: Analizar la prevalencia, evolución de factores de riesgo cardiovascular (FRCV) y su relación con el control metabólico en pacientes pediátricos con diabetes mellitus tipo 1 (DM1). Pacientes y métodos: Estudio longitudinal ambispectivo en 75 niños y adolescentes españoles con DM1 diagnosticados en los años 1996-2003 y seguidos durante 9 años. Analizamos los FRCV y su evolución al segundo, sexto y noveno años tras el diagnóstico, y los antecedentes familiares (AF) de FRCV. Resultados: El 46,6% tenía AF de FRCV. En el segundo, sexto y noveno años encontramos una prevalencia de HbA1c > 7,5% del 45,3, el 53,3 y el 56%, respectivamente; de obesidad (índice de masa corporal > 2 desviaciones estándar) del 5,3, el 5,3 y el 6,7%, y de HTA (presión arterial > p90) del 14,6, el 8 y el 13,3%. Colesterol total > 200mg/dl en el 25,3, el 13,3 y el 16%; lipoproteína de alta densidad del colesterol (HDL-c) 100 mg/dl en el 38,6, el 34,6 y el 38,6%; triglicéridos (TG) > 150 mg/dl en el 0, el 1,3 y el 2,6%, respectivamente. Encontramos un aumento significativo en la prevalencia de TG/HDL-c ≥ 2 entre el sexto y el noveno años de evolución de la enfermedad (1,3% y 9,3%, p 7.5% in the second, sixth and ninth year after diagnosis was 45.3%, 53.3% y 56%, respectively. The prevalence of obesity (BMI>2SDS) in the three visits was 5.3%, 5.3% y 6.7%, respectively. Hypertension (BP > p90) was found in 14.6%, 8% and 13.3% of the patients in the three visits, respectively. Total cholesterol > 200mg/dl: 25.3%, 13.3% and 16%; high density cholesterol lipoprotein 100mg/dl: 38.6%, 34.6% and 38.6%; triglyceride > 150mg/dl: 0%, 1.3% and 2.6%, respectively. There was a significant increase in the prevalence of TG/HDL-C ≥ 2 between the sixth and the ninth year after diagnosis (1.3% and 9.3%, P

Resumen: Introducción: El tratamiento con radioyodo en la enfermedad de Graves (EG) es una opción terapéutica curativa cada vez más utilizada en niños por encima de 5 años. En Estados Unidos su uso está muy extendido, pero en Europa sigue existiendo controversia respecto a su indicación en la edad pediátrica. Objetivo: Presentar nuestra experiencia con la administración de I131 en la EG en edad pediátrica y analizar su eficacia y seguridad. Pacientes y métodos: Estudio retrospectivo descriptivo de los pacientes pediátricos (< 18 años) diagnosticados de EG en nuestro hospital desde 1982 hasta 2012. Al alcanzar la pubertad, se ofreció una opción curativa a aquellos pacientes que no habían respondido al tratamiento con fármacos antitiroideos (AT). Analizamos las características de los pacientes, niveles de hormona tirotropa, T3 y T4, y autoanticuerpos, respuesta a AT, frecuencia de la remisión de la enfermedad post-I131, aparición de hipotiroidismo y efectos secundarios del I131. Resultados: Desde 1982 hasta 2012 fueron diagnosticados de EG 50 pacientes. Todos recibieron como tratamiento inicial AT, con una duración media 35,3 ± 25,9 meses. Se consiguió remisión permanente en el 46%. Se realizó tiroidectomía a 5 pacientes y se administró I131 a 14 pacientes. La dosis de yodo administrada osciló entre 8,5 y 13 mCi (10,9 ± 1,09). Se obtuvo remisión en el 100%. La tasa de hipotiroidismo permanente fue del 90%. No se observaron progresión de la oftalmopatía ni efectos secundarios en ningún paciente tratado con I131. Conclusiones: El tratamiento con 131I en la EG pediátrica es seguro, lleva a la remisión completa a costa de hipotiroidismo y no exacerba la oftalmopatía. Puede considerarse su utilización en mayores de 5 años cuando no existe respuesta a AT o ante efectos secundarios importantes con esta medicación. Abstract: Introduction: Radioiodine is an important therapeutic option in young patients with Grave's disease (GD). In the United States it is a widespread therapy, but in Europe its use in paediatrics is still controversial. Aim: To report our experience in radioiodine therapy of paediatric GD patients and analyse its effectiveness and safety. Patients and methods: We retrospectively studied our paediatric population (

Resumen: Introducción: La función ejecutiva en población infantil con diabetes es un campo apenas evaluado. Investigarlo puede ayudar a que esta población alcance un pleno rendimiento académico. Este hecho nos ha llevado a estudiar la repercusión que las variables, como la edad de diagnóstico de la diabetes y el nivel de control metabólico, puedan tener en la función ejecutiva de esta población. Pacientes y métodos: Estudiamos a 74 niños: 37 con diabetes tipo 1 (grupo A) y 37 controles (grupo B). El grupo A se dividió en 2 subgrupos, según la edad de diagnóstico: precoz, antes de los 5 años (grupo A1) y tardío, después de los 5 años (grupo A2). Se realizaron comparaciones entre los grupos A y B, y entre los grupos A1 y A2, utilizando el test evaluación neuropsicológica de las funciones ejecutivas en niños (ENFEN). El control metabólico de los 3 meses previos fue valorado mediante la HbA1c. En el momento de la realización del test, se determinó la glucemia capilar. Recogimos el número de hipoglucemias graves registradas en cada paciente. Resultados: Encontramos diferencias en la prueba de interferencias entre los grupos A y B a favor del grupo con diabetes. Entre los grupos A1 y A2 solo encontramos diferencias en las escalas de fluidez fonológica y en el trazado de sendero gris. Las puntuaciones obtenidas son superiores en ambos casos en el grupo A1. Los niveles de HbA1c y de glucemia capilar no guardaban relación con el rendimiento en las distintas pruebas del ENFEN. Ninguno de los pacientes había tenido hipoglucemias graves previas. Conclusiones: 1) Los niños con diabetes tipo 1 obtienen mejores resultados en actividades que requieren resistencia a la interferencia, atención sostenida y control atencional. 2) Los niños con diabetes de comienzo precoz obtienen puntuaciones más altas en tareas de fluidez fonológica y de flexibilidad cognitiva, que los niños con diabetes de comienzo tardío. 3) En nuestro estudio, los niveles de HbA1c y de glucemia capilar no guardan ningún tipo de relación con el rendimiento en las distintas pruebas del ENFEN. Abstract: Introduction: Neurocognitive executive function in the paediatric diabetic population is a rarely studied field. To investigate and improve this aspect could help these patients to reach their full academic potential. This led us to study the impact that variables such as age at diagnosis and adequacy of metabolic control of diabetes may have on the executive cognitive functions of this population. Patients and methods: We studied 74 children: 37 with type 1 diabetes (group A) and 37 without diabetes (group B). Group A was divided into two subgroups, depending on age at diagnosis: early, before 5 years, (group A1) and late, after 5 years, (group A2). We compared group A and B and A1 and A2 groups using the test Neuropsychological assessment of executive functions in children (NAEFC). Diabetes metabolic control was performed by measuring HbA1c and capillary blood glucose before the test. Previous severe hypoglycaemic episodes were recorded. Results: Differences were found among groups A and B in the test of interference. Among the A1 and A2 groups only differences in the scales of phonological fluency and grey trail trace were found. The scores were higher in both cases in the early diabetic group. We did not found any correlation between HbA1c and blood glucose with the different tests of ENFEN results. None of the patients had previous severe hypoglycaemic episodes. Conclusions: 1) Children with diabetes performed better in activities that require resistance to interference, sustained attention and attentional control. 2) Diabetic children with early diagnoses achieved high scores in phonological fluency tasks, and cognitive flexibility. 3) Response to ENFEN was not influenced by HbA1c and blood glucose levels before the test.

Resumen: Introducción: El consenso internacional recomienda el cribado de las alteraciones hidrocarbonadas (AH) en fibrosis quística (FQ) mediante sobrecarga oral de glucosa (SOG) anual desde los 10 años de edad y/o iniciada la pubertad. Objetivos: Evaluar la presencia de AH y su posible repercusión clínica (cambios nutricionales y de función pulmonar) en pacientes impúberes con FQ. Pacientes y métodos: Estudio retrospectivo en 19 pacientes impúberes con FQ (68% varones). Según la SOG, clasificamos (Consenso 2010): tolerancia normal glucosa (TNG) o AH (alteración tolerancia glucosa [ATG], alteración indeterminada glucosa (AIG), diabetes [DRFQ]). Analizamos: SOG (glucemia e insulinemia), estado nutricional (IMC), función pulmonar (espirometría forzada) y función pancreática exocrina. Estudio estadístico con programa SPSS, versión-15.0 mediante pruebas no paramétricas. Resultados: Edad media primera SOG: 8,5 años (5,8-9,8); seguimiento medio: 2 años (2-3). Al inicio: el 53% TNG y el 47% AH; evolutivamente: 4/10 pacientes con TNG desarrollan AH (3ATG, 1DRFQ), 3/4 AIG desarrollan 2ATG y 1DRFQ. Edad media aparición AH: 8,6 años (6,4-11,1). El 69% tuvo deterioro nutricional y/o de la función pulmonar el año previo al diagnóstico de AH. Dos pacientes con AH eran suficientes pancreáticos exocrinos. La insulinemia basal y el área bajo la curva de la SOG fueron comparables entre TNG y AH. El índice insulinogénico fue inferior en AH (p = 0,006). Todos los pacientes tuvieron un pico de secreción de insulina retrasado. Conclusiones: La frecuente detección de AH en pacientes impúberes con FQ y su repercusión clínica plantean la necesidad de adelantar su cribado. La suficiencia pancreática exocrina no excluye el desarrollo de AH. Abstract: Introduction: Annual screening for abnormal glucose tolerance (AGT) with oral glucose test should begin by age 10 years in cystic fibrosis (CF) patients (Consensus-2010). Aims: To examine the frequency of AGT and its outcome in prepubertal CF patients and the changes in glycemic and nutritional status and lung function over the preceding year. Patients and methods: Retrospective study of 19 prepubertal CF patients (68% males). All subjects underwent an oral glucose tolerance test (OGTT). Results were classified as: normal glucose tolerance (NGT) or AGT (impaired glucose tolerance [IGT], CF related diabetes [CFRD] or indeterminate glucose tolerance [INDET]). We analyzed: OGTT (glucose and insulin levels), nutritional status (BMI-SD) and lung function (forced spirometry). Statistical analysis was performed with SPSS program-version-15.0, non parametric tests. Results: Mean age at first OGGT: 8.5 years (5.8-9.8). Mean follow-up: 2 years (2-3). Initially, 47% patients had AGT and 53% NGT. In follow-up: 4/10 NGT patients developed AGT (3 IGT, 1 CFRD). Among initial AGT patients, of 4 INDET: 2 developed IGT, 1 CFRD. Mean age of AGT onset: 8.6 years (6.4-11.1). In 69% AGT patients a declining BMI-DS and/or lung function was found in the preceding year. In OGTTs performed, fasting and 2 h AUC insulin levels were comparable between NGT and AGT; however, insulinogenic index was lower in AGT patients (p=.006). Insulin secretion was delayed in all patients. Conclusions: The high frequency of AGT in prepubertal CF patients and their negative clinical impact supports the usefulness of an earlier glycemic screening.

Resumen: Introducción: Estudiar la prevalencia de esteatosis hepática no alcohólica (EHNA) en una población pediátrica obesa y su relación con parámetros clinicoanalíticos de resistencia a la insulina (RI) y con niveles de adiponectina. Pacientes y métodos: Se estudió a 290 niños (4–18 años) con obesidad. Se analizó el índice de masa corporal (IMC) y la desviación estándar (DE), la acantosis nigricans, la presión arterial, el perfil lipídico, las aminotransferasas y la adiponectina. Se realizó un test de sobrecarga oral de glucosa y se definió la RI mediante el homeostasis model assessment (HOMA) y la esteatosis hepática por ecografía. Definimos el síndrome metabólico (SM) como la presencia de 3 o más de los siguientes criterios: obesidad, hipertensión, hipertrigliceridemia, colesterol ligado a lipoproteínas de alta densidad (cHDL) bajo y alteración hidrocarbonada. Resultados: Cincuenta y dos (18%) pacientes presentaban EHNA en la ecografía, 22 (8%) pacientes tenían elevación de alanin-aminotransferasa (ALT) (≥40U/l). Los pacientes con EHNA fueron significativamente mayores (12,2±2,4 frente a 11,1±2,9 años), más obesos (IMC±DE: 4,5±1,5 frente a 3,8±1,3), y presentaron niveles más elevados de HOMA (3,7±1,5 frente a 2,4±1,4) que los pacientes con ecografía normal. No se encontró diferencia significativa en sexo, raza y estadio puberal. La prevalencia del SM y la acantosis nigricans fue significativamente mayor en los niños con EHNA. Encontramos una correlación inversa entre los niveles séricos de adiponectina y edad, HOMA, ALT y ácido úrico, y encontramos una correlación directa con cHDL. En el análisis de regresión múltiple, las variables que se asociaron de forma independiente con la EHNA fueron IMC±DE, HOMA y adiponectina (odds ratio: 1,4 [1,1-1,9]; 1,3 [1,1-1,6] y 0,9 [0,8-0,9], respectivamente). Conclusiones: La obesidad y la RI son factores de riesgo de la EHNA en niños y adolescentes. Los niveles bajos de adiponectina están fuertemente asociados al desarrollo de EHNA en dichos pacientes. Abstract: Introduction: To study the clinical and laboratory relationships of fatty liver disease in a group of obese children and to investigate whether circulating adiponectin is related to fatty liver disease. Patients and methods: Two hundred-ninety obese patients (age 4–18 years) were studied. Baseline body mass index-standard deviation score (BMI-SDS), acanthosis nigricans, blood pressure, plasma lipids, uric acid, alanine aminotransferase (ALT) and adiponectin were assessed, and a standard oral glucose tolerance test was performed. Insulin resistance (RI) was estimated by the homeostasis model assessment (HOMA) and liver steatosis was assessed by ultrasound (US). Children were classified as having metabolic syndrome if they met three or more of the following criteria: obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol and impaired glucose metabolism. Results: Fifty-two subjects (18%) had fatty liver by US and 22 (8%) had elevated ALT levels (≥40U/L). Subjects with steatosis were significantly older (12.2±2.4 frente a 11.1±2.9yr), heavier (BMI-SDS: 4.5±1.5 frente a 3.8±1.3), and more RI (HOMA: 3.7±1.5 frente a 2.4±1.4), but were comparable in gender, pubertal status and racial distribution to those with normal US. The prevalence of metabolic syndrome and acanthosis nigricans were also higher in the steatosis frente a the normal US group. Serum adiponectin concentration was inversely correlated with age, HOMA, ALT and uric acid and directly correlated with HDL-cholesterol. In a multiple logistic regression analysis, BMI-SDS, HOMA and serum adiponectin, but not age, uric acid or triglycerides, were the covariates independently associated with the presence of steatosis (odds ratio 1.4 [1.1-1.9]; 1.3 [1.1-1.6] and 0.9 [0.8-0.9], respectively). Conclusions: Obesity and RI are risk factors for liver steatosis in children and adolescents. Decreased serum adiponectin is closely and independently associated with steatosis.

Resumen: La enfermedad de Cushing (EC), debida fundamentalmente a un microadenoma hipofisario, es un cuadro clínico poco frecuente en la edad pediátrica y se asocia a una significativa morbilidad. La principal indicación terapéutica es la cirugía transesfenoidal, aunque se reserva el ketoconazol como alternativa terapéutica temporal durante el período de espera previo, a fin de controlar el hipercortisolismo.A continuación se presenta el caso de una niña de 13 años y 8 meses con EC. Sus manifestaciones clínicas eran obesidad, disminución de la velocidad del crecimiento, fenotipo cushingoide, cefaleas e hipertensión arterial. Las determinaciones hormonales pusieron de manifiesto valores elevados de cortisol libre urinario y de corticotropina (ACTH). El ritmo de cortisol y de ACTH así como el test corto y largo de dexametasona confirmaron un hipercortisolismo dependiente de ACTH. La resonancia magnética craneal con gadolinio mostró la presencia de microadenoma en hemiadenohipófisis derecha. El diagnóstico se confirmó tras realizar un cateterismo selectivo de senos petrosos inferiores con estímulo de corticoliberina.En espera de cirugía transesfenoidal, el tratamiento con ketoconazol (200mg/24h) durante 6 meses controló el cuadro de hipercortisolismo. Tras la adenomectomía transesfenoidal, recibió tratamiento sustitutivo con hidrocortisona durante un mes. En la actualidad, la niña lleva 2 años y medio en remisión clínica y hormonal sin cumplir los criterios iniciales posquirúrgicos de curación. Abstract: Cushing's disease (CD), which is caused fundamentally by a pituitary microadenoma, is a rare endocrine disease in the paediatric age and which is associated with significant morbidity. The current treatment of choice for CD is trans-sphenoidal selective adenomectomy resulting in long-term remission rates. Pharmacological management of CD is directed at decreasing adrenal steroid secretion. Ketoconazole inhibits adrenal enzyme activity and decreases cortisol secretion.Our patient is a girl of 13 years and eight months of age with CD. The clinical manifestations were obesity, decrease in growth rate, Cushingoid phenotype, headache and arterial hypertension. The hormone determinations showed elevated values of UFC and ACTH. The circadian rhythm cortisol and ACTH and the short and long dexamethasone tests of provide definitive diagnosis of CD. The cranial MRI with gadolinium suggests the presence of microadenoma in the right pituitary lobe. The diagnosis is confirmed after performing a selective catheterisation of the inferior petrosal sinuses with CRH stimulus.While waiting for trans-sphenoidal surgery, the treatment with ketoconazole (200mg/24h) controlled the hypercortisolism. After the surgical procedure, the patient received replacement therapy with hydrocortisone for 1 month. At the present time, the patient, without fulfilling the post surgery cure criteria, has been 2 and a half years in clinical and hormonal remission.

Resumen: Introducción: las alteraciones hidrocarbonadas (AHC) en fibrosis quística (FQ) suelen ser asintomáticas pero conllevan gran morbilidad. Su diagnóstico precoz puede prevenir el deterioro del estado nutricional y de la función pulmonar (FP). Objetivos: comparar los resultados de la monitorización continua de glucosa (CGMS) con los de la sobrecarga oral de glucosa (SOG) en pacientes con FQ. Evaluar la utilidad de la hemoglobina glicosilada (HbA1c) para el diagnóstico precoz de AHC. Analizar los cambios del estado nutritivo y función pulmonar al diagnóstico de AHC. Pacientes y métodos: en 13 pacientes púberes (7 varones) con FQ y AHC, diagnosticada por SOG, implantamos CGMS. Analizamos: edad, sexo, mutación relacionada con FQ, insuficiencia pancreática exocrina, HbA1c (%), glucemia en ayunas y 2h tras SOG. En el CGMS valoramos: glucosa global, en ayunas y posprandial, y excursiones de glucosa >140mg/dl. Además, comparamos el estado nutricional (índice de masa corporal) y la FP (capacidad vital forzada y volumen espiratorio forzado en el primer segundo) en ese momento y en el año previo. Resultados: media de edad al diagnóstico de AHC de 16,4 años (11-22); 11 pacientes tenían mutación ΔF508. Todos tenían insuficiencia pancreática exocrina. Cumplían criterios de diabetes 1/13 con SOG y 7/13 (53,8%) con CGMS. Se evidenció una declinación del estado nutricional y/o de la FP en el 77%. Sólo 4 pacientes tenían HbA1c patológica. Conclusiones: el CGMS detecta mejor la diabetes relacionada con FQ que la SOG. La presencia de AHC tiende a relacionarse con un empeoramiento nutricional y/o de FP. La HbA1c no permite el diagnóstico precoz de AHC en FQ. Abstract: Background: Diabetes mellitus (DM) is an increasing complication of cystic fibrosis (CF). It is associated with enhance morbidity. Continuous glucose monitoring system (CGMS) could detect glucose disorders earlier than other screening tests usually used. Aims: To compare oral glucose tolerance test (OGTT), HbA1c and CGMS in patients with CF and recent disorders of glucose homeostasis and to analyse changes in nutritional status and/or pulmonary function. Patients and methods: Thirteen patients with CF (11–22 years, 7 males) were studied using OGTT, HbA1c and CGMS. All of them had newly diagnosed glucose disturbances. They were not receiving steroid therapy or had an underlying illness. In all subjects we compared: HbA1c levels (%), fasting and 2-hours glucose OGTT (mg/dl) and glucose CGMS values (overall, fasting, 2-hours post mean-meals and excursions >140mg/dl at any time). Furthermore, body mass index, forced expiratory volume in the first second (%) and forced vital capacity (%) were evaluated in the previous year and at the time of the study. We also analysed exocrine pancreatic function and CF-mutation. Results: Mean age at diagnosis of glucose disturbance was 16.4 years. All patients had insufficient exocrine pancreatic function and 11/13 presented ΔF508 CF-mutation. Only one patient was diagnosed with DM using OGGT and 7/13 (53.8%) with CGMS. A total 77% of patients had poor nutritional status and/or pulmonary function at time of diagnosing the glucose disorder. Only 4 patients had abnormal HbA1c levels. Conclusions: CGMS allows a better detection of glucose disorders than OGTT. Glucose homeostasis abnormalities are associated with a decrease in nutritional status and/or pulmonary function. HbA1c does not aid in the early diagnose of glucose disorders.

Objetivo: Determinar la prevalencia de enfermedad celíaca (EC) en pacientes pediátricos con diabetes tipo 1 (DM-1) y evaluar la repercusión de la retirada del gluten de la dieta en el crecimiento y el control metabólico. Pacientes y métodos: Estudio retrospectivo de 261 pacientes pediátricos con DM-1. El diagnóstico de EC se basó en la presencia de anticuerpos antiendomisio y transglutaminasa junto con la confirmación mediante biopsia intestinal. Valoramos el impacto de la retirada del gluten sobre el control metabólico (medias anuales de hemoglobina glucosilada [HbA1c]), el crecimiento (talla y velocidad de crecimiento anual) y el estado nutritivo (índice de masa corporal [IMC]). Comparamos los pacientes diagnosticados de DM y EC después del diagnóstico de la diabetes con un grupo control de pacientes afectados exclusivamente de DM-1. Resultados: Un total de 21 de los 261 pacientes (8 %) presentaban EC. El 19 % de ellos tenían otro tipo de autoinmunidad asociada. No evidenciamos diferencias significativas en cuanto al crecimiento y al grado de control metabólico de la diabetes tras la retirada del gluten. Conclusiones: Encontramos una alta incidencia de EC en nuestra población con DM-1. El cribado de EC no repercute en el control metabólico de la diabetes ni en el desarrollo pondero-estatural. A pesar de ello, y debido a la alta incidencia de EC en España y a la posibilidad de aparición de complicaciones a largo plazo, como la osteoporosis y los linfomas, recomendamos realizar cribado sistemático en todos los pacientes diagnosticados de DM-1, fundamentalmente, en los primeros 5 años tras el diagnóstico. : Objective: To asses the prevalence of celiac disease and to evaluate the clinical effects of a gluten-free diet on metabolic control and growth in children and adolescents with type 1 diabetes mellitus (DM1). Patients and methods: We performed a retrospective study of 261 patients with DM1. Diagnosis of celiac disease was based on the presence of endomysium and tissue transglutaminase antibodies in serum and was confirmed by intestinal biopsy. The impact of a gluten-free diet on metabolic control (mean annual HbAlc values), growth (height and annual growth velocity) and nutritional status (body mass index) was evaluated. Patients diagnosed with DM1 and subsequently with celiac disease were compared with a control group of patients with DM1 only. Results: Twenty-one (8 %) of the 261 diabetic patients were diagnosed with celiac disease and 19 % also had another associated autoimmune disease. No significant differences were found in growth or metabolic control after withdrawal of gluten from the diet. Conclusions: We found a high prevalence of celiac disease in our type 1 diabetes population. A gluten-free diet had no effects on metabolic control of diabetes or on height or weight. Nevertheless, given the high prevalence of celiac disease and the possible development of long-term complications, such as lymphoma and osteoporosis, we recommend systematic screening in all diabetic patients, especially in the first 5 years after diagnosis of DM1.

Introducción: El propósito del estudio es determinar la eficacia y la seguridad del tratamiento con bombas de infusión subcutánea continua de insulina en un grupo de niños y adolescents con diabetes mellitus tipo 1. Pacientes y métodos: Se analizan los datos de 17 pacientes diabéticos tratados en nuestra Unidad de Diabetes Pediátrica durante el primer año de terapia con bomba de infusión subcutánea continua de insulina. Comparamos la HbA1c, índice de masa corporal, dosis de insulina, episodios de hipoglucemia grave y episodios de cetoacidosis antes y después del inicio de la terapia con bomba de insulina. Resultados: La media de edad fue de 14,02 ± 3,70 años y el tiempo medio de evolución de la diabetes de 5,81 ± 3,31 años. Se objetiva una disminución de HbA1c de 8,12 ± 1,46 a 7,52 ± 0,87 % a los 2 meses de tratamiento que se mantiene en estas concentraciones durante todo el año. La dosis de insulina disminuye de 0,99 ± 0,24 a 0,84 ± 0,18 U/kg/día al año de tratamiento. El índice de masa corporal permanence estable. También se observa una disminución del número de episodios de hipoglucemia grave (0,47 ± 1,23 episodios/ paciente en los 6 meses previos al inicio del tratamiento con bomba, 0,29 ± 1,20 durante los primeros 6 meses de la nueva terapia y 0,06 ± 0,24 de los 6 a 12 meses). Hubo tres episodios de cetoacidosis, todos ellos en el mismo paciente. Conclusiones: La terapia con bomba de infusión subcutánea continua de insulina es una alternativa eficaz y segura para tratar niños y adolescentes con diabetes mellitus tipo 1, ya que permite mejorar el control metabólico con disminución del riesgo de hipoglucemia grave. : Introduction: To determine the efficacy and safety of continuous subcutaneous insulin infusion therapy in a group of children and adolescents with type 1 diabetes mellitus. Patients and methods: Data from 17 patients were collected during the first year of continuous subcutaneous insulin infusion treatment. All patients were followed-up at our diabetic pediatric clinic. HbA1c, body mass index, insulin dose, severe hypoglycemic episodes, and diabetic ketoacidosis events before and after initiation of pump therapy were compared. Results: The mean age was 14.02 ± 3.70 years and the mean diabetes duration was 5.81 ± 3.31 years. HbA1c decreased from 8.12 ± 1.46 to 7.52 ± 0.87 % after 2 months of therapy and this decrease was maintained throughout the first year of continuous subcutaneous insulin infusion treatment. Insulin dose decreased from 0.99 ± 0.24 to 0.84 ± 0.18 U/kg/day after 1 year of treatment. Body mass index remained unchanged. There were fewer severe hypoglycemic events after the start of insulin pump therapy (0.47 ± 1.23 events/patient in the 6 months before continuous insulin infusion, 0.29 ± 1.20 episodes in the first 6 months of insulin pump therapy and 0.06 ± 0.24 in the period from 6 to 12 months of the treatment). There were 3 ketoacidosis episodes, all in the same patient. Conclusions: Continuous subcutaneous insulin infusion is a safe and effective alternative in the treatment of children and adolescents with type 1 diabetes mellitus. It improves metabolic control and decreases the number of severe hypoglycemic episodes.

Introducción: La enfermedad de Graves-Basedow, que es la causa más frecuente de hipertiroidismo en la edad pediátrica, es muy infrecuente en el niño preescolar. Se describen los casos de 4 niñas menores de 6 años de un total de 30 pacientes diagnosticados de enfermedad de Graves-Basedow entre 1985 y 2004. El motivo del estudio fue taquicardia, diarrea, retraso del lenguaje y estudio fortuito por alteraciones ecográficas tiroideas. La talla y la maduración ósea estaban avanzadas en 3 de las 4 pacientes. El bocio estuvo ausente o fue de muy pequeño tamaño, y en ningún caso existió oftalmopatía. Todas presentaron elevación de T4 y T3 con hormona tiroestimulante (TSH) suprimida y en 3 casos los anticuerpos estimulantes del tiroides fueron positivos (en el caso más antiguo la técnica no estaba disponible). Dos de las pacientes están curadas tras 5 años de tratamiento con carbimazol, y las otras dos están aún en tratamiento, sin haberse evidenciado ningún efecto secundario. : Introduction: Graves’ disease, which is the main cause of hyperthyroidism in the pediatric age group, is very rare in pre-school children. We describe the cases of four girls, aged less than 6 years old, out of a total of 30 patients diagnosed with Graves’ disease between 1985 and 2004. Investigations were motivated by tachycardia, chronic diarrhea, language development delay or thyroid nodules detected by cervical ultrasonography. In three of the four patients height and bone age were advanced. In all patients goiter was small or absent. None of the patients had ophthalmic disease. In all patients free T3 and T4 were elevated and thyroid-stimulating hormone was suppressed. Three patients were positive for thyroid-stimulating immunoglobulins (the method was not available for the oldest case). Two patients showed complete resolution after 5 years of treatment with carbimazole. The remaining two patients are still under treatment and no adverse effects have been documented.

To analyse the prevalence, evolution of cardiovascular risk factors (CVRF) and their relationship with follow-up of metabolic control in pediatric patients with Type 1 Diabetes (T1DM).Longitudinal ambispective study including 75 children and adolescents with T1DM diagnosed from 1996 to 2003 and followed-up for nine years. Family history of CVRF was registered. Data from the second, sixth and ninth year after diagnosis were analysed.Family history of CVRF was found in 46.6% of the patients. The prevalence of HbA1c7.5% in the second, sixth and ninth year after diagnosis was 45.3%, 53.3% y 56%, respectively. The prevalence of obesity (BMI2SDS) in the three visits was 5.3%, 5.3% y 6.7%, respectively. Hypertension (BPp90) was found in 14.6%, 8% and 13.3% of the patients in the three visits, respectively. Total cholesterol200mg/dl: 25.3%, 13.3% and 16%; high density cholesterol lipoprotein40 mg/dl: 1.3%, 1.3% and 4%; low density cholesterol lipoprotein100mg/dl: 38.6%, 34.6% and 38.6%; triglyceride150 mg/dl: 0%, 1.3% and 2.6%, respectively. There was a significant increase in the prevalence of TG/HDL-C ≥ 2 between the sixth and the ninth year after diagnosis (1.3% and 9.3%, P.05). A persistent HbA1c ≥ 7.5% showed a statistically significant relationship to a 0.94 decrease in HDL-C z-score between the second and the sixth year, and a persistent HbA1c7.5% was significantly associated with a 0.55 increase in HDL-C z-score (P=.015) in the same period.A non-optimal metabolic control in first years of DM1 is associated with a decrease in HDL-C z-score. TG/HDL-C ratio could be an early marker of cardiovascular risk.

Objetivos: Evaluar el impacto sobre la función gonadal del trasplante de médula ósea realizado durante la infancia. métodos: Estudiamos la función gonadal en 19 pacientes pospuberales (13 varones y 6 mujeres) de 12,6 a 20 años de edad, 2 a 9 años después de haber sido sometidos a trasplante de médula ósea por distintas enfermedades. Quince pacientes habían recibido tratamiento quimioterápico previo y 6 pacientes radioterapia craneal; 11 pacientes recibieron radioterapia corporal total durante el acondicionamiento. Se caracterizaron los estadios de Tanner de desarrollo puberal y se midieron el volumen testicular en los varones (orquidómetro de Prader) y las concentraciones séricas de LH, FSH, testosterona y 17-beta-estradiol. Resultados: Doce pacientes presentaron disfunción gonadal primaria. Tres de ellos no habían recibido radioterapia corporal total. Conclusiones: Los resultados obtenidos demuestran que la disfunción gonadal es una secuela frecuente en los niños sometidos a trasplante de médula ósea; el daño puede ser atribuido tanto a la quimioterapia como a la radioterapia, sin poder excluir un efecto sinérgico de ambas. El hecho de que el trasplante tuviera lugar en la etapa prepuberal no puede considerarse en nuestra serie como un factor protector frente al daño gonadal inducido por quimioterapia o radioterapia. : Objective: To evaluate the effect of bone marrow transplantation during childhood on gonadal function in postpubertal patients. Procedure: We studied 19 post-pubertal patients (13 males, 6 females) aged 13-20 years, 2-9 years after bone marrow transplantation for diverse diseases. Fifteen patients had received multi-agent cytotoxic treatment and 6 had received cranial irradiation prior to transplantation; eleven patients received total body irradiation. Gonadal function was assessed by typifying Tanner's stages of pubertal development and by measuring testicular volume in males (Prader's orchidometer). Serum concentrations of lutei-nizing hormone, follicle-stimulating hormone, testosterone and 17-beta-estradiol were also measured. Results: Twelve patients were found to have gonadal dysfunction of gonadal origin. Of these, three had not received total body irradiation. Conclusions: The results obtained show that gonadal dysfunction is frequent in patients treated with bone marrow transplantation. This damage can be attributed to both chemo-and radiotherapy but a synergistic effect between these treatments could not be excluded. The prepubertal status of patients at the moment of transplantation was not a protective factor against chemo- or radiotherapy-induced gonadal damage in our series.

Fundamento: El análogo de la insulina humana Lispro (Lys B28, ProB29) remeda mejor el perfil de la respuesta normal de la insulina pancreática ante la ingestión por lo que puede ser una alternativa en el tratamiento clásico de la diabetes tipo 1 en la infancia. El objetivo ha sido analizar la respuesta a una pauta de tratamiento insulínico con este análogo, tras un año de seguimiento. Pacientes y métodos: Veinte pacientes diabéticos puberales, 9 varones y 11mujeres, con una edad media de 15,6 años (desviación estándar [DE], ± 4,5) y un tiempo medio de evolución de la enfermedad de 8,3 años (± 4,3), cambiaron su tratamiento intensivo clásico, mezcla de insulina regular (HR) e insulina NPH (Humulina NPH) por una nueva pauta con insulina Lispro e insulina NPH en 3 o 4 dosis. Todos los pacientes habían recibido educación diabetológica y se realizaban 4 o más glucemias capilares al día y autocontrol. Analizamos los 6 meses previos (grupo A) y los 12 meses posteriores al cambio de tratamiento (grupo B) y comparamos la cantidad de insulina (U/kg/día), la proporción de insulina rápida e intermedia en cada dosis, las modificaciones en la dieta, el grado de control metabóli-co valorado mediante la media de las Ab A1c realizadascada 2 meses, la presencia de hipoglucemias graves y elgrado de satisfacción de los pacientes con el tratamiento. Resultados: El número de dosis administradas, así como la cantidad de insulina al día, fue igual en ambos grupos (3,7 [± 0,6] dosis/día; 0,9 [± 0,2] U/kg/día).En la pauta con Lispro disminuyó la proporción de insulina rápida/insulina intermedia. Esta diferencia fue estadísticamente significativa en la dosis antes del desayu-no (clásico, 65,4 ± 30% frente a Lispro, 47,1 ± 19,6%), y en la dosis antes de la comida (clásico, 58,1 ± 29,3% frente a Lispro, 39 ± 12,8%). La mayoría de los pacientes no precisaron la ingestión de media mañana y merienda. No hu-bo modificaciones en el índice de masa corporal.Aunque el control metabólico mejoró ligeramente (clásico, -X Hb A1c = 7 ± 1,2 frente a Lispro -X Hb A1c = 6,6 ±1,1), la diferencia no fue estadísticamente significativa. Tres pacientes tuvieron un episodio de hipoglucemia grave en los primeros 6 meses de tratamiento con la nueva pauta. Todos estuvieron satisfechos con la nueva insulina. Conclusiones: La terapia intensiva con insulina Lispro en combinación con dosis adecuadas de insulina basal (NPH) puede ser una buena alternativa en el tratamiento de pacientes diabéticos adolescentes. : Background: The human insulin analogue, Lispro (Lys B28, Pro B29), is more similar to normal pancreatic insulin response to ingestion. Therefore, it could provide an alternative to the classical treatment of type-1 diabetes in childhood. The aim of this study was to analyze the response to insulin treatment with this analogue during 1 year. Patients and methods: In a study group of twenty puberal diabetic patients (nine male and 11 female) with a mean age of 15.6 years (± SD) and with diabetes of a mean of 8.3 years (± 4.3 SD), classical intensive treatment, a combination of regular in-sulin (HR) and NPH insulin (Humulin NPH) was substituted for a new treatment with Lispro and NPH insulin in 3-4 doses. All patients had received diabetic education and performed at least four blood glucose tests daily and self monitoring. We analyzed the 6 months prior to the change in treatment (Group A) and the 12 months after the change (Group B). The amount of insulin (u/kg/day), thefast/intermediate insulin ratio in each dose, dietary modifications, the level of metabolic control given by the HbA1C average measured every 2 months, severe hypoglycemia and the patient’s level of satisfaction with the new treatment were compared between the two groups. Results: The number of daily doses, as well as the daily insulin intake, was the same in both groups (3.7 [± 0.6] doses/day; 0.9 [± 0.2] u/kg/day). With Lispro treatment the ratio fast/intermediate insulin was reduced. This reduction was statistically significant for the pre-breakfast dose (Classical = 65.4 ± 30% vs Lispro = 47.1 ± 19.6%), and for the pre-lunch dose (Classical = 58.1 ± 29.3% vs Lispro = 39 ± 12.8%). Most patients did not need neither mid-morning or mid-afternoon doses. There were no modifi-cations in body mass index. Although metabolic control im-proved slightly (Classical X-AbA1c= 7 ± 1.2 vs Lispro X-AbA1c= 6.6 ± 1.1), the difference was not statistically significant. Three patients had a severe hypoglycemic episode in the first 6 months with the new treatment pattern. All of them were satisfied with the new insulin. Conclusions: Intensive therapy with Lispro insulin combined with appropriate doses of basal insulin (NPH) can provide a good alternative in the treatment of diabetic teenagers.

La alteración del metabolismo hidrocarbonado es una complicación frecuente de la fibrosis quística. La diabetes relacionada con fibrosis quística (DRFQ) se debe a una disminución en la secreción de la insulina secundaria a la insuficiencia pancreática. Los pacientes con fibrosis quística y diabetes presentan mayor morbilidad y mortalidad y el mismo riesgo de las complicaciones crónicas de la diabetes que los pacientes con diabetes tipo 1o 2.El diagnóstico precoz y el tratamiento adecuado de la diabetes de estos pacientes es imprescindible.En mayo de 2000 tuvo lugar en Madrid una conferencia de consenso sobre DRFQ para definir las pautas para su diagnóstico y tratamiento. : Abnormal glucose tolerance and diabetes mellitus are a common complication of cystic fibrosis (CF). Cystic fibrosis related diabetes (CFRD) is due to decreased insulin secretion, secondary to pancreatic insufficiency. Patients with CFRD have increased morbidity and mortality and are subject to the same microvascular complications as patients with other types of diabetes. Prompt diagnosis and aggressive management of CFRD is important.A consensus conference on CFRD was held in Madrid in May 2000 to define the current standards for the diagnosis and management of this disease in Spain.

El mosaicismo 45,X/46,XY tiene una amplia expresividad clínica. El 90 % de los casos de diagnóstico prenatal son varones fenotípicamente normales, mientras que los casos de diagnóstico posnatal engloban un amplio espectro clínico que incluye síndrome de Turner, disgenesia gonadal mixta, seudohermafroditismo masculino y varones aparentemente normales. Se indican los hallazgos clínicos, endocrinológicos, citogenéticos e histológicos de 3 pacientes con fenotipo masculino normal y mosaicismo 45,X/46,XY de diagnóstico posnatal durante su estudio por talla baja. Sólo uno de los pacientes presentaba rasgos turnerianos. No se ha encontrado correlación entre la proporción de líneas celulares 45,X y 46,XY en sangre, gónadas y fenotipo. La posibilidad de desarrollar complicaciones como disgenesia del tejido gonadal con riesgo de malignización e infertilidad y talla baja susceptible de beneficiarse del tratamiento con hormona de crecimiento implica la necesidad de un seguimiento estrecho sobre todo en aquellos pacientes de diagnóstico prenatal y posnatal con fenotipo normal. : There is wide variation in the clinical expression of 45,X/46,XY mosaicism. Ninety percent of prenatally diagnosed boys have normal male phenotype at birth, while those diagnosed postnatally show a wide spectrum of phenotypes, ranging from Turner syndrome, mixed gonadal dysgenesis, and male pseudohermaphroditism to apparent normality.We report the clinical, cytogenetic, endocrinologic and histologic findings in three boys with an apparently normal male phenotype and 45,X/46,XY mosaicism who were diagnosed postnatally because of their short stature. With the exception of one patient with Turner stigmata, no other abnormal features were found.No correlation between the proportion of 45,X/46,XY cell lines in blood, gonads and phenotype was found. Both prenatally and postnatally diagnosed boys with normal male phenotype must be followed-up because they can develop late-onset abnormalities, such as dysgenetic testes leading to infertility or neoplastic transformation, and short stature, which could be improved with growth hormone therapy.

El interferon-α es el principal agente terapeutico en los pacientes con hepatopatia cronica activa por el virus de la hepatitis C. Las alteraciones tiroideas autoinmunitarias constituyen un efecto secundario frecuente y bien conocido del tratamiento con interferon-α. Presentamos el caso de una paciente con hepatitis C cronica postrasfusional tratada con interferon-α en 2 ocasiones con un intervalo de 7 anos. La paciente presento, tras el primer ciclo de tratamiento con interferon-α, tirotoxicosis por enfermedad de Graves con recurrencia en 2 ocasiones. Despues del segundo ciclo de tratamiento, la paciente presento hipotiroidismo primario autoinmunitario.

Resumen: El tratamiento intensivo de la diabetes mellitus tipo 1 (DM1) permite retrasar y enlentecer la progresión de las complicaciones crónicas (DCCT 1993).Este tipo de tratamiento en niños y adolescentes con DM1 tiene una complejidad diferente de la de otras etapas de la vida y por ello se necesitan Unidades de Asistencia Especializada en diabetes pediátrica. Se valoran los diferentes documentos y declaraciones sobre los derechos de los pacientes con DM1 y se enfatiza la necesidad de una adecuada asistencia sanitaria.En la última década, se han desarrollado en Europa varios proyectos para establecer una evaluación comparativa del tratamiento de la DM en edad pediátrica con el objetivo de establecer centros hospitalarios con una asistencia muy cualificada en su control.El Grupo de trabajo de Diabetes de la Sociedad Española de Endocrinología Pediátrica ha elaborado este documento con el objetivo de obtener un Consenso Nacional para la asistencia al niño y adolescente con DM1 en «Unidades de Referencia en diabetes pediátrica» y, a su vez, poder asesorar a las administraciones para establecer una Red Nacional dirigida a la asistencia del niño y adolescente con DM y organizar las Unidades de Atención Integral de la diabetes pediátrica en hospitales con nivel de referencia por su calidad asistencial. Abstract: Intensive treatment of type 1 diabetes mellitus (DM1) delays and slows down the progression of chronic diabetes complications (DCCT 1993).This type of treatment in children and adolescents with DM1 has a different complexity to other stages of life and therefore, needs specialized care units. Various documents and declarations of diabetic patient's rights are evaluated, and the need for an adequate health care is emphasized.In the last decade, several projects have been developed in Europe to create a benchmark treatment of pediatric diabetes, with the aim of establishing hospitals with highly qualified healthcare to control it.The Diabetes Working Group of the Spanish Society for Pediatric Endocrinology (SEEP) has prepared this document in order to obtain a national consensus for the care of children and adolescents with type 1 diabetes in specialist Pediatric Diabetes Units, and at the same time advise Health Care Administrators to establish a national healthcare network for children and adolescents with diabetes mellitus, and organize comprehensive pediatric diabetes care units in hospitals with a reference level in quality of care.

Intensive treatment of type 1 diabetes mellitus (DM1) delays and slows down the progression of chronic diabetes complications (DCCT 1993). This type of treatment in children and adolescents with DM1 has a different complexity to other stages of life and therefore, needs specialized care units. Various documents and declarations of diabetic patient's rights are evaluated, and the need for an adequate health care is emphasized. In the last decade, several projects have been developed in Europe to create a benchmark treatment of pediatric diabetes, with the aim of establishing hospitals with highly qualified healthcare to control it. The Diabetes Working Group of the Spanish Society for Pediatric Endocrinology (SEEP) has prepared this document in order to obtain a national consensus for the care of children and adolescents with type 1 diabetes in specialist Pediatric Diabetes Units, and at the same time advise Health Care Administrators to establish a national healthcare network for children and adolescents with diabetes mellitus, and organize comprehensive pediatric diabetes care units in hospitals with a reference level in quality of care.

DKA at diagnosis of T1DM is a life-threatening situation that represents the main cause of morbidity and mortality in pediatric patients with T1DM.To determine whether the occurrence and severity of DKA at diagnosis of T1DM has suffered any changes in recent years in the Spanish paediatric population.Data from 1169 patients with T1DM under 15 years of age was retrospectively studied (2004 -2008) for the presence and severity of DKA at the onset of T1DM, and compared to previous available studies in Spain. This study is multicentric, nationwide with eleven major Paediatric Diabetes Units involved.Complete data were available from 1151 patients (98%). Frequency of DKA was 39.5%, which is not significantly different from previous Spanish studies. 33.8%, children of 0-4.9 years of age, 40.8% aged 5-10.9 and 25.2% aged 11-14.9 years. Mean age of patients with DKA was significantly lower than the one of patients without DKA (7.44 +/- 4.10 versus 8.47 +/- 3.63 years). Mild DKA was occurring more frequently than moderate and severe forms (47.8%, versus 34.4% versus 17.8%, p0.0001). Incidence of severe DKA was significantly higher in children under 4.9 years of age, especially in those younger than 2 years (p0.001). Severe DKA led to complications in three children (cerebral oedema [n=1]), cerebral infarction (n=1) and femoral vein thrombosis (n=1).Frequency of DKA at diagnosis of T1DM in Spain is still high although most cases were mild. Children under 2 years of age seem to be at increased risk for severe DKA.

Obesity in children is becoming more prevalent. Obesity and type 2 diabetes is higher in the Latin American immigrant population.To analyze the influence of ethnicity on the prevalence of metabolic syndrome (MS) and its components in an obese pediatric population.A retrospective study of 616 obese children and adolescents (BMI ≥2 SD [Hernández 88-04]), was conducted on 142 Latin American children and 474 Caucasians, which compared the prevalence of metabolic syndrome and its components according to modified Cook criteria (2003): obesity+2 or more of the following components: HDL-cholesterol40mg/dl, triglycerides110mg/dl, systolic and/or diastolic blood pressurep90 (Task Force 2004), and impaired glucose metabolism (ADA 2011). Hepatic function, family history of MS, HbA1c, insulin resistance (HOMA) and BMI evolution at one year of treatment with changes in lifestyle (diet and exercise) were also assessed.Almost one-third (30.5%) of Latin American children had MS compared to 15.5% of Caucasians (OR=2.4 [CI 95%: 1.5-3.8]), P.005] and OR=2.5 adjusting for sex, SD-BMI and puberty. Latin American children also had a higher insulin resistance (58.6% vs 42.8%, P.005) and a worse outcome after one year of treatment.There is a higher prevalence of MS in our Latin American obese pediatric population with poor adherence to the measures of change in lifestyle, making these patients a group with potentially increased risks of cardiovascular disease in adulthood.

Annual screening for abnormal glucose tolerance (AGT) with oral glucose test should begin by age 10 years in cystic fibrosis (CF) patients (Consensus-2010).To examine the frequency of AGT and its outcome in prepubertal CF patients and the changes in glycemic and nutritional status and lung function over the preceding year.Retrospective study of 19 prepubertal CF patients (68% males). All subjects underwent an oral glucose tolerance test (OGTT). Results were classified as: normal glucose tolerance (NGT) or AGT (impaired glucose tolerance [IGT], CF related diabetes [CFRD] or indeterminate glucose tolerance [INDET]). We analyzed: OGTT (glucose and insulin levels), nutritional status (BMI-SD) and lung function (forced spirometry). Statistical analysis was performed with SPSS program-version-15.0, non parametric tests.Mean age at first OGGT: 8.5 years (5.8-9.8). Mean follow-up: 2 years (2-3). Initially, 47% patients had AGT and 53% NGT. In follow-up: 4/10 NGT patients developed AGT (3 IGT, 1 CFRD). Among initial AGT patients, of 4 INDET: 2 developed IGT, 1 CFRD. Mean age of AGT onset: 8.6 years (6.4-11.1). In 69% AGT patients a declining BMI-DS and/or lung function was found in the preceding year. In OGTTs performed, fasting and 2h AUC insulin levels were comparable between NGT and AGT; however, insulinogenic index was lower in AGT patients (p=.006). Insulin secretion was delayed in all patients.The high frequency of AGT in prepubertal CF patients and their negative clinical impact supports the usefulness of an earlier glycemic screening.

Glucose monitoring methods have made great advances in the last decade with the appearance of the continuous glucose monitoring systems (CGMS) that measure the glucose levels in the interstitial liquid, providing information about glucose patterns and trends, but do not replace the self-monitoring of capillary glucose. Improvement in diabetes control using the CGMS depends on the motivation and training received by the patient and family and on the continuity in its use. Due to the development and widespread use of these systems in clinical practice, the diabetes group of the Sociedad Española de Endocrinología Pediátrica has drafted a document of consensus for their indication and use in children and adolescents. Only a limited number of trials have been performed in children and adolescent populations. More data are needed on the use of this technology in order to define the impact on metabolic control.

This article reports on the Spanish Position Statement for the Diabetes Pediátric Group for the Spanish Pediatric Endocrinology Society (SEEP) on continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes. The practical issues about their indications, appropriate candidates, feasibility, and limits are outlined. The conclusions are based on the comprehensive review and balanced assessment of the evidence base on the international consensus and consensual answers to these questions for the participants.

To study the clinical and laboratory relationships of fatty liver disease in a group of obese children and to investigate whether circulating adiponectin is related to fatty liver disease.Two hundred-ninety obese patients (age 4-18 years) were studied. Baseline body mass index-standard deviation score (BMI-SDS), acanthosis nigricans, blood pressure, plasma lipids, uric acid, alanine aminotransferase (ALT) and adiponectin were assessed, and a standard oral glucose tolerance test was performed. Insulin resistance (RI) was estimated by the homeostasis model assessment (HOMA) and liver steatosis was assessed by ultrasound (US). Children were classified as having metabolic syndrome if they met three or more of the following criteria: obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol and impaired glucose metabolism.Fifty-two subjects (18%) had fatty liver by US and 22 (8%) had elevated ALT levels (or =40 U/L). Subjects with steatosis were significantly older (12.2+/-2.4 frente a 11.1+/-2.9 yr), heavier (BMI-SDS: 4.5+/-1.5 frente a 3.8+/-1.3), and more RI (HOMA: 3.7+/-1.5 frente a 2.4+/-1.4), but were comparable in gender, pubertal status and racial distribution to those with normal US. The prevalence of metabolic syndrome and acanthosis nigricans were also higher in the steatosis frente a the normal US group. Serum adiponectin concentration was inversely correlated with age, HOMA, ALT and uric acid and directly correlated with HDL-cholesterol. In a multiple logistic regression analysis, BMI-SDS, HOMA and serum adiponectin, but not age, uric acid or triglycerides, were the covariates independently associated with the presence of steatosis (odds ratio 1.4 [1.1-1.9]; 1.3 [1.1-1.6] and 0.9 [0.8-0.9], respectively).Obesity and RI are risk factors for liver steatosis in children and adolescents. Decreased serum adiponectin is closely and independently associated with steatosis.

Cushing's disease (CD), which is caused fundamentally by a pituitary microadenoma, is a rare endocrine disease in the paediatric age and which is associated with significant morbidity. The current treatment of choice for CD is trans-sphenoidal selective adenomectomy resulting in long-term remission rates. Pharmacological management of CD is directed at decreasing adrenal steroid secretion. Ketoconazole inhibits adrenal enzyme activity and decreases cortisol secretion. Our patient is a girl of 13 years and eight months of age with CD. The clinical manifestations were obesity, decrease in growth rate, Cushingoid phenotype, headache and arterial hypertension. The hormone determinations showed elevated values of UFC and ACTH. The circadian rhythm cortisol and ACTH and the short and long dexamethasone tests of provide definitive diagnosis of CD. The cranial MRI with gadolinium suggests the presence of microadenoma in the right pituitary lobe. The diagnosis is confirmed after performing a selective catheterisation of the inferior petrosal sinuses with CRH stimulus. While waiting for trans-sphenoidal surgery, the treatment with ketoconazole (200mg/24h) controlled the hypercortisolism. After the surgical procedure, the patient received replacement therapy with hydrocortisone for 1 month. At the present time, the patient, without fulfilling the post surgery cure criteria, has been 2 and a half years in clinical and hormonal remission.

Diabetes mellitus (DM) is an increasing complication of cystic fibrosis (CF). It is associated with enhance morbidity. Continuous glucose monitoring system (CGMS) could detect glucose disorders earlier than other screening tests usually used.To compare oral glucose tolerance test (OGTT), HbA(1c) and CGMS in patients with CF and recent disorders of glucose homeostasis and to analyse changes in nutritional status and/or pulmonary function.Thirteen patients with CF (11-22 years, 7 males) were studied using OGTT, HbA(1c) and CGMS. All of them had newly diagnosed glucose disturbances. They were not receiving steroid therapy or had an underlying illness. In all subjects we compared: HbA(1c) levels (%), fasting and 2-hours glucose OGTT (mg/dl) and glucose CGMS values (overall, fasting, 2-hours post mean-meals and excursions140mg/dl at any time). Furthermore, body mass index, forced expiratory volume in the first second (%) and forced vital capacity (%) were evaluated in the previous year and at the time of the study. We also analysed exocrine pancreatic function and CF-mutation.Mean age at diagnosis of glucose disturbance was 16.4 years. All patients had insufficient exocrine pancreatic function and 11/13 presented DeltaF508 CF-mutation. Only one patient was diagnosed with DM using OGGT and 7/13 (53.8%) with CGMS. A total 77% of patients had poor nutritional status and/or pulmonary function at time of diagnosing the glucose disorder. Only 4 patients had abnormal HbA(1c) levels.CGMS allows a better detection of glucose disorders than OGTT. Glucose homeostasis abnormalities are associated with a decrease in nutritional status and/or pulmonary function. HbA(1c) does not aid in the early diagnose of glucose disorders.

There is wide variation in the clinical expression of 45,X/46,XY mosaicism. Ninety percent of prenatally diagnosed boys have normal male phenotype at birth, while those diagnosed postnatally show a wide spectrum of phenotypes, ranging from Turner syndrome, mixed gonadal dysgenesis, and male pseudohermaphroditism to apparent normality. We report the clinical, cytogenetic, endocrinologic and histologic findings in three boys with an apparently normal male phenotype and 45,X/46,XY mosaicism who were diagnosed postnatally because of their short stature. With the exception of one patient with Turner stigmata, no other abnormal features were found. No correlation between the proportion of 45,X/46,XY cell lines in blood, gonads and phenotype was found. Both prenatally and postnatally diagnosed boys with normal male phenotype must be followed-up because they can develop late-onset abnormalities, such as dysgenetic testes leading to infertility or neoplastic transformation, and short stature, which could be improved with growth hormone therapy.

To asses the prevalence of celiac disease and to evaluate the clinical effects of a gluten-free diet on metabolic control and growth in children and adolescents with type 1 diabetes mellitus (DM1).We performed a retrospective study of 261 patients with DM1. Diagnosis of celiac disease was based on the presence of endomysium and tissue transglutaminase antibodies in serum and was confirmed by intestinal biopsy. The impact of a gluten-free diet on metabolic control (mean annual HbAlc values), growth (height and annual growth velocity) and nutritional status (body mass index) was evaluated. Patients diagnosed with DM1 and subsequently with celiac disease were compared with a control group of patients with DM1 only.Twenty-one (8%) of the 261 diabetic patients were diagnosed with celiac disease and 19% also had another associated autoimmune disease. No significant differences were found in growth or metabolic control after withdrawal of gluten from the diet.We found a high prevalence of celiac disease in our type 1 diabetes population. A gluten-free diet had no effects on metabolic control of diabetes or on height or weight. Nevertheless, given the high prevalence of celiac disease and the possible development of long-term complications, such as lymphoma and osteoporosis, we recommend systematic screening in all diabetic patients, especially in the first 5 years after diagnosis of DM1.

To determine the efficacy and safety of continuous subcutaneous insulin infusion therapy in a group of children and adolescents with type 1 diabetes mellitus.Data from 17 patients were collected during the first year of continuous subcutaneous insulin infusion treatment. All patients were followed-up at our diabetic pediatric clinic. HbA1c, body mass index, insulin dose, severe hypoglycemic episodes, and diabetic ketoacidosis events before and after initiation of pump therapy were compared.The mean age was 14.02 +/- 3.70 years and the mean diabetes duration was 5.81 +/- 3.31 years. HbA1c decreased from 8.12 +/- 1.46 to 7.52 +/- 0.87 % after 2 months of therapy and this decrease was maintained throughout the first year of continuous subcutaneous insulin infusion treatment. Insulin dose decreased from 0.99 +/- 0.24 to 0.84 +/- 0.18 U/kg/day after 1 year of treatment. Body mass index remained unchanged. There were fewer severe hypoglycemic events after the start of insulin pump therapy (0.47 +/- 1.23 events/patient in the 6 months before continuous insulin infusion, 0.29 +/- 1.20 episodes in the first 6 months of insulin pump therapy and 0.06 +/- 0.24 in the period from 6 to 12 months of the treatment). There were 3 ketoacidosis episodes, all in the same patient.Continuous subcutaneous insulin infusion is a safe and effective alternative in the treatment of children and adolescents with type 1 diabetes mellitus. It improves metabolic control and decreases the number of severe hypoglycemic episodes.

Graves' disease, which is the main cause of hyperthyroidism in the pediatric age group, is very rare in pre-school children. We describe the cases of four girls, aged less than 6 years old, out of a total of 30 patients diagnosed with Graves' disease between 1985 and 2004. Investigations were motivated by tachycardia, chronic diarrhea, language development delay or thyroid nodules detected by cervical ultrasonography. In three of the four patients height and bone age were advanced. In all patients goiter was small or absent. None of the patients had ophthalmic disease. In all patients free T3 and T4 were elevated and thyroid-stimulating hormone was suppressed. Three patients were positive for thyroid-stimulating immunoglobulins (the method was not available for the oldest case). Two patients showed complete resolution after 5 years of treatment with carbimazole. The remaining two patients are still under treatment and no adverse effects have been documented.

La hipoglucemia (HG) es un problema muy frecuente en el periodo neonatal, que conlleva riesgo de secuelas neurologicas. Su frecuencia podria estar mal estimada debido, por una parte, a la falta de consenso sobre la defi nicion analitica de HG en el recien nacido (RN) y, por otra, a la difi cultad tecnica de la medicion de la glucemia en los rangos mas bajos. El gold standard consiste en determinar la glucosa plasmatica por metodos enzimaticos en el laboratorio, pero esto requiere multiples extracciones. En los neonatos con riesgo incrementado de HG, esta se mide habitualmente de manera intermitente y en sangre capilar. Aunque la correlacion de los niveles de glucosa –determinados mediante glucemia capilar o monitorizacion continua de glucosa intersticial (MCGI)– con los resultados del laboratorio es aceptable, en los rangos inferiores esta correlacion no es tan buena. En la actualidad existen dos tipos de metodos de determinacion continua de glucosa: el metodo «ciego» o retrospectivo y el «abierto» o prospectivo (que permite la vision continuada de la glucosa en tiempo real). Determinados cambios introducidos en el algoritmo de calibracion de algunos de estos sistemas (Paradigm Veo, Medtronic, Northridge, California, Estados Unidos) han mejorado la sensibilidad en rangos hipoglucemicos. Ya en 2005, Beardsall et al., en su estudio de MCGI con un sistema «ciego» CGMS (MiniMed, Medtronic, Northridge, California, Estados Unidos) realizado en 16 RN de 32 semanas de gestacion ingresados en la UCI, mediante la determinacion intermitente de glucemia capilar, comparandola con un sistema «ciego» de MCGI (CGMS System GoldTM, Medtronic, Northridge, California, Estados Unidos). Los RN fueron monitorizados desde las primeras horas de vida hasta que desaparecio el riesgo de HG, o en su defecto hasta los 7 dias (tiempo medio 80 horas), defi niendose las HG por debajo de 47 mg/dL (2,6 mmol/L). Estos autores encontraron una buena correlacion entre glucosa sanguinea e intersticial. Detectaron HG en el 32% mediante determinacion sanguinea y en el 44% con MCGI, y constataron que el 81% de los episodios de HG no se detectaban con mediciones sanguineas. En 107 episodios de HG evidenciados en 34 ninos la duracion fue superior a 30 minutos. Ademas, senalaron que la incidencia de niveles bajos de glucemia fue similar en ninos con diferentes factores de riesgo, pero no mostraron los datos. Este estudio, ademas de mostrar que la MCGI con CGMS System GoldTM fue segura y bien tolerada en un grupo mayor de pacientes y en todo tipo de recien nacidos, demuestra que dicha monitorizacion puede prolongarse con el mismo sensor hasta 7 dias, lo que permite reducir el gasto y las molestias al paciente. El trabajo tambien evidencia que los episodios de HG fueron frecuentes y recurrentes, tambien en RN >32 semanas de gestacion. Un punto debil del estudio es que se incluyo una poblacion muy heterogenea, lo que difi culta la valoracion del riesgo de HG, pues este puede variar segun el peso, la edad gestacional y la existencia de determinadas patologias neonatales. En relacion con trabajos similares previos, Harris et al. encontraron una mejor correlacion entre la glucosa intersticial y la glucosa capilar. Aunque existen algunos estudios en animales y personas adultas que sugieren la precision de los metodos de MCGI en los rangos bajos, esta precision sigue estando cuestionada, lo que podria condicionar una sobrestimacion de la hipoglucemia. Estas dudas razonables deberian ser resueltas con nuevos estudios prospectivos utilizando ya las nuevas tecnologias de MCGI en tiempo real, mas sensibles, que ademas permitirian un diagnostico y tratamiento mas precoz de las hipoglucemias. Es evidente que las alteraciones de la homeostasis de la glucosa son clinicamente relevantes en el periodo neonatal. Sin embargo, quedaria por defi nir de manera precisa su signifi cacion patologica ulterior, para lo cual son esenciales el seguimiento y la valoracion evolutiva del desarrollo neurocognitivo de los ninos con HG neonatal. ■ Fecha de recepcion: 17 de mayo de 2010 Fecha de aceptacion: 20 de mayo de 2010

Resumen: Este artículo expone el documento consenso al que ha llegado el Grupo de Trabajo de Diabetes Pediátrica de la Sociedad Española de Endocrinología Pediátrica de la Asociación Española de Pediatría sobre el tratamiento con infusión subcutánea continua de insulina en diabetes tipo 1 en la edad pediátrica. Se recogen los aspectos prácticos sobre requisitos, indicaciones, contraindicaciones, candidatos, ventajas e inconvenientes de dicho tipo de tratamiento. Las conclusiones se basan en la revisión de los consensos internacionales basados en la evidencia y en el acuerdo de los participantes. Abstract: This article reports on the Spanish Position Statement for the Diabetes Pediátric Group for the Spanish Pediatric Endocrinology Society (SEEP) on continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes. The practical issues about their indications, appropriate candidates, feasibility, and limits are outlined. The conclusions are based on the comprehensive review and balanced assessment of the evidence base on the international consensus and consensual answers to these questions for the participants.