Unidad de Endocrinología y Diabetes Pediátrica / Pediatric endocrinology and diabetes unit

La Unidad de Endocrinología y Diabetes Pediátrica del Hospital Universitario Ramón y Cajal ha tenido siempre como objetivo conseguir los más altos estándares internacionales de calidad en la atención al niño y al adolescente. En particular y para el paciente con diabetes, las nuevas tecnologías, así como la educación diabetológica, son el centro de nuestro trabajo, implicando no solo a padres y pacientes sino a los profesores y a todos aquellos que conviven a su alrededor, buscando así el mejor control metabólico y la mejor calidad de vida (AU)

The objective of the Pediatric and Endocrinology Unit of the University Hospital Ramón y Cajal has always been that of achieving the highest international standards of quality in the care of children and adolescents. Specifically, and for the patient with diabetes, the new technologies and education in diabetes are the center of our work, this not only involving parents and patients but also the professors and all those within their surroundings, seeking in this way the best metabolic control and best quality of life (AU)

Enfermedad de Graves con predominio de T3 en la edad pediátrica / T3-predominant Graves' disease in paediatric patients

No disponible

Factores de riesgo cardiovascular en niños y adolescentes españoles con diabetes mellitus tipo 1: evolución a lo largo de 9 años / Nine-year longitudinal study of cardiovascular risk factors in spanish children and adolescents with type 1 diabetes

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 > 200 mg/dl en el 25,3, el 13,3 y el 16%; lipoproteína de alta densidad del colesterol (HDL-c) < 40 mg/dl en el 1,3, el 1,3 y el 4%; lipoproteína de baja densidad del colesterol (LDL-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 < 0,05). Una HbA1c≥ 7,5% en el segundo y el sexto años se asoció de forma significativa a una disminución en el HDL-c z-score de 0,94, y una HbA1c < 7,5% durante ese mismo periodo se asoció significativamente a un aumento del HDL-c z-score del 0,55(p = 0,015). CONCLUSIONES: El peor control metabólico de la DM1 en los primeros años de evolución se asocia a una disminución del HDL-c z-score. El cociente TG/HDL-c podría ser un marcador precoz de riesgo cardiovascular

OBJECTIVES: 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). PATIENTS AND METHODS: 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. 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% 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 > 200 mg/dl: 25.3%, 13.3% and 16%; high density cholesterol lipoprotein < 40mg/dl: 1.3%, 1.3% and 4%; low density cholesterol lipoprotein > 100mg/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 < .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 HbA1c < 7.5% was significantly associated with a 0.55 increase in HDL-C z-score (P = .015) in the same period. CONCLUSIONS: 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

[Nine-year longitudinal study of cardiovascular risk factors in Spanish children and adolescents with type 1 diabetes]. / Factores de riesgo cardiovascular en niños y adolescentes españoles con diabetes mellitus tipo 1: evolución a lo largo de 9 años.

OBJECTIVES: 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). PATIENTS AND METHODS: 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. 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% 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< 40 mg/dl: 1.3%, 1.3% and 4%; low density cholesterol lipoprotein>100mg/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<.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 HbA1c<7.5% was significantly associated with a 0.55 increase in HDL-C z-score (P=.015) in the same period. CONCLUSIONS: 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.

Eficacia del tratamiento con 131I en la enfermedad de Graves pediátrica / Efficacy of treatment with I 131 in paediatric Graves disease

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.ResultadosDesde 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

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 (<18 years of age) with GD, diagnosed from 1982 to 2012. A curative option was offered to patients who did not respond to anti-thyroid drug (AT) at puberty. We analysed, the patient characteristics, TSH, T4, T3 and thyroid antibodies levels, AT response, remission post I131, side effects, and hypothyroidism rates. RESULTS: A total of 50 patients were diagnosed with GD from 1982 to 2012. All patients received AT as initial treatment (mean duration: 35.3±25.9 months). Permanent remission was achieved in 46%. Thyroidectomy was performed in 5 patients, and 14 patients received I131 (mean dose: 10.9±1.09 mCi). Remission with I131 was obtained in 100%. The rate of permanent hypothyroidism was 90%. There was no progression of ophthalmopathy or side effects in any patientst reated with I131.CONCLUSION: Radioiodine treatment of paediatric GD patients is safe, leads to complete remission at the expense of hypothyroidism, and does not exacerbate ophthalmopathy. It can be considered in patients older than 5 years, who do no not respond to AT or with significant side effects with this medication

[Efficacy of treatment with I(131) in paediatric Graves disease]. / Eficacia del tratamiento con (131)I en la enfermedad de Graves pediátrica.

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 (<18 years of age) with GD, diagnosed from 1982 to 2012. A curative option was offered to patients who did not respond to anti-thyroid drug (AT) at puberty. We analysed, the patient characteristics, TSH, T4, T3 and thyroid antibodies levels, AT response, remission post I(131), side effects, and hypothyroidism rates. RESULTS: A total of 50 patients were diagnosed with GD from 1982 to 2012. All patients received AT as initial treatment (mean duration: 35.3±25.9 months). Permanent remission was achieved in 46%. Thyroidectomy was performed in 5 patients, and 14 patients received I(131) (mean dose: 10.9±1.09 mCi). Remission with I(131) was obtained in 100%. The rate of permanent hypothyroidism was 90%. There was no progression of ophthalmopathy or side effects in any patients treated with I(131.) CONCLUSION: Radioiodine treatment of paediatric GD patients is safe, leads to complete remission at the expense of hypothyroidism, and does not exacerbate ophthalmopathy. It can be considered in patients older than 5 years, who do no not respond to AT or with significant side effects with this medication.

Influencia étnica en la prevalencia de síndrome metabólico en población pediátrica obesa / Ethnic influence on the prevalence of metabolic syndrome in an obese pediatric population

Introducción: La obesidad en la edad pediátrica es cada vez más prevalente. La población hispana inmigrante tiene un alto riesgo de obesidad y de diabetes tipo 2. Objetivo: Analizar la influencia étnica en la prevalencia del síndrome metabólico (SM) y sus componentes en una población pediátrica obesa. Pacientes y métodos: Estudio retrospectivo de 616 niños y adolescentes obesos ([IMC>2 DE (Hernández 1998-2004)]: 142 hispanos y 474 caucásicos. Se comparan la prevalencia de SM y sus componentes (criterios modificados Cook 2003): obesidad y ≥2 de los siguientes: colesterol HDL<40mg/dl, triglicéridos >110mg/dl, presión arterial sistólica y/o diastólica >p90 (Task Force 2004) y alteración del metabolismo hidrocarbonado (ADA 2011). Se evalúa también: historia familiar de SM, HbA1c, insulinorresistencia (HOMA), función hepática y evolución del IMC al año de tratamiento con cambios en el estilo de vida. Resultados: El 30,5% de los hispanos presentan SM frente al 15,5% de los caucásicos (OR=2,4 [IC del 95%, 1,5-3,8]), p<0,005]) y OR de 2,5 al ajustar por sexo, IMC-DE y pubertad. Los hispanos presentan mayor insulinorresistencia (58,6% vs 42,86%, p<0,005) y peor evolución del IMC al año de seguimiento. No hubo diferencias en el resto de datos analizados. Encontramos una peor adherencia a las medidas de cambio de alimentación y ejercicio físico en el grupo hispano. Conclusiones: La prevalencia de SM es superior en la población pediátrica hispana obesa que en la caucásica. La peor adherencia al tratamiento de los niños y adolescentes obesos hispanos hace que este grupo de pacientes tenga un riesgo potencialmente mayor de enfermedades cardiovasculares en la vida adulta (AU)

Introduction: Obesity in children is becoming more prevalent. Obesity and type 2 diabetes is higher in the Latin American immigrant population. Objective: To analyze the influence of ethnicity on the prevalence of metabolic syndrome (MS) and its components in an obese pediatric population. Patients and methods: 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-cholesterol <40mg/dl, triglycerides >110mg/dl, systolic and/or diastolic blood pressure >p90 (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. Results: 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<0.005] 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. Conclusion: 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(AU)

[Ethnic influence on the prevalence of metabolic syndrome in an obese pediatric population]. / Influencia étnica en la prevalencia de síndrome metabólico en población pediátrica obesa.

INTRODUCTION: Obesity in children is becoming more prevalent. Obesity and type 2 diabetes is higher in the Latin American immigrant population. OBJECTIVE: To analyze the influence of ethnicity on the prevalence of metabolic syndrome (MS) and its components in an obese pediatric population. PATIENTS AND METHODS: 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-cholesterol <40mg/dl, triglycerides >110mg/dl, systolic and/or diastolic blood pressure >p90 (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. RESULTS: 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. CONCLUSION: 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.

Diabetes tipo 1 y autoinmunidad / Diabetes type 1 and autoimmunity

La diabetes mellitus de tipo 1 es una enfermedad crónica autoinmune caracterizada por la destrucción selectiva de las células beta de los islotes de Langerhans. Este proceso, probablmente causado por uno o más factores ambientales, tiene lugar en individuos genéticamente susceptible portadores de un HLA determinado, y puede ocurrir durante meses o años antes de que la enfermedad se ponga de manifiesto. La autoinmunidad está en relación con células T autorreactivas, es decir, células que desencadenan una reacción autoinmune contra antígenos propios. La fase preclínica de la diabetes puede ser detectada por la presencia de anticuerpos anticélulas beta (ICA), anticuerpos antiinsulina (IAA), y anticuerpos frente a la decarboxilasa del ácido glutámico (GAD). Dadas sus características específicas inmunológicas, genéticas y metabóicas, el riesgo para desarrollar una diabetes de tipo 1ª es bastante predecible. Aunque hoy día aún no disponemos de una estrategia terapétuica adecuada, es importante identificar a estas personas puesto que podrían beneficiarse de actuaciones terapéuticas para prevenir la enfermedad. La diabetes mellitus tipo 1 se asocia con frecuencia a otras enfermedades de etiología o patogenia autoinmune: enfermedad tiroidea autoinmune, en enfermedad celíaca y, en menor grado, a la enfermedad gástrica autoinmune y a la enfermedad de Addison. La determinación de los autoanticuerpos órgano-específicos proporcionan una manera sencilla de cribado de la autoinmunidad en una población susceptible, como es la de los enfermos diabéticos tipo 1, con la posibilidad de prevenir morbilidad y mortalidad (AU)

Type 1 diabetes mellitus (DM1) is a chronic immune mediated disease characterized by the selective destruction of insulin-producing beta cells in the islets of Langerhans. This process, probably caused by one or more environmental factors, takes place in HLA-genetically susceptible individuals and may be present for months or years before the disease manifests itself. Diabetes autoimmunity is related to autoreactive T cells, this is, T cells that trigger an immune reaction against self antigens. The preclinical period of the DM1 can be detected by the presence of islet cell antibodies (ICA), insulin autoantibodies (IAA), and antibodies to glutamic acid decarboxylase (GAD). Because of its specific immunological, genetic and metabolic character, the risk of developing DM1 is very predictable. Even if we still do not have an adequate therapeutic response/strategy it is important to identify those susceptible subjects in order to help them prevent the disease. DM1 is commonly related to other autoimmune diseases: thyroiditis and celiac disease and much less to pernicious anemia and Addison´s disease. The detection of organ specific autoantibodies in an easy way to determine autoimmunity among a susceptible population such as DM1 patients, and thus helping to prevent morbidity and mortality (AU)

Esteatosis hepática, resistencia a la insulina y adiponectina en una población con obesidad / Fatty liver disease, insulin resistance and adiponectin in an obese pediatric population

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 (AU)

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 (AU)

[Fatty liver disease, insulin resistance and adiponectin in an obese pediatric population]. / Esteatosis hepática, resistencia a la insulina y adiponectina en una población con obesidad.

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 (> 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). CONCLUSIONS: Obesity and RI are risk factors for liver steatosis in children and adolescents. Decreased serum adiponectin is closely and independently associated with steatosis.

[Low stature in males with normal phenotype and 45,X/46,XY mosaicism]. / Talla baja en varones con fenotipo normal y mosaicismo 45,X/46,XY.

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.

Talla baja en varones con fenotipo normal y mosaicismo 45, X/46, XY / Low stature in males with normal phenotype and 45, X/46, XY mosaicism

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 (AU)

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 (AU)

[Impact of diagnosis of celiac disease on metabolic control of type 1 diabetes]. / Impacto del diagnóstico de la enfermedad celíaca en el control metabólico de la diabetes tipo 1.

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.

Impacto del diagnóstico de la enfermedad celíaca en el control metabólico de la diabetes tipo 1 / Impact of diagnosis of celiac disease on metabolic contro l of type 1diabetes

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

[Continuous subcutaneous insulin infusion in pediatric patients with type 1 diabetes mellitus]. / Tratamiento con infusión subcutánea continua de insulina en pacientes pediátricos con diabetes mellitus tipo 1.

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.

Disfunción tiroidea autoinmunitaria de presentación variable en una paciente tratada con interferón-alfa / Variable presentation of autoimmune thyroid disorder in a patient treated with interferon-alpha?

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

Interferon-α is the main therapeutic agent in patients with chronic active hepatitis C. Autoimmune thyroid disorders are a frequent and well-known adverse effect of interferon-α. We report the case of a patient with posttransfusion chronic hepatitis C treated with interferon-α on 2 occasions with an interval of 7 years. After the first cycle of interferon-α therapy she presented thyrotoxicosis due to Graves' disease with 2 relapses. After the second treatment, the patient showed hypothyroidism with positive thyroid antibodies

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

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 adolescentes 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 permanece 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