"Escuchemos el lenguaje del niño": normalidad versus signos de alerta / "Let's listen to children language": normality versus warning signs

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[Endocrinological outcome in children and adolescents survivors of central nervous system tumours after a 5 year follow-up]. / Secuelas endocrinológicas en niños y adolescentes supervivientes de tumores del sistema nervioso central tras 5 años de seguimiento.

INTRODUCTION: Given the successful increase in survival rates with the current treatments for central nervous system tumours (CNST), survivors are at high risk for late adverse effects. PURPOSE: To evaluate the endocrine sequelae in children with CNST according to the type of tumour and treatment received. PATIENTS AND METHODS: A retrospective review of the clinical features, auxology, hormone determinations and imaging findings of 38 patients (36.8% females, 63.2% males) with CNST, with a minimum of 5 years follow-up, was performed. RESULTS: The mean age at diagnosis was 5.34 ± 3.07 years, with 76.3% of the patients having at least one hormone deficiency, of which growth hormone (GH) (73.7% of all patients) was the most prevalent, followed by thyrotropin (TSH) (68.4%), corticotropin (31.6%), antidiuretic hormone (28.9%), and gonadotropin (LH/FSH) (21.1%) deficiency. Precocious puberty was found in 21.1% of patients. After 5 years of follow-up, 28.9% were obese. Craniopharyngioma had more hormone deficiencies, obesity and recurrence rates. The most frequently administered treatment was surgery + chemotherapy + radiotherapy, in 47.4% of the patients. Mean final height (20 patients) was -1.2 1.6 SDS, with a mean difference of -0.53 SDS regarding their target height. CONCLUSIONS: 1) The type of tumour and treatment received influence the endocrinological sequelae. 2) The most frequent hormone deficiencies in all types of CNST, regardless of the treatment received, were GH and TSH. 3) Early diagnosis and prompt intervention of endocrine dysfunction can reduce the morbidity and improve quality of life over the long term.

Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC).

BACKGROUND: BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported. PATIENTS AND METHODS: From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors. RESULTS: Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype. CONCLUSION: Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.

Increased leptin/adiponectin ratio and free leptin index are markers of insulin resistance in obese girls during pubertal development.

BACKGROUND: Modifications in body fat in obese patients during puberty determine changes in adipokines that affect insulin sensitivity. AIMS: We hypothesized that the leptin/adiponectin (L/A) ratio and free leptin index (FLI) are good markers of insulin resistance (IR) and total body fat (TBF) during pubertal development. METHODS: A prospective study of 32 obese girls (OG) and age-matched control girls (CG) was performed. OG were divided into those that maintained a weight loss (WL) of >1 SD of initial body mass index (BMI) (WL group, n = 25) and those without WL (NWL group, n = 7). Oral glucose tolerance tests (OGTT) were performed to evaluate IR. Correlations of adipokines, L/A, and FLI with BMI, waist circumference, percentage of TBF (%TBF) and IR were performed over pubertal development. RESULTS: The L/A ratio and FLI were increased in OG at baseline. Both indexes decreased in the WL group as puberty progressed, with no change in CG or NWL. In the WL group, a correlation between L/A and FLI with OGTT and %TBF, and L/A and homeostasis model assessment (HOMA) was found throughout the study. CONCLUSION: The L/A ratio and FLI are good markers to follow changes in IR and %TBF after WL during puberty. Insulin more accurately reflects the changes in IR than HOMA.

Respuesta al tratamiento con hormona de crecimiento durante 3 años en niños pequeños para la edad gestacional: parámetros clínicos, hormonales y metabólicos / Response to 3 years of growth hormone therapy in small for gestational age children: Clinical, hormonal and metabolic parameters

Objetivo: Analizar la eficacia y la seguridad del tratamiento con hormona de crecimiento (GH) durante 3 años en niños pequeños para la edad gestacional (PEG) sin crecimiento recuperador, diagnosticados y tratados en el Servicio de Endocrinología del Hospital Infantil Universitario Niño Jesús de Madrid entre 2003 y 2011. Sujetos y métodos: Se estudiaron retrospectivamente los datos antropométricos y analíticos de 52 pacientes PEG tratados con GH (dosis media: 0,035mg/kg/día), determinando su influencia sobre el crecimiento, composición corporal, maduración ósea, metabolismo de carbohidratos y lípidos, perfilhormona tiroideo y tensión arterial. Resultados: El tratamiento con GH determinó un incremento significativo de la velocidad de crecimiento, máximo en los primeros 12 meses de su administración y en niños menores de 5 años de edad. Los niveles de IGF-I aumentaron significativamente, junto con una aceleración de la maduración ósea, permaneciendo ambos dentro de los límites de la normalidad. Se evidenció un aumento progresivo de los niveles de glucemia en ayunas, HbA1c, insulina basal e índice HOMA (homeostasis model assessment). Se constató una disminución significativa de c-LDL y un aumento de c-HDL. Asimismo, los cocientes colesterol total/c-HDL y c-LDL/c-HDL descendieron de forma significativa. Conclusión: El tratamiento con GH, además de promover el crecimiento físico en pacientes PEG, genera una cierta resistencia a la acción de la insulina y una mejoría de los cocientes de riesgo aterogénico a lo largo del seguimiento, tras 3 años de terapia. Es necesario un seguimiento a talla adulta (AU)

Aim: To analyze the effectiveness and safety of growth hormone (GH) treatment, administered over a 3 year period to children small for gestational age (SGA) without catch-up growth, followed up in the Department of Endocrinology at the University Hospital Niño Jesús in Madrid between 2003 and 2011. Patients and methods: Anthropometric and analytical data from 52 SGA patients receiving GH therapy (mean dose: 0.035mg/kg/day) were retrospectively examined in order to determine its influence on linear growth, body composition, bone maturation, carbohydrate and lipid metabolism, thyroid hormone profile and blood pressure. Results: GH treatment induced a significant increase in growth velocity, with the highest rise occurring during the first 12 months of its administration and in children under 5 years of age. Insulin-like growth factor-I levels increased significantly, along with a significant acceleration in bone maturation, with both parameters remaining within normal limits. A progressive rise in fasting glucose levels, glycosylated hemoglobin, baseline insulin, and homeostasis model assessment index, were also found. Low density lipoprotein cholesterol (LDL-c) levels decreased and high density lipoprotein cholesterol levels (HDL-c) increased significantly. The atherogenic ratios of total-cholesterol/HDL-c and LDL-c/HDL-c also decreased significantly. Conclusion: GH treatment promotes physical growth in SGA patients, generates certain resistance to the action of insulin, and improves atherogenic risk ratios after 3 years of therapy. Long-term monitoring is required until adult height is reached (AU)

Tumores testiculares y paratesticulares en la infancia y adolescencia / Testicular and paratesticular tumors during childhood and adolescence

Introducción: Los tumores testiculares y paratesticulares constituyen el 1-2% de los tumores sólidos en la infancia. Se presenta una serie retrospectiva de 15 casos en menores de 18 años. Resultados: La edad media de los pacientes fue de 9,7 años, siendo prepuberales 6 (media 2,08 ± 1 año) y puberales 9 (media 15,1 ± 1,3 años). La forma de presentación clínica más frecuente fue una masa testicular indolora. Los niveles de alfa-fetoproteína estaban elevados en 5 pacientes (tumores de saco vitelino y carcinomas embrionarios).El estudio anatomopatológico demostró 11 tumores primarios testiculares y 4 paratesticulares (rabdomiosarcomas), siendo el 60% tumores germinales y el resto de células no germinales. El 60% de ellos fueron tumores malignos (2 tumores de saco vitelino, 2 carcinomas embrionarios, un seminoma y 4 rabdomiosarcomas). Entre los tumores benignos, el más frecuente fue el teratoma quístico maduro. La cirugía fue el tratamiento inicial en todos los casos (orquidectomía radical en 13 tumores y enucleación en 2 teratomas, con linfadenectomía retroperitoneal en 4 casos). En 11 de los pacientes el tumor se encontraba en estadio I y en 4 casos (2 carcinomas embrionarios y 2 rabdomiosarcomas), en estadio IV con metástasis pulmonares. Recibieron tratamiento adyuvante con quimioterapia asociada o no a radioterapia 7 de los pacientes (4 rabdomiosarcomas, 2 carcinomas embrionarios y un seminoma). Conclusiones: Los tumores testiculares y paratesticulares en niños prepuberales son un grupo con unas características epidemiológicas, histológicas, evolutivas y terapéuticas, bien diferenciadas respecto de las encontradas en pacientes pospuberales o adultos(AU)

Introduction: Testicular and paratesticular tumors represent 1-2% of the solid tumors in children. We present a retrospective series of 15 cases in patients less than 18 years of age. Results: The mean age of the patients was 9.7 yrs, 6 of them prepubertal (mean age: 2.08 ± 1 yrs) and 9 pubertal (mean age: 15.1 ± 1.3 yrs). The most common clinical form of presentation was a painless testicular mass. The alpha-fetoprotein levels were high in 5 patients (yolk-sac tumors and embryonal carcinomas).The pathological study showed 11 primary testicular tumors and 4 paratesticular tumors (rhabdomyosarcomas), with 60% being germinal tumors and the rest non-germinal. Around 60% were malignant tumors (2 from the yolk-sac tumors, 2 embryonal carcinomas, one seminoma and 4 rhabdomyosarcomas). Among the benign tumors, the most common was the mature cystic teratoma. Surgery was the initial treatment in all of the cases (radical orchiectomy in 13 tumors and enucleation in 2 teratomas, with retroperitoneal lymphadenectomy in 4 cases). In 11 patients the tumor was in stage I, while 4 cases (2 embryonal carcinomas and 2 rhabdomyosarcomas) were in stage IV with pulmonary metastasis. Chemotherapy whether or not combined with radiotherapy was applied in 7 patients (4 rhabdomyosarcomas, 2 embryonal carcinomas and one seminoma). Conclusions: Testicular and paratesticular tumors in prepubertal children show epidemiological, histological, therapeutical and evolutional characteristics well differentiated from postpubertal or adult subjects(AU)

[Response to 3 years of growth hormone therapy in small for gestational age children: clinical, hormonal and metabolic parameters]. / Respuesta al tratamiento con hormona de crecimiento durante 3 años en niños pequeños para la edad gestacional: parámetros clínicos, hormonales y metabólicos.

AIM: To analyze the effectiveness and safety of growth hormone (GH) treatment, administered over a 3 year period to children small for gestational age (SGA) without catch-up growth, followed up in the Department of Endocrinology at the University Hospital Niño Jesús in Madrid between 2003 and 2011. PATIENTS AND METHODS: Anthropometric and analytical data from 52 SGA patients receiving GH therapy (mean dose: 0.035mg/kg/day) were retrospectively examined in order to determine its influence on linear growth, body composition, bone maturation, carbohydrate and lipid metabolism, thyroid hormone profile and blood pressure. RESULTS: GH treatment induced a significant increase in growth velocity, with the highest rise occurring during the first 12 months of its administration and in children under 5 years of age. Insulin-like growth factor-I levels increased significantly, along with a significant acceleration in bone maturation, with both parameters remaining within normal limits. A progressive rise in fasting glucose levels, glycosylated hemoglobin, baseline insulin, and homeostasis model assessment index, were also found. Low density lipoprotein cholesterol (LDL-c) levels decreased and high density lipoprotein cholesterol levels (HDL-c) increased significantly. The atherogenic ratios of total-cholesterol/HDL-c and LDL-c/HDL-c also decreased significantly. CONCLUSION: GH treatment promotes physical growth in SGA patients, generates certain resistance to the action of insulin, and improves atherogenic risk ratios after 3 years of therapy. Long-term monitoring is required until adult height is reached.

[Testicular and paratesticular tumors during childhood and adolescence]. / Tumores testiculares y paratesticulares en la infancia y adolescencia.

INTRODUCTION: Testicular and paratesticular tumors represent 1-2% of the solid tumors in children. We present a retrospective series of 15 cases in patients less than 18 years of age. RESULTS: The mean age of the patients was 9.7 yrs, 6 of them prepubertal (mean age: 2.08 ± 1 yrs) and 9 pubertal (mean age: 15.1 ± 1.3 yrs). The most common clinical form of presentation was a painless testicular mass. The α-fetoprotein levels were high in 5 patients (yolk-sac tumors and embryonal carcinomas). The pathological study showed 11 primary testicular tumors and 4 paratesticular tumors (rhabdomyosarcomas), with 60% being germinal tumors and the rest non-germinal. Around 60% were malignant tumors (2 from the yolk-sac tumors, 2 embryonal carcinomas, one seminoma and 4 rhabdomyosarcomas). Among the benign tumors, the most common was the mature cystic teratoma. Surgery was the initial treatment in all of the cases (radical orchiectomy in 13 tumors and enucleation in 2 teratomas, with retroperitoneal lymphadenectomy in 4 cases). In 11 patients the tumor was in stage I, while 4 cases (2 embryonal carcinomas and 2 rhabdomyosarcomas) were in stage IV with pulmonary metastasis. Chemotherapy whether or not combined with radiotherapy was applied in 7 patients (4 rhabdomyosarcomas, 2 embryonal carcinomas and one seminoma). CONCLUSIONS: Testicular and paratesticular tumors in prepubertal children show epidemiological, histological, therapeutical and evolutional characteristics well differentiated from postpubertal or adult subjects.

Diferente expresividad de la mutacion Asn264LysfsX35 del gen GNAS en una familia afecta de pseudohipoparatiroidismo / Different expression of the Asn264LysfsX35 mutation of the GNAS gene in a family with pseudohypoparathyroidism

El pseudohipoparatiroidismo (PHP) comprende un grupo heterogéneo de enfermedades endocrinológicas que se caracterizan por la existencia de hipocalcemia, hiperfosfatemia y resistencia tisular a la hormona paratiroidea. Se distinguen diferentes formas de PHP. El PHP-Ia es la forma más frecuente y asocia resistencia hormonal múltiple, signos clínicos de osteodistrofia hereditaria de Albright (OHA) y mutaciones en el gen GNAS codificador de la proteína Gsα. El pseudoPHP (PPHP) asocia igualmente mutaciones en el gen GNAS pero cursa con OHA aislada sin anomalías endocrinas. Se presenta una familia con madre afecta de PPHP y dos hijas con PHP-Ia que comparten la misma mutación inactivadora en heterocigosis en el gen GNAS (Asn264LysfsX35). Se discute la diferente expresividad clínica así como el modelo de herencia dominante con impronta genética en el que el fenotipo de la descendencia está deteminado por el sexo del progenitor afecto (AU)

Pseudohypoparathyroidism (PHP) is a heterogeneous group of endocrine diseases characterised by hypocalcaemia, hyperphosphataemia and resistance to PTH. There are different forms of PHP. PHP-Ia is the most frequent form and shows multi-hormonal resistance, GNAS (Gsα) mutations and signs of Albright́s hereditary osteodystrophy (AHO). PseudoPHP (PPHP) have isolated AHO without hormonal resistance and it is also caused by GNAS mutations. We present a family that share the same inactivating GNAS mutation (Asn264LysfsX35); the mother being affected with PPHP and the two daughters with PHP-Ia. We discuss the different clinical phenotypes and the dominant mode of inheritance with genetic imprinting where the phenotype of the offspring depends on the sex of the parent affected (AU)

[Different expression of the Asn264LysfsX35 mutation of the GNAS gene in a family with pseudohypoparathyroidism.]. / Diferente expresividad de la mutacion Asn264LysfsX35 del gen GNAS en una familia afecta de pseudohipoparatiroidismo.

Pseudohypoparathyroidism (PHP) is a heterogeneous group of endocrine diseases characterised by hypocalcaemia, hyperphosphataemia and resistance to PTH. There are different forms of PHP. PHP-Ia is the most frequent form and shows multi-hormonal resistance, GNAS (Gs(α)) mutations and signs of Albright́s hereditary osteodystrophy (AHO). PseudoPHP (PPHP) have isolated AHO without hormonal resistance and it is also caused by GNAS mutations. We present a family that share the same inactivating GNAS mutation (Asn264LysfsX35); the mother being affected with PPHP and the two daughters with PHP-Ia. We discuss the different clinical phenotypes and the dominant mode of inheritance with genetic imprinting where the phenotype of the offspring depends on the sex of the parent affected.

Diabetes tipo 1 y trastornos del comportamiento alimentario / Type 1 diabetes and eating behaviour disorders

Los TCA son cada vez más frecuentes en adolescentes con diabetes mellitus tipo 1, asociándose con mal control metabólico, ganancia ponderal e incremento de las complicaciones microvasculares de la enfermedad. La manipulación de la insulina es el método de purgación más común con el fin de controlar el peso, siendo utilizado según diferentes autores, hasta en el 40% por los adolescentes con diabetes tipo 1. Los criterios de sospecha en la identificación de estos pacientes son: mal control metabólico, preocupación por el peso y el aspecto y angustia psicosocial asociada. El tratamiento debe ser multidisciplinar, formado por psiquiatra, diabetólogo, psicólogo y nutricionista. En la primera fase del tratamiento debe existir un gran flexibilidad, evitando imponer como objetivo cifras estrictas de glucemia, adecuando la dieta a las preferencias del paciente y evitando actitudes recriminatorias o enjuiciadoras. Hay que tener una comunicación lo más fluida e individualizada posible con los adolescentes con diabetes, con el objetivo de que comenten sus problemas y el nivel de satisfacción que tienen con su peso en cada revisión clínica. Además, hay que informarles del posible aumento transitorio de peso al comienzo del tratamiento y, por tanto, se deberá ajustar éste para evitar que tengan una ganancia rápida de peso al inicio de la enfermedad (AU)

Adolescents with diabetes are at increased risk of developing eating, disorders leading to non-compliance with treatment and deterioration of metabolic control, weight gain and increased microvascular complications. Insulin manipulation and omission is the most common weight loss behavior and may be found in almost 40% of these adolescents. A high index of clinical suspicion for the diagnosis of eating disorders is recommended in the diabetes clinic setting to enable early identification of disordered eating attitudes and behavior before they progress to clinical eating disorders. At high risk are patients in mid-adolescence with poor metabolic control, higher body mass index, increased body weight and shape dissatisfaction. Multisystem therapy, involving a multidisciplinary medical team including psychologist, nutritionist and diabetes clinicians, school personnel, family and peer group, is also essential. Treatment should be flexible at first, avoiding very strict glycemic goals, trying to customize diet to patients´ preferences and staying away form judgmental attitudes. Communication with adolescents should be open and individualized, having them in each clinical visit to comment their problems an their degree of satisfaction with their body weight gain at the start of treatment. Thus. Treatment should be adjusted to prevent as much as possible this adverse effect. This article presents a review of the current scientific literature on eating disturbance in type 1 diabetes and synthesizes the existing findings into recommendations for screening and treatment (AU)