Seguimiento clínico y autocuidados en niños y adolescentes con posibles secuelas endocrinológicas tras el cáncer: pasaporte de salud para supervivientes / Clinical follow-up and self-care in children and adolescents with possible endocrinological sequelae after cancer: passport of healthcare for survivors

El tratamiento del cáncer en los niños y adolescentes hamejorado la supervivencia de manera espectacular en losúltimos 30 años. Ahora nos enfrentamos al reto de cuidara estos pacientes, para mejorar su calidad de vida a largoplazo. Esto incluye diagnosticar precozmente los efectos tardíos de los tratamientos que pueden ocurrir en la mayoríade los pacientes supervivientes del cáncer y en concreto ennuestro caso, de los efectos endocrinológicos, que son muyfrecuentes.Se han descrito los efectos endocrinos de quimioterápicos, de la radioterapia, y debemos controlar la aparición deotros, tras el empleo de agentes nuevos en el tratamiento delcáncer, como inmunoterápicos, lo que obliga a monitorizara estos pacientes de forma estrecha.La radioterapia y los agentes alquilantes, muy gonadotóxicos, son el principal factor de riesgo para el desarrollo deefectos tardíos endocrinos. Los glucocorticoides sistémicosa dosis altas pueden afectar a la mineralización ósea y almetabolismo. Nuevos tratamientos como los inhibidores dela tirosin-kinasa y los inmunomoduladores se han descritoque afectan de manera particular al tiroides y a la hipófisis.El seguimiento de los pacientes debe hacerse basado enel riesgo de aparición de los efectos, y en este artículo describimos nuestra propuesta de la atención endocrinológica.Una detallada información sobre el tratamiento del cáncer ylos posibles riesgos futuros, dada de forma progresiva a lospacientes, y ofrecida según su madurez, no debe obviarse, ypuede y debe ser una herramienta que les ayude a conseguirsu mayor salud posible. Hemos de utilizar guías médicasbasadas en la evidencia, y ofrecer documentación disponible para pacientes, que contribuyan a formar e informar alpaciente sobre sus riesgos. Cada centro habrá de organizarsede la mejor manera posible, siendo imprescindible una buenacolaboración multidisciplinar(AU)

Iron-deficiency among blood donors: Donors' opinion on iron supplementation strategy.

BACKGROUND AND OBJECTIVES: Each donation of a single whole blood unit causes a 200-250mg iron loss. The main clinical manifestation of iron deficiency among blood donors is anemia, and every blood collection establishment must have measures in place to minimize and prevent iron depletion in blood donors, according to the European guidelines. However, iron deficiency without anemia is also associated with clinical manifestations. The management of iron deficiency is an acute issue; still, no consensus on its managements exists. One possibility is iron supplementation; however, the acceptability of such a measure is still unknown, so we asked donors' opinions on this topic. MATERIALS AND METHODS: Over a 2-month period, a questionnaire was voluntarily completed by blood donors at the French Military Blood Institute. Gender, age, number of donations in the last 12 months, and preference between iron supplementation and general practitioner consultation for management of iron deficiency were recorded. RESULTS: One thousand nine hundred and seventy-four questionnaires were returned. Donors between ages 18-50 represented 89% of respondents. Altogether, 49% declared that they would rather visit their general practitioner and 46% would rather receive iron supplementation. There were no significant differences correlated with gender or age. However, a higher number of prior donations was significantly associated with a preference for iron supplementation. Frequent female donors had an even stronger preference for iron supplementation. CONCLUSION: Our results showed that there are no strong objections to iron supplementation, which could be an acceptable option for frequent donors - the main population at risk for iron deficiency.

[Incidence of type 1 diabetes in Navarre, 2009-2012]. / Incidencia de la diabetes tipo 1 en Navarra, 2009-2012.

BACKGROUND: A north-south gradient for the incidence of type 1 diabetes (DM1) has been described in Europe, with higher incidence in the northern countries. The aim of this study is to describe the incidence data for DM1 in Navarre from 2009-2012, regardless of age at diagnosis, including geographical distribution and age and sex characteristics. PATIENTS AND METHODS: Prospective study, based on one primary and three secondary sources. Completeness of records was assessed, using the capture-recapture method, at 98.42%. Incidence was compared between different gender and age groups by estimating the incidence ratio using Poisson regression methods. To compare the incidence between the different geographical areas, adjustments were made to the values obtained by the indirect standardization method. RESULTS: A total of 216 cases were detected (incidence: 8.4/100,000 population/year; 95 % CI: 7.3-9.5). Incidence was higher in children than in adults, although the number of new cases was highest in those aged over 15. The age group with the highest incidence was 10 to 14 years; however, the highest percentage of patients fell in the 15 to 29-year-old group. Incidence was higher in men than in women. The incidence rates in the three southern regions were generally higher than the mean for Navarre. CONCLUSIONS: Navarre has a very high incidence of DM1 in children and adults aged 15 to 29. DM1 is more common in men and shows some geographic variability.

Incidencia de la diabetes tipo 1 en Navarra, 2009-2012 / Incidence of type 1 diabetes in Navarre, 2009-2012

Fundamento: En Europa se ha descrito un gradiente norte-sur en la incidencia de diabetes tipo 1 (DM1), con mayor incidencia en los países del norte. El objetivo del presente trabajo consiste en conocer los datos de incidencia de DM1 en Navarra, sin límite de edad al diagnóstico, durante el período 2009-2012, su distribución geográfica y sus características en cuanto a edad y sexo. Pacientes y métodos: Estudio prospectivo, con una fuente primaria y tres secundarias. La exhaustividad del registro se evaluó mediante el método captura-recaptura y fue del 98,42%. La comparación de la incidencia entre los diferentes grupos de género y edad, se ha realizado estimando la razón de incidencia a partir de métodos de regresión de Poisson. Para comparar las incidencias entre las distintas áreas, se ajustaron los valores obtenidos por el método de estandarización indirecta. Resultados: Se detectaron 216 casos (incidencia: 8,4/100.000 habitantes-año; IC 95%: 7,3-9,5). La incidencia en niños fue mayor que en adultos, aunque el número de debuts fue mayor en mayores de 15 años. El grupo de edad con mayor incidencia fue el de 10 a 14 años; en cambio, el mayor porcentaje de pacientes pertenece al grupo de 15 a 29 años. La incidencia en varones fue mayor que en mujeres. Los valores de incidencia en las 3 regiones del sur tienden a superar la media de la Comunidad. Conclusiones: Navarra presenta una incidencia muy alta de DM1 en niños y adultos de 15 a 29 años. La DM1 predomina en varones y muestra cierta variabilidad geográfica (AU)

Background: A north-south gradient for the incidence of type 1 diabetes (DM1) has been described in Europe, with higher incidence in the northern countries. The aim of this study is to describe the incidence data for DM1 in Navarre from 2009-2012, regardless of age at diagnosis, including geographical distribution and age and sex characteristics. Patients and methods: Prospective study, based on one primary and three secondary sources. Completeness of records was assessed, using the capture-recapture method, at 98.42%. Incidence was compared between different gender and age groups by estimating the incidence ratio using Poisson regression methods. To compare the incidence between the different geographical areas, adjustments were made to the values obtained by the indirect standardization method. Results: A total of 216 cases were detected (incidence: 8.4/100,000 population/year; 95 % CI: 7.3-9.5). Incidence was higher in children than in adults, although the number of new cases was highest in those aged over 15. The age group with the highest incidence was 10 to 14 years; however, the highest percentage of patients fell in the 15 to 29-year-old group. Incidence was higher in men than in women. The incidence rates in the three southern regions were generally higher than the mean for Navarre. Conclusions: Navarre has a very high incidence of DM1 in children and adults aged 15 to 29. DM1 is more common in men and shows some geographic variability (AU)

Uptake of perfluorinated compounds by plants grown in nutrient solution.

The uptake rates of three perfluorinated carboxylates and three perfluorinated sufonates by a grass (B diandrus) grown in nutrient solution at two different perfluorinated compounds (PFCs) concentrations were assessed. Grass can be ingested by grazing animals causing the PFCs to enter the food chain, which is a pathway of human exposure to these compounds. A rapid and miniaturized method was developed to determine PFCs in plants, based on a matrix solid-phase dispersion (MSPD) extraction procedure followed by quantitation by HPLC-MS/MS with an MQL in the range from 1 to 9 ng/g. An increase of PFCs levels in plant was observed along the exposure time. Differences in uptake for studied perfluorinated carboxylates were found, showing a decrease with carbon chain length (from 3027 to 1,167 ng/g at the end of assay), whereas no significant differences in absorption were obtained between perfluorinated sulfonates (about 1,700 ng/g). Initially, higher PFC transfer factors (ratio between concentration in plant and concentration in initial nutrient solution) were obtained for plants growing in the nutrient solution at the highest PFC concentration, but these factors became similar with time to plants exposed to the lowest concentration.

Total antioxidant capacity and oxidative stress after a 10-week dietary intervention program in obese children.

UNLABELLED: Dietary and serum total antioxidant capacity (TAC) are considered appropriate tools for investigating the potential health effects of dietary antioxidants consumed in mixed diets. The aim was to analyze the impact of a dietary intervention on macronutrient intakes and to evaluate the improvement on oxidative status after weight loss (WL) by measuring dietary and serum TAC, and urinary F2-isoprostane levels as markers of oxidative stress. Forty-four overweight/obese children (mean age 11.5 years) were enrolled to undergo a 10-week WL program. They were dichotomized at the median of body mass index-standard deviation score (BMI-SDS) change, as high (HR) and low responders (LR) after intervention. Subjects were prescribed with a fixed full-day meal diet, calculated according to their basal metabolic rate and physical activity levels. A validated food-frequency questionnaire was used to retrospectively calculate TAC and daily nutrient intake. The HR subjects were able to reduce anthropometric indices and to improve lipid and glucose profile. They also significantly diminished fat intake (p = 0.013). Moreover, baseline serum TAC values did significantly predict the reduction in urinary F2 isoprostane (B = -0.236 (-0.393 to -0.078); p = 0.014) in the HR group after the WL program. Notably, changes in dietary TAC after the treatment were associated with a decrease in body weight after the 10-week intervention (B = -2.815 (-5.313 to -0.318), p = 0.029) in the HR group. The -ΔSerumTAC/ΔDietaryTAC and the -ΔF2Isoprostane/ΔDietaryTAC ratios revealed that the relationships between oxidative markers and antioxidants dietary intake were more favorable in the HR than in the LR group. CONCLUSION: Our study showed that a 10-week WL program was able to reduce adiposity indices in obese children. Moreover, after the intervention changes in dietary TAC and WL were significantly associated. Our result suggests that specific food with a high TAC content (such as fruits, vegetables, and legumes) could be recommended to improve WL.

Influence of age at diagnosis on glycaemic control evolution in patients with type 1 diabetes.

AIM: The objective of this study was to describe the relationship between age at onset, with no age limits, and glycaemic control evolution from the time of onset in patients with type 1 diabetes (T1D). METHODS: This observational retrospective follow-up study included 716 patients with T1D onset between 1990 and 2008 treated at the Navarre Hospital Complex. The mean (SD) follow-up lasted 10.1 (5.3) years. Information on their HbA(1c) levels was collected at onset and every year thereafter. Generalized additive mixed models and linear models were used, with patients' annual HbA1c levels as the response variable and the number of years since onset together with age at onset as covariates. RESULTS: The evolution of glycaemic control is not linear and differs across all age groups. Children reach their highest values in adolescence, while patients with onset at ages 10-15 years stabilize their HbA(1c) values after 7 or 8 years. In adults, it is notable that an age of onset ≥ 45 years is associated with the worst control. CONCLUSION: A non-linear increase in HbA(1c) levels can be observed from the time of T1D diagnosis, with significant differences across all age groups.

Talla baja y enfermedades raras / Low height and rare diseases

La baja talla constituye el primer motivo de consultaen endocrinología pediátrica. En un alto porcentajesu etiología es clara y obedece fundamentalmentea variantes de normalidad. Sin embargo, en aproximadamenteun 20% esta baja talla es patológica y obliga aestudios exhaustivos.La asociación de enfermedades raras (ER) con tallabaja es altamente frecuente. En este trabajo repasamoslas etiologías de la baja talla en enfermedades raras,describiendo:– las formas genéticas de la hormona de crecimiento(GH) bien sean aisladas o asociadas amalformaciones de la línea media u otras.– aquellas de gran importancia por su repercusiónclínica como el Síndrome de Turner, Síndromede Noonan y el Síndrome de Willi-Prader.– Las frecuentes displasias óseas, con alteracióngenética en algunos casos para el gen SHOX,situado en el brazo corto del cromosoma Xp.La importancia de estos diagnósticos radica en laposibilidad de hacer un tratamiento precoz y eficaz, enalgunos de ellos, con GH.En conclusión, el diagnóstico de enfermedadesraras con baja talla es un reto actual y habitual en endocrinologíapediátrica por los grandes avances de lagenética molecular y la posibilidad de tratamiento enalgunas de ellas. Implica siempre un abordaje multidisciplinariopor la asociación frecuente de patología quepresenta y a su vez, ofrece la posibilidad de realizar eloportuno consejo genético

Low stature is the main reason of consultation inpaediatric endocrinology. In a high percentage of cases,its etiology is clear and fundamentally answers tovariants of normality. However, in approximately 20% ofcases low stature is pathological and requiresexhaustive studies.The association of rare diseases (RD) with lowheight is very frequent. In this article we review theetiology of low height, describing:– The genetic forms of the growth hormone(GH), whether isolated or associated withmalformations of the average line or others.– Those which are of great importance due totheir clinical repercussion, such as Turner’sSyndrome, Noonan’s Syndrome and Willi-Prader’s Syndrome.– The frequent osseous dysplasias, in somecases with genetic alterations of the SHOXgene, situated in the short arm of the Xpchromosome.The importance of these diagnoses lies in thepossibility of carrying out early and efficient treatment,in some of them, with GH.In conclusion, the diagnosis of rare diseases withlow height is a current and normal challenge inpaediatric endocrinology due to the great advances inmolecular genetics and the possibility of treatment insome of them. It always involves a multidisciplinaryapproach due to the frequent association of pathologyit presents, and, in its turn, it offers the possibility of carrying out timely genetic counselling

A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population.

OBJECTIVE: The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation. METHODS: The study was composed of 451 Spanish children and adolescents (49% boys), aged 5-18 year. According to the International Obesity Task Force (IOTF) criteria, the groups included 160 obese, 132 overweight and 159 normal-weight control subjects. RESULTS: One novel (Thr162Arg) and three known nonsynonymous mutations in the MC4R gene (Ser30Phe, Thr150Ile, Ala244Glu) were detected heterozygously. The MC4R mutations were found in three male (one obese and two overweight) and two female subjects (one obese and one overweight). The novel mutation did not appear to lead to an impaired receptor function. An unequivocal relationship of MC4R mutations with obesity in pedigrees together with an impaired function of the encoded receptor could not be established for any of the mutations. CONCLUSIONS: The presence of heterozygous MC4R mutations in obese and overweight subjects indicates that these mutations may be a susceptibility factor for obesity development, but lifestyle factors, such as exercise or sedentary activities, may modify their effect.

[The vacuum chest wall lifter in the treatment of pectus excavatum]. / Empleo de la campana de succión en el tratamiento del pectus excavatum.

Since 2002, the Eckart Klobe vacuum has been used in our Service as an innovate and non-invasive procedure in patients with pectus excavatum. This vacuum method contributes not only to hold promise as a valuable adjunct in minimally invasive surgery, but also as an effective method to lift and fix the funnel for repairing pectus excavatum in some patients. Our experience is limited to the use of this device in 10 patients, during the Nuss technique. This procedure has been useful for safer passage of the introducer, and as a definitive treatment in a 10 years old girl with pectus excavatum and a Haller index of 5.1 with successful result after one year of treatment. The aim of this study is to report the safety and efficacy of this procedure in appropriate patients. Long-term results will be necessary to confirm this method as an alternative to more invasive techniques.

Empleo de la campana de succión en el tratamiento del pectus excavatum / The vacuum chest wall lifter in the treatment of pectus excavatum

Desde hace 3 años, se ha comenzado a emplear la ventosa de Eckart Klobe como un procedimiento novedoso, no invasivo, en el tratamiento del pectus excavatum. La aportación ha sido, no sólo como ayuda en el momento de la cirugía mínimamente invasiva, sino como tratamiento definitivo para el levantamiento y fijación del embudo en algunos pacientes. Nuestra experiencia se limita al empleo del sistema en 10 pacientes en el momento de la realización de la técnica de Nuss, donde se demostró como una gran ayuda para minimizar el riesgo del paso de la férula, y un tratamiento definitivo en una niña de 10 años afecta de un pectus Excavatum con índice de Haller de 5,1 en donde se ha conseguido la corrección de la deformidad, con un aceptable resultado, después de un año de tratamiento. Pretendemos en este trabajo, dar a conocer la eficacia y benevolencia del sistema en pacientes seleccionados adecuadamente. Harán falta más pacientes y años para confirmar el método como una alternativa a la cirugía, algo que pensamos merece la pena intentar (AU)

Since 2002, the Eckart Klobe vacuum has been used in our Service as an innovate and non-invasive procedure in patients with pectus excavatum. This vacuum method contributes not only to hold promise as a valuable adjunct in minimally invasive surgery, but also as an effective method to lift and fix the funnel for repairing pectus excavatum in some patients. Our experience is limited to the use of this device in 10 patients, during the Nuss technique. This procedure has been useful for safer passage of the introducer, and as a definitive treatment in a 10 years old girl with pectus excavatum and a Haller index of 5.1 with successful result after one year of treatment. The aim of this study is to report the safety and efficacy of this procedure in appropriate patients. Long-term results will be necessary to confirm this method as an alternative to more invasive techniques (AU)

Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents.

AIMS: Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene to obesity risk in a Spanish children and adolescent population. METHODS: We designed a sex- and age-matched case-control study. Participants were 185 obese and 185 control children (aged 5-18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPAR gamma 2 mutation and BstNI for ADR beta 3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls. RESULTS: Carriers of the polymorphism Pro12Ala of the PPAR gamma 2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09-4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17-5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPAR gamma 2 and ADR beta 3) was 5.30 (95% CI=1.08-25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43-146.8). CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene for obesity risk was found in a case-control study including children and adolescents.

Diabetes mellitus / No disponible

No disponible

Hipocrecimiento. Consideraciones generales / Hypogrowth. General considerations

El crecimiento es un indicador fundamental del estado de salud del niño. Muchas patologías que ocurren durante la infancia pueden incidir en el mismo y afectar a la talla final de forma evidente. La evolución y seguimiento periódico de la talla y el peso es un control obligado por los pediatras, debiéndose detectar alteraciones tempranas que puedan corresponder a patologías responsables y posibilitar un correcto diagnóstico y tratamiento precoz. El tiempo del crecimiento en la vida de una persona no es largo, y de ello se deriva la importancia de un seguimiento cuidadoso del mismo. En este trabajo se revisarán los factores que interaccionan en el crecimiento, la metodología a seguir en la consulta de atención primaria para establecer un diagnóstico y el seguimiento ante la talla baja. Se incluye la clasificación del hipocrecimiento que permite diferenciar la talla baja denominada idiopática de la patológica (AU)

Obesidad infantil / Childhood obesity

La obesidad en la infancia y en la adolescencia es cada día un motivo de consulta más frecuente. El aumento en la prevalencia de esta enfermedad, que ha sido considerada como una epidemia por la organización mundial de la salud, es preocupante. La obesidad es una enfermedad compleja, cuya etiología está todavía por esclarecer debido a los múltiples factores implicados: ambientales, genéticos, conductuales y de estilo de vida, neuroendocrinos y metabólicos. La persistencia de la obesidad infantil hasta la edad adulta aumenta significativamente el riesgo de padecer diabetes mellitus, enfermedad cardiovascular, hipertensión, colecistitis y colelitiasis. El tratamiento de la obesidad es complicado y son pocos los pacientes que acuden regularmente a las consultas de seguimiento. Para realizar un tratamiento adecuado se requiere un equipo multidisciplinar compuesto de pediatras, dietistas, enfermeras, psicólogos y psiquiatras. El tratamiento con éxito de la obesidad reside en la disminución de la ingesta calórica en relación con el gasto energético, enseñando a la vez hábitos de alimentación y de estilo de vida apropiados que promuevan a largo plazo el mantenimiento del peso ideal. (AU)

[Hypogrowth. General considerations]. / Hipocrecimiento. Consideraciones generales.

Growth is a basic indicator of the state of health of a child. Many pathologies that occur during childhood can have an incidence and affect final height in an evident way. The evolution and periodic follow up in the examination of the health of height and weight is a compulsory control for paediatricians, who must detect early alterations that might correspond to responsible pathologies and make possible a correct diagnosis and treatment as early as possible. The time of growth in the life of a person is not long, and the importance of a careful follow up derives from this. In this paper we review the factors that interact in growth, the methodology to follow in primary health consultation in order to establish a diagnosis, and the follow up when dealing with a low height. We include the classification of growth retardation that makes it possible to differentiate the low height denominated idiopathic from the pathological.

[Childhood obesity]. / Obesidad infantil.

Obesity during childhood and adolescence is an increasingly frequent cause for medical consultation. The increase in the prevalence of this disease, which has been considered as an epidemic by the World Health Organisation, is worrying. Obesity is a complex disease, whose aetiology still remains to be clarified due to the numerous factors involved: environmental, genetic, life style and behavioural, neuroendocrinological and metabolic. The persistence of childhood obesity until adulthood significantly increases the risk of suffering from diabetes mellitus, cardiovascular disease, hypertension, cholecystitis and cholelithiasis. Treatment of obesity is complicated and few patients regularly attend follow up examinations. A multidisciplinary team is required to carry out a suitable treatment, composed of paediatricians, dieticians, nurses, psychologists and psychiatrists. Successful treatment of obesity resides in reducing the calorie intake in relation to energy expenditure, and at the time providing instruction in appropriate eating habits and life styles that in the long term will promote the maintenance of the ideal weight.