Short stature diagnosis and referral

The "360° GH in Europe" meeting, which examined various aspects of GH diseases, was held in Lisbon, Portugal, in June 2016. The Merck KGaA (Germany) funded meeting comprised three sessions entitled "Short Stature Diagnosis and Referral, " "Optimizing Patient Management, " and "Managing Transition." Each session had three speaker presentations, followed by a discussion period, and is reported as a manuscript, authored by the speakers. The first session examined current processes of diagnosis and referral by endocrine specialists for pediatric patients with short stature. Requirements for referral vary widely, by country and by patient characteristics such as age. A balance must be made to ensure eligible patients get referred while healthcare systems are not over-burdened by excessive referrals. Late referral and diagnosis of non-GH deficiency conditions can result in increased morbidity and mortality. The consequent delays in making a diagnosis may compromise the effectiveness of GH treatment. Algorithms for growth monitoring and evaluation of skeletal disproportions can improve identification of non-GH deficiency conditions. Performance and validation of guidelines for diagnosis of GH deficiency have not been sufficiently tested. Provocative tests for investigation of GH deficiency remain equivocal, with insufficient information on variations due to patient characteristics, and cutoff values for definition differ not only by country but also by the assay used. When referring and diagnosing causes of short stature in pediatric patients, clinicians need to rely on many factors, but the most essential is clinical experience

Impact of adherence on growth response during the first 2 years of growth hormone treatment

Purpose Adherence to growth hormone (GH) treatment impacts clinical outcomes. The aim of this study is to assess the impact of adherence to rhGH treatment (2 years) on auxological outcomes. Methods Multicentric, retrospective observational study in rhGH-naive GHD/SGA children treated with Saizen (R) during >= 2 years. Growth response was assessed by evaluating the change in height standard deviation score (Delta H SDS) and the index of responsiveness (IoR). Adherence was monitored using EasyPod (TM) Connect device. Results A total of 110 patients (3 Spanish centers) were evaluable (GHD n = 76, SGA n = 34). Adherence was 95.6 and 93.9% (year 1, 2). SGA and GHD children showed an increase of 0.6 cm/year and 1.1 cm/year for each 10% adherence modification. Lower adherence was observed in patients with lower pretreatment height velocity (HV) and in patients whose parents had a lower level of education. A positive correlation between index of responsiveness (IoR) during the first and second years with HV SDS during the second year and between IoR2 and adherence (year 1, 2) was observed. The frequency of patients with HV > 1 SD was higher (p = 0.025) among patients with adherence >90%. The best model to predict the height gain(cm) reaching an adjusted R squared of 0.489 involved percentage of adherence, Tanner stage, pretreatment HV, dose of rhGH, and whether the treatment was initiated before or after puberty. Conclusions Adherence during the first 2 years of response was very high >90% and showed a negative association with age, pretreatment HV and treatment duration and a positive correlation with the level of parent education

Evaluating the usefulness and ease of use of a next-generation–connected drug delivery device for growth hormone therapy: qualitative study of health care professionals’ perceptions

Background: Digital solutions targeting children’s health have become an increasingly important element in the provision of integrated health care. For the treatment of growth hormone deficiency (GHD), a unique connected device is available to facilitate the delivery of recombinant human growth hormone (r-hGH) by automating the daily injection process and collecting injection data such that accurate adherence information is available to health care professionals (HCPs), caregivers, and patients. The adoption of such digital solutions requires a good understanding of the perspectives of HCPs as key stakeholders because they leverage data collection and prescribe these solutions to their patients. Objective: This study aimed to evaluate the third generation of the easypod device (EP3) for the delivery of r-hGH treatment from the HCP perspective, with a focus on perceived usefulness and ease of use. Methods: A qualitative study was conducted, based on a participatory workshop conducted in Zaragoza, Spain, with 10 HCPs experienced in the management of pediatric GHD from 7 reference hospitals in Spain. Several activities were designed to promote discussion among participants about predefined topics based on the Technology Acceptance Model and the Unified Theory of Acceptance and Use of Technology to provide their perceptions about the new device. Results: Participants reported 2 key advantages of EP3 over previous easypod generations: the touch screen interface and the real-time data transmission functionality. All participants (10/10, 100%) agreed that the new device should be part of a digital health ecosystem that provides complementary functionalities including data analysis. Conclusions: This study explored the perceived value of the EP3 autoinjector device for the treatment of GHD by HCPs. HCPs rated the new capabilities of the device as having substantial improvements and concluded that it was highly recommendable for clinical practice. EP3 will enhance decision-making and allow for more personalized care of patients receiving r-hGH. JMIR Hum Factors 2023;10:e46893 doi:10.2196/4689

Hipopituitarismo. Una causa poco frecuente de retraso psicomotor

Sr. Editor: El hipopituitarismo es un síndrome clínico, resultante de la secreción insuficiente o ausencia completa de secreción de una o varias hormonas hipofisarias anteriores. Aunque típicamente el diagnóstico se suele realizar en período neonatal, en ocasiones, su primera manifestación puede ser un retraso psicomotor en loa lactantes, por lo que el diagnóstico precoz puede prevenir el deterioro neurocognitivo, evitando la aparición de secuelas neurológicas. Se presentan 2 casos de hipopituitarismo, diagnosticados a raíz de la presencia de retraso psicomotor en periodo de lactante: Caso 1 Recién nacida mujer a término, controlada por aumento craneal del diámetro biparietal y ventriculomegalia de ventrículos laterales con colpocefalia, sin signos de hipertensión intracraneal. Con 20 meses persiste ausencia de bipedestación y lenguaje; estudio analítico neurometabólico, carga viral de citomegalovirus, electroencefalograma, potenciales evocados auditivos, fondo de ojo, cariotipo y cribado neonatal normal. A los 21 meses presenta longitud de 70, 3 cm (–4, 8 DE) y peso de 6, 9 kg (–3, 71 DE), baja velocidad de crecimiento y estudio analítico hormonal compatible con déficit de hormona de crecimiento (GH), con el resto de estudios, incluido el tiroideo, normal. En el estudio genético arrays-CGH se detecta una deleción 1q25.2, asociado a haploinsuficiencia del gen LHX4..

Deficiencia de vitamina D en niños aragoneses sanos

Introducción: la principal acción de la vitamina D es mantener la concentración de calcio y fósforo dentro del rango fisiológico permitiendo el metabolismo normal y la mineralización ósea. Últimamente, se han descrito receptores de vitamina D en muchos tejidos y se ha relacionado la deficiencia de la vitamina D no solo con raquitismo y osteomalacia, sino también con mayor riesgo de diabetes, obesidad, enfermedades cardiovasculares, oncológicas, infecciosas y autoinmunes. Objetivo: el objetivo del estudio fue conocer la concentración de vitamina D en una población pediátrica sana y comprobar sus factores influyentes, así como analizar la situación actual de profilaxis de vitamina D y valorar la eficacia de las recomendaciones actuales. Métodos: se seleccionaron 107 pacientes sanos, de edades comprendidas entre uno y 15 años, que precisaron una analítica sanguínea como preoperatorio de cirugía menor, cuya patología no influyera en los parámetros del estudio. Resultados: la muestra estaba constituida en un 78, 5% por varones y presentaba una media de edad de 7, 17 ± 3, 79 años. La concentración media de vitamina D fue de 26, 07 ± 7, 11 ng/ml y hasta un 72, 9% presentaba niveles insuficientes. Se dividió la muestra en dos grupos: pacientes con hipovitaminosis D y pacientes con niveles óptimos de vitamina D. Se observó en el grupo con hipovitaminosis un predominio de varones, mayor índice de masa corporal y la presencia de fototipos extremos así como provenientes de padres inmigrantes. También presentaban mayor riesgo de hipovitaminosis los que no habían realizado profilaxis durante el primer año de vida. Conclusiones: se pone de manifiesto el alto porcentaje de población infantil sana con déficit de vitamina D y que las recomendaciones actuales de profilaxis no son llevadas a cabo por la población como recomiendan las guías actuales Background: the main action of vitamin D is to maintain the concentration of calcium and phosphorus within the physiological range, allowing normal metabolism and bone mineralization. Vitamin D receptors have recently been described in many tissues, therefore vitamin D deficiency has been related not only to rickets, but also to increased risk of diabetes, obesity, cardiovascular, oncological, infectious and autoimmune diseases. Objective: the aim of the study was to know the vitamin D concentration in a healthy pediatric population and to verify its influential factors, as well as to analyze the current situation of vitamin D prophylaxis and to evaluate the effectiveness of current recommendations. Methods: one hundred and seven healthy patients aged between one and 15 years were selected, who required a blood test as a preoperative minor surgery and whose pathology did not influence the parameters of the study. Results: the sample analyzed had a total of 78.5% males and a mean age of 7.17 ± 3.79 years. Mean values of vitamin D were 26.07 ± 7.11 ng/ml; up to 72.9% had insufficient levels. The sample was divided into two groups: patients with hypovitaminosis D and patients with optimal vitamin D levels. A predominance of males with a higher body mass index, from immigrant parents, and the presence of extreme phototypes were observed in the hypovitaminosis group. There was also a higher risk of hypovitaminosis in those who had not performed prophylaxis during the first year of life. Conclusions: the high percentage of healthy children with vitamin D deficiency is evident, and current recommendations for prophylaxis are not carried out by the population as recommended by current guidelines

Evolución del riesgo cardiometabólico en pacientes supervivientes de leucemia aguda infantil

Introducción: los supervivientes de leucemia aguda (LA) infantil presentan un riesgo incrementado de alteraciones metabólicas y cardiovasculares que aumentan su morbimortalidad a largo plazo.Objetivo: estimar la prevalencia de obesidad, resistencia a la insulina, dislipemia e hipertensión arterial como factores de riesgo cardiometabólico (FRCM) en un grupo de supervivientes de LA infantil, y analizar las posibles causas asociadas a su desarrollo.Material y métodos: estudio observacional retrospectivo en 47 supervivientes de LA tratados en un periodo de 4 años, que recibieron seguimiento durante 10 años.Resultados: el 40% de los participantes presentaron al menos un FRCM durante el seguimiento, siendo la dislipemia (aumento LDL) el más frecuente (38, 3%), seguido de obesidad/sobrepeso (31, 9%) y HTA sistólica (23, 4%). El sexo femenino se estableció como factor de riesgo parael desarrollo de todos ellos (RR 1, 6; RR 3, 16; RR 1, 69; p < 0, 05). Ningún superviviente desarrolló diabetes mellitus, pero sí resistencia a la insulina el 19, 4%. Los pacientes con leucemias de peor pronóstico presentaron mayor riesgo de desarrollar obesidad, resistencia a la insulina y aumento de LDL (RR 3, 56; RR 4, 08; RR 2, 53; p < 0, 05). Los pacientes tratados con trasplante de progenitores hematopoyéticos presentaron mayor riesgo de obesidad, aumento de LDL e HTA sistólica (RR 2, 86; RR 2, 39; RR 3, 12; p<0, 05). La radioterapia se asoció de igual modo con un incremento de resistencia a la insulina e hipertensión arterial sistólica (RR 2, 47; RR 2, 53; p < 0, 05).Conclusiones: existe un aumento en la prevalencia de obesidad/sobrepeso, dislipemia, resistencia a la insulina y alteración de la tensión arterial sistólica en supervivientes de leucemia aguda infantil a lo largo del tiempo, especialmente en aquellos con enfermedades y tratamientos más agresivos. Background: Survivors of childhood acute leukemia (AL) face an increased risk of metabolic and cardiovascular late effects which increase their long-term morbimotality. Objective: To assess the prevalence of obesity, insulinresistance, dyslipidemia and hypertension as cardiometabolic risk factors in survivors of a childhood AL, and also to determine possible causes for these adverse cardiometabolic traits. Material and methods: A retrospective cohort study of 47 pediatric acute leukemia survivors diagnosed between 0-15 years, with a ten years follow-up. Results: Forty percent of participants had at least one cardiometabolic risk factor. Dyslipidemia (increased LDL cholesterol) was the most frequent (38.3%), secondly overweight/obese (31.9%), followed by systolic hypertension (23.4%). Females in contrast to males had an increased risk of developing all three risk factors (RR 1.6; RR 3.16; RR 1.69; p < 0.05). Only 19.4% of participants developed insulin resistance, while none were diagnosed with diabetes mellitus. High risk acute leukemia survivors were significantly more likely than low risk leukemia survivors to manifest multiple cardiometabolic traits like overweight/obesity, insulin resitance and dyslipidemia (RR 3.56; RR 2.39; RR 2.53; p < 0.05). Also, those who received hematopoietic cell trasplantation had an increased prevalence of overweight/obesity, increased LDL-cholesterol and systolic hypertension. Radiotherapy treatment was also associated with insulin resitance and systolic hypertension (RR 2.47; RR 2.53; p < 0.05). Conclusions: There is an increased risk of overweight/obesity, dyslipidemia, insulin resistance and systolic blood pressure modification in childhood acute leukemia survivors, specially in those who were diagnosed as a high risk acute leukemia and those treated with more aggressive treatments

Enhancement of the magnetic anisotropy of nanometer-sized Co clusters: influence of the surface and of the inter-particle interactions

We study the magnetic properties of spherical Co clusters with diameters between 0.8 nm and 5.4 nm (25 to 7500$ atoms) prepared by sequential sputtering of Co and Al2O3. The particle size distribution has been determined from the equilibrium susceptibility and magnetization data and it is compared to previous structural characterizations. The distribution of activation energies was independently obtained from a scaling plot of the ac susceptibility. Combining these two distributions we have accurately determined the effective anisotropy constant Keff. We find that Keff is enhanced with respect to the bulk value and that it is dominated by a strong anisotropy induced at the surface of the clusters. Interactions between the magnetic moments of adjacent layers are shown to increase the effective activation energy barrier for the reversal of the magnetic moments. Finally, this reversal is shown to proceed classically down to the lowest temperature investigated (1.8 K).Comment: 13 figures submitted to Phys. Rev.