Ten years of clinical experience with biosimilar human growth hormone: a review of safety data.

Safety concerns for recombinant human growth hormone (rhGH) treatments include impact on cancer risk, impact on glucose homeostasis, and the formation of antibodies to endogenous/exogenous GH. Omnitrope® (biosimilar rhGH) was approved by the European Medicines Agency in 2006, with approval granted on the basis of comparable quality, safety, and efficacy to the reference medicine (Genotropin®). Additional concerns that may exist in relation to biosimilar rhGH include safety in indications granted on the basis of extrapolation and the impact of changing to biosimilar rhGH from other rhGH treatments. A substantial data set is available to fully understand the safety profile of biosimilar rhGH, which includes data from its clinical development studies and 10 years of post-approval experience. As of June 2016, 106,941,419 patient days (292,790 patient-years) experience has been gathered for biosimilar rhGH. Based on the available data, there have been no unexpected or unique adverse events related to biosimilar rhGH treatment. There is no increased risk of cancer, adverse glucose homeostasis, or immunogenic response with biosimilar rhGH compared with the reference medicine and other rhGH products. The immunogenicity of biosimilar rhGH is also similar to that of the reference and other rhGH products. Physicians should be reassured that rhGH products have a good safety record when used for approved indications and at recommended doses, and that the safety profile of biosimilar rhGH is in keeping with that of other rhGH products.

Diagnóstico diferencial de la hipoglucemia en el niño / Differential diagnosis of hypoglycemia in infants and children

El adecuado conocimiento fisiopatológico de la homeostasis de la glucosa es fundamental para realizar un diagnóstico precoz y evitar las graves consecuencias neurológicas derivadas de la hipoglucemia en el niño. Definimos hipoglucemia como un nivel de glucosa en sangre inferior a 2,5 mmol/l (45 mg/dl) a cualquier edad, con consideraciones particulares para los recién nacidos y prematuros. La clínica que produce la hipoglucemia se relaciona con la activación del sistema nervioso autónomo y con el déficit neurológico, aunque en numerosas ocasiones es asintomática. En esta revisión se consideran brevemente las principales causas de la hipoglucemia en la edad pediátrica. Entre ellas las más frecuentes son: Hipoglucemia cetósica: es la forma más común de hipoglucemia en la infancia. Es un proceso relativamente fisiológico ante un período corto de ayuno. El pronóstico es benigno. Hiperinsulinismo: es la primera causa de hipoglucemia persistente en el lactante y la que causa mayor daño neurológico. El diagnóstico se basa en el hallazgo de valores inadecuados de insulinemia y sus efectos (inhibición de la lipólisis) para las concentraciones bajas de glucemia. Se describen los estudios genéticos precisos para determinar la etiología. Panhipopituitarismo: sigue en frecuencia al hiperinsulinismo. Se presenta de forma precoz y se cataloga muchas veces de transitoria debido a su fácil control con aportes de glucosa. En la aproximación diagnóstica de la hipoglucemia es esencial la extracción de muestras en el momento de la hipoglucemia (punto crítico), además de una cuidadosa anamnesis, la búsqueda de antecedentes familiares y la exploración física. A veces es preciso realizar pruebas funcionales, como tests de ayuno o pruebas de estimulación y sobrecarga para llegar al diagnóstico etiológico. El objetivo terapéutico consiste en recuperar la glucemia con aportes orales o parenterales de glucosa y evitar su repetición, con medidas dietéticas o farmacológicas dependiendo de la etiología

Adequate knowledge of the physiopathology of glucose homeostasis is essential to make an early diagnosis and avoid the severe neurological sequelae caused by hypoglycemia in infants and children. We define hypoglycemia as less than 2.5 mmol/l (45 mg/dl) of glucose in blood at any age, with special considerations in neonates and premature infants. The symptoms of hypoglycemia are related to activation of the autonomic nervous system and neurologic deficit, although many patients are asymptomatic. The present review briefly discusses the main causes of hypoglycemia in the pediatric age group. Among the most frequent causes are the following: Ketotic hypoglycemia: this form of hypoglycemia is the most common form of childhood hypoglycemia, and constitutes a relatively physiologic process that occurs after a relatively short period of fasting. The prognosis is benign. Hyperinsulinism: hyperinsulinism is the most frequent cause of persistent hypoglycemia in infants and causes the greatest neurological damage. Diagnosis is based on the finding of an inappropriate insulin level and its effects (inhibition of lipolysis) for low blood glucose levels. The genetic studies required to determine the etiology are described. Panhypopituitarism: panhypopituitarism is the most frequent cause of hypoglycemia after hyperinsulinism. This disorder presents early and is often transitory as it can be easily controlled by glucose intake. Blood sampling at the time of hypoglycemia (critical sample) is essential to diagnosis, in addition to taking a detailed history ­ including family history ­ and carrying out a physical examination. Functional tests, such as fasting study, stimulation and loading tests, are sometimes also required to achieve an etiologic diagnosis. The aim of treatment is to increase blood glucose levels with oral or parenteral glucose intake and to avoid recurrence with dietetic or drug therapy, depending on the etiology