A síndrome dos ovários policísticos (SOP) é uma desordem que afeta pacientes por toda a vida e é caracterizada por hiperandrogenismo e disfunção ovariana, com um amplo leque de sintomas e sinais clínicos. Três diferentes conjuntos de critérios diagnósticos foram estabelecidos para definir essa doença em mulheres adultas, mas existem controvérsias relacionadas ao uso desses critérios na adolescência. Durante a puberdade, o critério de disfunção ovariana usado em adultos não parece aplicável, porque um padrão menstrual irregular e uma menor taxa de ovulação são eventos fisiológicos nesse período da vida. Além disso, uma maior prevalência de morfologia ovariana policística (MOP) pode ser observada nesse período, de forma que a MOP não é um critério útil para se definir a SOP em mulheres jovens. Esses achados sugerem que o hiperandrogenismo é um fator-chave para o diagnóstico da SOP na adolescência. Além disso, como a MOP não está claramente associada com o hiperandrogenismo durante esse período da vida, o termo "síndrome dos ovários policísticos" durante a adolescência cria confusão e pode ser errôneo.

Polycystic ovarian syndrome (PCOS) is a lifelong disorder characterized by hyperandrogenism and ovulatory dysfunction, with a wide spectrum of clinical symptoms and signs. Three different sets of diagnostic criteria have been established in order to define this disease in adult women, but there is controversy regarding the use of these criteria in adolescence. During puberty, the adult criteria for ovulatory dysfunction does not seem applicable, because an irregular menstrual pattern and a decreased ovulatory rate is a physiologic event during this period of life. Also, a higher prevalence of polycystic ovarian morphology (PCOM) may be observed during this period, so PCOM is not a useful criterion to define PCOS in young women. These findings suggest that a key factor to diagnose to PCOS during adolescence is hyperandrogenism. In addition, since PCOM is not clearly associated with hyperandrogenism during this period of life, the term "polycystic ovarian syndrome" during adolescence creates confusion and may be misleading.

Background: Congenital hypopituitarism is an uncommon cause of hypophyseal insufficiency It is less common than growth hormone deficiency which has an incidence of 1:4.000 to 1:8.000 Uve newborns. Early diagnosis ofthis condition is important to prevent impairment of cognitive function, poor growth and alterations in metabolic profile in these patients. Aim: To report 23 patients diagnosed with congenital hypopituitarism. Material and methods: Retrospective review of clinical records of 23 patients (12 males) with congenital hypopituitarism, diagnosed during a 21 years period. In a group of 16 patients a molecular study was performed searching for mutations in HESX1, PROP-1 or POUF-1. Results: Short stature was the most frequent sign at the first evaluation, followed by neonatal hypoglycemia and presence of nistagmus, strabismus, atrophic optic nerve or malformations in the middle Une showed in CNS imaging, suggesting septo-optic-dysplasia. All male patients diagnosed during neonatal period, exhibited micropenis. CNS images showed isolated hypophyseal hypoplasia or associated to an ectopic neurohypophysis in most patients. No patient in the subgroup subjected to molecular analysis had any of the mutations in the searched genes. Conclusions: The diagnosis of hypopituitarism must be based on clinical grounds, speciaUy when hypoglycemia, prolonged jaundice, micropenis or midline alterations are found in the neonatal period.

Insulinoma is a very uncommon tumor in children, with an incidence in adults of 2 per million inhabitants. Clinical manifestations include neuroglycopenic or autonomic manifestations due to hypoglycemia. We describe 2 pediatric patients with insulinoma, characterized by repeated episodes of hypoglycemia associated to high insulin serum levels and presence of a small mass in the pancreas by imaging studies. The diagnosis was very prompt in one case and delayed in the other, emphasizing the need for an appropriate diagnosis of hypoglycemia during childhood

El insulinoma es un tumor muy infrecuente en la edad pediátrica y la incidencia reportada en adultos es de 2 casos por millón de habitantes. La presentación de la enfermedad consiste en la presencia de síntomas neuroglicopénicos y autonómicos desencadenados por los episodios de hipoglicemia. Se describen dos pacientes con insulinoma esporádico. El cuadro clínico consistió en episodios repetidos de hipoglicemia asociados a niveles aumentados de insulina sérica y a imágenes sugerentes de un tumor pancreático. El diagnóstico fue muy oportuno en uno de los casos y muy tardío en el otro, lo que resalta la necesidad de estar muy alerta ante casos de hipoglicemia durante la niñez

Background: A decline in the age of menarche was observed from early 1900s to the 1970s. However, it is not known if a further decline ocurred thereafter. Aim: To evaluate the age of menarche in girls from Santiago, Chile and its relationship with body mass index (BMI) and socioeconomic status. Material and Methods: We studied 1302 healthy girls aged 7 to 19 years. Age of menarche was evaluated through a questionnaire to the patient and her parents. Kaplan-Meier curves were used to determine age of menarche and Cox regression analysis was employed to evaluate the effect of the type of school and BMI on the age of menarche. Results: The mean age at menarche was 12.7±0.04 years. Girls from public and private schools had their period at 12.5±0.1 and 13.05±0.05 years respectively. A negative correlation between z scores for BMIand age of menarche was observed (r-0.3: p =0.001). Girls whose menarche occurred before 11.5 years had higher z scores for BMI and a larger proportion were overweight, compared to girls who had menarche later. Cox regression analysis showed that after adjusment for BMI, age of menarche was similar in both types of schools. Conclusions: Age of menarche is ocurring three months earlier in girls from public schools, which is associated with higher z scores for BMI. Type of school, a marker of socio-economic status in Chile, affects timing of menarche due to differences in body mass index

Background: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). Aim: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). Patients and methods: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine®). Results: At the time of the study, the Z scores for height among children with and without CUG were -1.55 ± 0.22 and -3.24 ± 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 ± 0.5 and 5.6 ± 0.6 ng/ml, respectively). After Somatokine® administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine® administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine®. Conclusions: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG

Introduction: During the last decade the importance of glycaemic control in the prevention of microvascular complications of type 1 diabetes mellitus (DM1) has been demostrated. To achieve this goal, different modalities of intensive therapy have been recommended. Objective: To communicate a novel therapeutic modality employed in paedriatric patients and the metabolic control achieved. Methods: All DM patients < 19 years were included. Insulin treatment was consigned and classified as intensive (at least 3 daily doses, 2 or 3 NPH daily doses, or glargin) or conventional (2 or less doses). Number of doses, mean HbA1c during 2003, results of educative programmes were evaluated and compared. Results: 69 patients (36 females) were studied, 59,7% were pubertal, with a mean age of 12,0 ± 3,7 years. All patients used a basal insulin (69,2% daily dose) and a prandial insulin. Intensive therapy was used by 87% of children. Patients with multiple daily doses received 3 or 4 inyections of a short or rapid acting insulin. Basal insulin was glargine in 10%, twice daily NPH in 28% and thrice daily in 49%. Patients modified dose according to glucose level occured in 88,4%, and 46,4% considered carbohydrate intake. 27% knew the carbohydrate/insulin ratio and 79,7% used additional insulin when eating extra carbohydrates. The BbA1c was 8,6 ± 1,4% without differences in terms of insulin modality used. 30,4% achieved the proposed goals of HbA1c. The total and basal insulin usage correlated with the HbA1c. Conclusions: Multiple modalities of insulin therapy are available, no difference in metabolic control between the modalities was detected. We have achieved very good control in 30% of the patients, only insulin daily dose and basal dose correlated significatively with HbA1c

En la última década se ha demostrado la importancia del control glicémico en la prevención de las complicaciones microvasculares de la DM1. Para lograr este objetivo se ha propiciado el uso de esquemas terapéuticos de insulina intensificados. Objetivo: Comunicar los nuevos esquemas terapéuticos que se utilizan en niños y adolescentes con DM1 y sus resultados en el control metabólico. Método: Se evaluaron los esquemas insulínicos utilizados por todos los pacientes < 19 años en control durante 2003, clasificándolos en tratamiento intensificado (doble o triple dosis de NPH o Glargina) o convencional (< 2 dosis/día). Se consignaron las dosis utilizadas, la HbA1c promedio, el resultado del programa educativo (conocimiento de cantidad de hidratos de carbono, intercambio de alimentos, cambio de dosis según ingesta de hidratos de carbono (HdC) y proporción Insulina/ HdC) y se compararon los resultados obtenidos con las distintas modalidades de tratamiento. Resultados: Se estudiaron 69 pacientes con DM1 (36 mujeres), de 12,0 ± 3,7 años (2-19 años), 59,7% púberes. Todos utilizaban una insulina basal (69,2% de la dosis diaria) y otra prandial; 87% de los pacientes requirieron tres o más dosis diarias de insulina y 13% utilizaba esquema convencional de dos dosis de NPH. Los pacientes en tratamiento intensificado recibían tres o cuatro dosis diarias de insulina prandial, con los siguientes esquemas de insulina basal: dos dosis diarias de NPH (28%), glargina (10%) y tres dosis diarias de NPH (49%). 88,4% de los pacientes modificaba la dosis de insulina rápida según la glicemia y 46,4% consideraba la ingesta de HC; 27% conocía la relación HdC/insulina y 79,7% se colocaba refuerzos adicionales de insulina al comer fuera de sus horarios. La HbA1C del grupo fue de 8,6 ± 1,4%; 30,4% de los pacientes logró el objetivo de HbA1c establecido en el programa, sin diferencias respecto al esquema de insulinoterapia basal utilizado. Por análisis de covarianza sólo la dosis total y basal de insulina se correlacionaron significativamente con la HbA1C (p < 0,05). Conclusiones: Utilizamos una amplia variedad de esquemas terapéuticos con insulina y no encontramos diferencias en control metabólico entre los distintos esquemas. 30% de nuestros pacientes logran adecuado control metabólico. Sólo la dosis total y basal de insulina se correlacionan con los valores de HbA1c

Background: Recent studies in the United States have demonstrated that a significant proportion of girls show thelarche before the age of eight years. Nutritional status, geographic influences and racial factors are known to affect the timing of puberty. Aim: To evaluate the age of onset of puberty, development of secondary sexual characteristics and menarche in Chilean girls, and its relation to obesity and socioeconomic status. Material and methods: Healthy girls attending elementary school, from first to ninth grade in Santiago, Chile, were studied. A pediatric endocrinologist evaluated pubertal development using Tanner classification. Breast development was assessed by inspection and breast palpation. Average age of onset of pubertal events was determined by probit analysis. Results: A total of 758 girls, aged 5.8 to 16.1 years, were recruited. Obesity, defined as a BMI greater than 90th percentile, was found in 24.4%. The age of menarche was 12.7 years, the onset of Tanner stage 2 breast development and pubic hair was at 8.9 and 10.4 years, respectively. Sixteen percent of girls aged 7 to 7,9 years, had thelarche. Upper class girls showed a later onset of breast Tanner stage 4 stage than low-middle class girls. Obesity was not found in logistic regression analysis to be a significant predictive factor in the onset of puberty. Conclusions: The age of menarche has not changed in the last thirty years, but an earlier onset of thelarche has occurred. The high frequency of thelarche between 7 and 8 years suggests that the normal age of breast development should be revised (Rev Méd Chile 2004; 132: 801-8)

Neonatal hyperinsulinism is the most common form of persistent hypoglycaemia during the first year of life. There is an inappropriate oversecretion of insulin in the presence of hypoglycaemia due to a dysfunction of the sulphonylurea receptor in the pancreatic beta-cell. We describe a case of a premature neonate, small for dates, who presented early hypoglycaemia which was difficult to manage, requiring glucose infusional rates of up to 26 mg/kg/min. When the diagnosis was confirmed, medical treatment with octreotide was started. After 72 hours of treatment it was possible to decrease the glucose infusion, which was discontinued at 6 weeks. The follow up of the patient did not reveal any adverse effects, his nutritional condition is adequate and his psychomotor development is normal. The use of octreotide should be considered as an alternative treatment for a child with persistent hyperinsulinism, avoiding the need for surgery which has a high morbidity in this age group

El hiperinsulinismo neonatal constituye la causa más común de hipoglicemia persistente en el menor de 1 año. Existe una secreción inapropiada de insulina en condiciones de hipoglicemia debido a una alteración en el receptor de sulfonilurea en la célula beta pancreática. Se describe el caso de un recién nacido prematuro, pequeño para la edad gestacional, que presentó precozmente hipoglicemias de difícil manejo, requiriendo cargas de glucosa de hasta 26 mg/kg/min. Tras confirmar el diagnóstico se inició tratamiento médico con octreotide. Luego de 72 horas de iniciado el tratamiento se logró disminuir el aporte de glucosa endovenosa, suspendiéndolo a las 6 semanas. En el seguimiento no se han presentado complicaciones derivadas del tratamiento, su situación nutricional es adecuada y su desarrollo psicomotor es normal. El uso de octreotide debe ser considerado como alternativa terapéutica en niños con hiperinsulinismo persistente, evitando la cirugía que presenta alta morbimortalidad, especialmente en este grupo etario

Background: Short stature is the main feature of patients with Turner's syndrome. There is limited information regarding the spontaneous growth of these patients in Chile. Aim: To develop a specific growth chart for Chilean patients with Turner's syndrome. Material and methods: We retrospectively analyzed 668 height measurements from 85 Chilean girls, born after 1968, with 45XO karyotype (minimum 15%), and without an Y chromosome fragment. Patients with hormonal therapy, such as growth hormone or estrogen, except thyroid hormone replacement, were excluded. Results: The karyotypes were 60% 45XO, 25% 45XO, 46XX, and 15% other complex mosaics. The birth length was 46.8 ± 2.1 cm. The final height of our patients was 138,20 ± 7,0 cm. Conclusions: The final height achieved by our patients, is similar to Argentinian and Japanese patients, but is below the mean stature reported for Scandinavian and Northamerican patients who achieve a mean adult height of approximately 147 and 142 cm respectively. The birth length is also lower than that reported in those studies (Rev Méd Chile 2002; 130: 977-84).

Introduction: recent evidence suggests that the onset of puberty among girls is occurring earlier than previously considered in the northern hemisphere. However, this observation might not be applicable to populations of different ethnic origins, such as Chilean children. Objective: to determine the age of onset of puberty in boys and girls attending 3 primary schools in downtown Santiago. The criteria for the determination of puberal development was the prescence of palpable mammary tissue in girls, and a testicular volume of at least 4 ml in boys. Only children with a MBI between the 10th and 95th percentile were analyzed. Subjects and methods: of 332 children recruited, 80 (24%) were excluded because their BMI was above the 95th percentile. Of the remaining 252, 131 were girls. Among girls aged 7 to 7.49 yrs 10% (2/20) had palpable breast tissue, aged 7.5-7.99 25% (4/16), aged 8-8.99 25% (9/36). Among boys the first signs of testicular growth were observed between 9 and 9.49 years as previously described. Conclusion: the onset of puberty among this group of Chilean girls occurs earlier than in the classical literature, but there was no difference in boys. These results suggest that the development of breast tissue in girls between the ages of 7 and 8 years should not be considered necessarily pathological and that the definition of precocious puberty should be re-evaluated

Introducción: existe evidencia en la literatura norteamericana que la edad de inicio de la pubertad en las niñas se estaría adelantando. No existen trabajos que permitan establecer este hecho en nuestra población. Objetivo: evaluar la edad de inicio de desarrollo puberal en niños y niñas que asisten a tres colegios del sector céntrico de Santiago. Sujetos y método: se reclutaron 332 niños, se determinó peso, talla e IMC (Peso/Talla2) y se descartaron los 80 (24%) con IMC < p10 o > p95, ingresando 252 escolares (131 niñas). Se realizó examen físico y se consideró como inicio de desarrollo puberal la aparición de tejido mamario en las niñas y un volumen testicular de 4 cc o mayor en los varones. Resultados: en el intervalo de edad de 7 a 7,49 años habían 2/20 (10%) niñas con botón mamario, en el de 7,5 a 7,99 4/16 (25%) y en el de 8 a 8,99 años 9/36 (25%). En el varón, el primer signo de activación del eje pituitario gonadal apareció en el grupo de 9 a 9,49 años, similar a lo descrito previamente. Conclusión: la edad de inicio del desarrollo puberal en este grupo de niñas chilenas, se estaría adelantando en relación a la literatura clásica1, mientras que en el varón no se demuestran cambios. Estos resultados sugieren que el inicio del desarrollo mamario en niñas entre los 7 y 8 años, no debería considerarse siempre como patológico y que habría que reevaluar la definición de pubertad precoz

Background: McCune-Albright Syndrome (MAS) is characterized by precocious puberty, "cafe au lait" skin lesions and polyostotic fibrous dysplasia. It is caused by 4 post-zygotic mutations of Gas protein with a mosaic distribution. Aim: To describe the clinical presentation and to investigate the presence of the Arg by his substitution (R201H) in 14 girls with MAS. Patients and methods: We performed a clinical analysis of the patients and specific allele PCR in DNA obtained from leukocytes. Results: Twelve of 14 patients presented with precocious puberty, one with cyclical vaginal bleeding and one with pathological bone fractures. Eight girls had polyostotic fibrous dysplasia, one had hyperthyroidism, four had pathological fractures, ten had ovarian cysts, six had breast hyperpigmentation and ten had "cafe au lait" skin lesions. We detected the R2O1H mutation in 10 of 14 patients. We found no difference in the severity of symptoms or in the age of presentation between the patients with and without the mutation. Conclusions: The R201H mutation can be detected in white blood cells, in approximately 70% of cases. Patients exhibit wide clinical variability with the same molecular defect. This suggests that tissues have different proportions of mutant cells (Rev Méd Chile 2001; 129: 1365-72)

Circulating concentrations of the high affinity growth hormone binding protein (GHBP) may be a marker of GH receptor density as well as GH sensiffvity. Goal: To determine values of GHBP for a normal Chilean pediatric population. Methods: We determined GHBP levels in 73 males and 73 females between 4 to 15.5 years and 4 to 16.8 years respectively, divided in 7 groups according to age and puberal status. Results: The population was normally distributed in weight, height and body mass index (BMI). GHBP activity increased up to Tanner IV in males and Tanner III in females, and decreased slightly thereafter in Tanner V and IV respectively. There was a significant difference between GHBP levels of preschool children and those found in Tanner II to V in both sexes (p<0.05). In adition, we found a positive correlation between GHBP vs weight, height and BMI (p<0.001) in males and females. Conclusion: The availability of this methodology allows us to establish the normative value of GHBP in our population and provides useful information to interpret GH circulating levels in children with growth disorders.(Rev Méd Chile 2001; 129: 382-9)

Recently, several groups have studied the influence of possible noxious elements present in the intrauterine environment which may favor the development of several diseases in the adult. There is evidence of an increased prevalence of some disorders in special risk groups of fetuses. In the small for gestational age patient, a form of "programming" may occur which produce metabolic changes in the fetus in response to malnutrition. There are several other associations described, but in most of them the precise pathogenic mechanisms involved have not been elucidated. In this article we present evidence of several disorders which develop in the adult and their relationship with conditions during fetal life. Finally, we offer some recommendations to diminish these risks (Rev Méd Chile 2001; 129: 307-15).

In a girl with primary hypothyroidism caused by a lingual tryroid gland and short stature starling of age 2 years, magnetic resonance showed pituitary enlargement suggestive of maroadenoma, but after a therapeutic trial with thyroid hormone pituitary size returned to normal. Long-strading primary hypothyroidism may produce images suggesting pituitary entargement and macrocidenoma. The therapeutic trial thyroid hormone con be useful in the defferential diagnosis amorng boath conditions. differential diagnosis among both conditions.

En una niña con hipotiroidismo primario debido a tiroides sublingual y talla baja desde los dos años de edad, la resonancia magnético mostró aumento del tamaño de la apófisis sugerente de macroadenoma, que después de una prueba terapéutica con hormona tiroidea recupero el aspecto normal. El hipotiroidismo primario crónico puede Producir aumenta de volumen hipofisiario indistinguible del causado por un macroadenoma en los exámenes por Imágenes. El tratamiento con hormona tiroidea permite el diagnostico diferencial entre ambas entidades.