Pubertad precoz periférica por tumor ovárico de las células de la granulosa juvenil: con manifestaciones iso y heterosexuales en una niña de 6 años / Precocious puberty in a six years old girl caused by a juvenile granulosa cell ovaric tumor: report of one case

A six years old girl consulted due to mammary development. On physical examination, clitoris enlargement and a tumor localized in the abdominal-pelvic region were observed. Hormonal study disclosed elevated testosterone and estradiol levels. On exploratory laparotomy, a right ovarian tumor was observed and a right salpingo-oophorectomy was performed. The contemporary biopsy informed a disgerminoma, leading to a surgical staging of the tumor. The definitive pathological diagnosis was a juvenile granular cell tumor, limited to the ovary. In the postoperative period, estradiol and testosterone levels returned to normal values and the pseudopuberty reverted. The patient did not receive adjuvant treatment and after three years of follow up, there is no evidence of tumor recidivism

Estudio clínico molecular de pacientes chilenas con síndrome de McCune-Albright / Clinical and molecular study of Chilean patients with McCune-Albright Syndrome

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 per cent of cases. Patients exhibit wide clinical variability with the same molecular defect. This suggests that tissues have different proportions of mutant cells

Medición de 17-OH progesterona sanguínea en recién nacidos chilenos: antecedentes para implementar un programa de detección neonatal de hiperplasia suprarrenal congénita / 17 OH progesterone measurement in blood of chilean newborns: as a background to start a congenital adrenal hyperplasia screening program

Background: The early diagnosis and therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can prevent adrenal crises and erroneous gender assignment in affected newborns. To achieve this goal neonatal mass-screening programs have been developed, measuring blood 17 alpha-hydroxyprogesterone (17OHP). In Chile there is no experience with this type of screening. Aim: To develop a method for measuring 17OHP in filter paper blood specimens. To obtain reference ranges and determine neonatal 17OHP threshold levels according to gestational age and birth weight. To analyze factors affecting the cost-efficiency ratio and suggest recommendations for the organization of a neonatal screening program for CAH in Chile. Material and methods: Nine hundred twenty two newborns were studied. 17OHP was measured using double antibody radioimmunoassay in filter paper blood samples obtained 48 h after birth. Reference ranges were determined according to gestational age and birth weight and a cutoff point of 25 ng/ml was established. Results: Seventeen newborns had 17OHP over the cutoff value. They were assessed by a pediatric endocrinologist and in none of them, CAH was confirmed. Therefore the false positive rate of the determination was 1.8 percent. Among these newborns with elevated 17OHP, 66 percent had a birth weight below 1.5 kg and 5.8 percent, a birth weight between 1.5 and 2.5 kg. The cost per reported result was US $ l. Timing of the recall was between the 3 and 10 days of life. No newborn missed the follow-up. Discussion: To increase the cost-efficiency ratio of an eventual neonatal screening program, newborns with birth weights below 1.5 kg should be excluded and cutoff points should be defined according to birth weight

Recambio óseo en nodrizas adolescentes: evaluación al término de la gestación, lactancia y postdestete / Bone turnover in lactating teenagers: assessment at the end of pregnancy during and after the breast feeding period

Background: There is paucity of information about bone metabolism during pregnancy or breast feeding in teenagers. Aim: To study bone turnover at the end of pregnancy and during breast feeding in teenagers and correlate it with environmental, hormonal or nutritional variables. Subjects and methods: Thirty teenagers during their breast feeding period after a first pregnancy and 30 nulliparous girls matched for age, age of menarche and body mass index were assessed three weeks after delivery (period 1), at six months of breast feeding (period 2) and one year after the lactating period (period 3). Calcium intake and plasma calcium, phosphorus, alkaline phosphatases, parathormone, estradiol and prolactin were measured. Calcium, creatinine and hydroxyproline were also measured in a morning urine sample. Results: Lactating and control girls were aged 16.3ñ0.8 and 16.1ñ0.7 years old respectively. Calcium intake in lactating and control girls was 798ñ421 and 640ñ346 g/day respectively in period 1, 612ñ352 and 592ñ309 mg/day in period 2 and 495ñ180 and 456ñ157 g/day in period 3. During periods 1 and 2, lactating girls had higher alkaline phosphatases (161ñ37 compared to 119ñ28 U/l and 149ñ37 compared to 106ñ23 U/l), parathormone (4.3ñ2.6 compared to 2.8ñ0.8 ng/dl and 3.6ñ1.6 compared to 3.0ñ0.9 ng/dl) and urinary hydroxyproline (95ñ16 compared to 63ñ15 mg/g creatinine and 84ñ19 compared to 59ñ15 mg/g creatinine). No differences were observed in period 3. No correlation between bone turnover variables, body mass index or hormonal parameters, was observed. Conclusions: In teenagers, there is an increase in bone turnover at the end of pregnancy, that persists during the lactating period. These changes are not related to nutritional or hormonal variables

Diagnóstico molecular de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa, variedad perdedora de sal, en población chilena / Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by deficit of 21-hydroxylase, in the Chilean population

Twenty five patients with salt wasting congenital adrenal hyperplasia, that had 17-hydroxyprogesterone levels above 30 ng/ml, were studied. In all patients, a polymerase chain reaction (PCR) with selective primers was done with extracted genomic DNA, to amplify the active gene and specific primers for normal or mutated alleles of 50 chromosomes of the 25 patients. The higher frequency affected the ASIn2 in 26 percent of cases, followed by mutations Arg357Trp in 22 percent of cases and Gln319Stop in 12 percent and deletion in 12 percent. The frequent genotypes were homozygosity for ASIn2 (16 percent), homozygosity for Arg357Trp (12 percent) and the homozygote deletion of the gene in 12 percent. The most frequent mechanisms of genetic deficiency of 21-hydroxylase were the mutations ASIn2 Arg357Trp. This type of studies allows prenatal diagnosis and genetics counseling

Macroprolactinoma en adolescentes: respuesta al tratamiento con bromocriptina / Macroprolactinoma in adolescents: response to the bromocriptine treatment

Los macroprolactinomas son raros en niños y adolescentes. En adultos el tratamiento con bromocriptina (BC) ha sido exitoso. Existe escasa información en relación a su uso en edad pediátrica. Se describen tres casos de adolescentes con macroprolactinomas, tratados con bromocriptina, dos mujeres de 14 y 17,6 años con amenorrea, galactorrea, cefalea y un varón de 18 años con retardo del crecimiento y el desarrollo puberal, hipotiroidismo y déficit de hormona de crecimiento. Todos tenían hiperprolactinemia (>150 ng/ml) y tumor selar mayor de 10 mm. Después de tratamiento con bromocriptina se consiguió en dos de ellos prolactinemia normal y desaparición completa del tumor. Una de las niñas respondió sólo parcialmente al tratamiento. La bromocriptina es pues un tratamiento efectivo, aún en pacientes con deterioro del campo visual e hipopituitarismo y como en adultos, debería ser considerada el tratamiento de primera elección en adolescentes con macroprolactinomas

Telarquia prematura: aumento de la actividad estrogénica total en el plasma / Premature thelarche: increased of total estrogenic activity in the serum

Con el propósito de estudiar las causas de la telarquia prematura, se comparó el perfil hormonal y las características de los genitales internos mediante ultrasonografía pelvians en 41 niñas afectadas, de 21,15 ñ 9,74 meses de edad y e 31 controles de la misma edad y nivel socioeconómico y se buscó contaminación de los alimentos con zearalenona y dietilbestrol por cromatografía en capa delgada. La actividad estrogénica total en el plasma de las niñas, así como plasma y tejidos de pollo, se midió por el método de radiorreceptor. Las concentraciones basales de LH, FSH, prolactina y estradiol eran similares en pacientes y controles. La actividad estrogénica total fue significativamente mayor en las niñas con telarquia (201 ñ 102 vs 78 ñ 20 pg E2 equivalente) y descendió a niveles similares que en los controles (75 ñ 8 pg E2) al desaparecer la telarquia. La respuesta a LHRH en pacientes con telarquia fue mayor para FSH (28,7 ñ 17,5 Uµ/ml) que para LH (5,01 ñ 2,7 Uµ/ml). El tamaño del útero y la maduración ósea fueron similares en ambos grupos, pero el volumen ovárico medio fue mayor en pacientes con telarquia. No se detectaron contaminantes exógenos en la sangre de las niñasy los tejidos de 25 pollos. La actividad estrogénica en el plasma de las aves cumplía las recomendaciones internacionales (FAO). La respuesta de FSH al factor liberador, el mayor volumen ovárico y el aumento de la actividad estrogénica sugieren activación parcial del eje hipotálamo-hipofisiario-gonadal de predominio FSH en las niñas con telarquia prematura

Telarquia prematura / Premature thelarche

Se examinaron 460 niñas sanas de 6 a 36 meses de edad, de servicios públicos y consultas privadas de salud en busca de telarquia prematura. En 75 (14,1 por ciento) se encontró tejido mamario palpable de 10 mm de diámetro o más. No se observó diferencias significativas en la prevalencia entre niñas de diferentes procedencias. Los antecedentes de 53 niñas con telarquia prematura, ninguna con antecedentes de haber recibido preparados hormonales, incluidas las respuestas obtenidas por encuesta a sus madres, fueron comparados con los de 47 sanas sin telarquia. No hubo diferencias significativas en las características del embarazo, parto, período neonatal, historia médica y de nutrición entre pacientes y controles. En 26 casos la telarquia prematura representaba persistencia de telarquia neonatal. El crecimiento y la edad ósea de las pacientes con telarquia prematura eran apropiados para su edad cronológica. 28 pacientes fueron seguidas por 5 a 15 meses, 21 (75 por ciento) mostraron disminución del tejido mamario, 5 (18 por ciento) su desaparición y 2 (1 por ciento) un aumento, pero sin otros signos de pubertad. La telarquia prematura es una condición benigna, que tiende a desaparecer en forma espontánea y su causa no parece relacionada con contaminación hormonal de los alimentos. Si bien no es posible excluir el rol de otros contaminantes ambientales, la telarquia prematura puede ser una variante del desarrollo normal en niñas menores