Stress and the reproductive axis.

There exists a reciprocal relationship between the hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes, wherein the activation of one affects the function of the other and vice versa. For example, both testosterone and oestrogen modulate the response of the HPA axis, whereas activation of the stress axis, especially activation that is repeating or chronic, has an inhibitory effect upon oestrogen and testosterone secretion. Alterations in maternal care can produce significant effects on both HPG and HPA physiology, as well as behaviour in the offspring at adulthood. For example, changes in reproductive behaviour induced by altered maternal care may alter the expression of sex hormone receptors such as oestrogen receptor (ER)α that govern sexual behaviour, and may be particularly important in determining the sexual strategies utilised by females. Stress in adulthood continues to mediate HPG activity in females through activation of a sympathetic neural pathway originating in the hypothalamus and releasing norepinephrine into the ovary, which produces a noncyclic anovulatory ovary that develops cysts. In the opposite direction, sex differences and sex steroid hormones regulate the HPA axis. For example, although serotonin (5-HT) has a stimulatory effect on the HPA axis in humans and rodents that is mediated by the 5-HT1A receptor, only male rodents respond to 5-HT1A antagonism to show increased corticosterone responses to stress. Furthermore, oestrogen appears to decrease 5-HT1A receptor function at presynaptic sites, yet increases 5-HT1A receptor expression at postsynaptic sites. These mechanisms could explain the heightened stress HPA axis responses in females compared to males. Studies on female rhesus macaques show that chronic stress in socially subordinate female monkeys produces a distinct behavioural phenotype that is largely unaffected by oestrogen, a hyporesponsive HPA axis that is hypersensitive to the modulating effects of oestrogen, and changes in 5-HT1A receptor binding in the hippocampus and hypothalamus of social subordinate female monkeys that are restored or inverted by oestrogen replacement. This review summarises all of these studies, emphasising the profound effect that the interaction of the reproductive and stress axes may have on human reproductive health and emotional wellbeing.

Carcinoma diferenciado de tiroides (CDT) en niños y adolescentes: Evolución clínica y factores pronósticos / Differentiated thyroid carcinoma in children and adolescents: Clinial outcome and prognostic factors

Si bien la forma de presentación del CDT es más agresiva en la edad pediátrica que en los adultos, la tasa de sobrevida es superior al 90%.Objetivo: analizar retrospectivamente las características clínico-patológicas,la evolución y los factores pronósticos en pacientes prepuberales (PP) y puberales (P) con diagnostico de CDT controlados en nuestro servicio. Resultados se incluyeron 43 pacientes seguidos por un tiempo X (±DS) de 5.99 años(a) (3.57) a, rango 1 -14 a. El tratamiento consistió en tiroidectomía con vaciamiento ganglionar, Iodo131 y levotiroxina en dosis inhibitoria de TSH. Al diagnóstico: edad cronológica (EC) X (±DS)10.9 (3.84) a, rango: 4.7 -17a, relación femenino /masculino 2.9. Diecinueve PP y 24 P. El 53.5% (n:23) presentó nódulos confinados a la glándula con o sin extensión ganglionar y el 46.5% (n:20) tenia un estadío tumoral más avanzado con invasión local y metástasis (MTS) pulmonar. Treinta y ocho pacientes (88.4%) tenían MTS ganglionar cervical y 16(37.2%) MTS pulmonar. El grupo PP comparado con el P tenía EC significativamente menor X (±DS) 7.25 (2.03) a vs 13.83a (p <0.001), estadío tumoral más avanzado 84.2 vs16.8% (p<0.001) y mayor ocurrencia de MTS pulmonar 68.4 vs 12.5% (p<0.003). La sobrevida global fue de 92% y libre de enfermedad 78%.Las variables predictoras de persistencia de enfermedad más significativas fueron presencia de MTS pulmonar al diagnóstico y niveles séricos de tiroglobulina superiores a 8.5 ng/ml posterior al tratamiento inicial. Conclusión: el CDT pediátrico tiene una presentación agresiva especialmente en los pacientes prepuberales. El pediatra debería incorporar el examen clínico del cuello para realizar un diagnóstico y tratamiento precoz (AU)

Children-DTC has been found to behave differently than in adults. At diagnosis, children present in a more aggressive way. However the overall survival rates is greater than 90%. The aim of this study was to perform a retrospective analysis of clinicopathologycal features at diagnosis, evolution and prognostic factors for DTC in pre-pubertal (PP)and pubertal (P)children treated at our centre. Results: 43 CDT patients were included. Mean follow up was X (±DS) 5.99 (3.57) years (y) range: 1 -14 y. Treatment consisted on total thyroidectomy with lymph node dissection, radioiodine therapy, and TSH suppressive therapy with L-thyroxine. At diagnosis: chronological age (CA) was (±DS) :10.9 (3.84) y, range: 4.7 - 17y,sex: female/male ratio: 32/11,nineteen were PP and 24 P. Twentythree ( 53.5%) presented intrathyroidal nodes with or without lymph node MTS, Twenty patients (46.5%) had advanced disease, with adjacent tissue invasion and lung MTS. Thirty-eight patients (88.4%) had cervical lymph node MTS, 16 (37.2%) lung MTS.PP group had significant less CA X (±DS) 7.25 (2.03) y vs 13.83 (1.95)y (p <0.001),advanced tumor stage 84.2 vs16.8% (p<0.001) and more lung MTS occurrence 68.4 vs 12.5% (p<0.003). Global survival rate was 92% and disease free survival rate was 78%.Lung metastases (MTS) and serum thyroglobuline levels greater than 8.5 ng\ml post initial treatment were the most significant prognostic factor related to persistent disease. Conclusion: CDT had a more aggressive presentation in children; especially in PP children. Pediatricians should be aware of this in order to realize a precocious diagnosis and treatment (AU)

Evaluación de sensibilidad-especificidad de valores de 170H progesterona sérica, basales y post estímulo con ACTH, en función del análisis molecular del gen CYP21A2 en la deficiencia de 21-hidroxilasa no clásica / Evaluation of sensitivity and specificity of serum 170H progesterone values at baseline and post ACTH stimulation in the function of molecular analysis of the CYP21A2 gene in non-classic 21-hydroxilase deficiency

La forma no clásica, post natal, de la hiperplasia suprarrenal congénita tiene una incidencia de 1 en 1000 en la población general y afecta al 6% de las mujeres hirsutas. En este estudio se estableció la sensibilidad y la especificidad de la respuesta de los niveles séricos de 17-hidroxiprogesterona (17OHP4) al estímulo agudo con ACTH en 203 pacientes de ambos sexos, pre y post puberales, con hiperandrogenismo, en los cuales se analizó si tenían una alteración molecular del gen CYP21A2. Posteriormente al estudio molecular, los pacientes fueron clasificados en tres grupos de acuerdo al genotipo: Gr0, n=61: ningún alelo mutado (no portadores de mutación); Gr1, n=55: un alelo mutado (portadores) y Gr2, n=87: dos alelos mutados (afectados). Por análisis de regresión logística (curvas ROC) se compararon los valores basales del Gr2 vs Gr0 y se obtuvo un valor de 17OHP4 de 7,2 ng/ml con una sensibilidad del 83% y una especificidad del 85%. Se sugiere entonces que en los pacientes con este nivel basal no se debería realizar el test de ACTH, y habría que confirmar el diagnóstico con el estudio molecular. Los niveles 17OHP4 a los 60 minutos post estímulo con ACTH mayores a 20 ng/ml son confirmatorios del diagnóstico con 84% de sensibilidad y 88% de especificidad. No sería necesario entonces realizar estudios moleculares. Un valor de 15,6 ng/ml diferencia Gr2 de Gr0 con una sensibilidad del 89% y una especificidad del 95%. Este es un buen valor predictivo, pero el análisis molecular no debería obviarse en aquellos casos en los que exista una fuerte sospecha clínica. (AU)

The incidence of non classic congenital adrenal hyperplasia is 1:1000 in the general population and it is present in 6% of hirsute women. In this study, the sensitivity and specificity of serum 17-hydroxyprogesterone (17OHP4) response to acute ACTH stimulation was evaluated in 203 prepubertal and pubertal patients of the two sexes with hyperandrogenism, in whom the CYP21A2 gene was analyzed. After molecular analysis patients were divided in 3 groups according to genotype: Gr0, n=61, no mutated allele (no mutation carrier); Gr1, n=55, one mutated allele (carrier); and Gr2, n=81, two mutated alleles (affected patient). Using logistic regression analysis (ROC curves), basal values in Gr2 vs. Gr0 were compared and a cutoff value of 7.2 ng/ml was defined to separate groups, with 83% sensitivity and 85% specificity. It is suggested then that in patients with levels higher than 7,2 no ACTH test is necessary and molecular analysis is required to confirm diagnosis. Serum 17OHP4 values above 20 ng/ml 60 minutes after ACTH are confirmatory of diagnosis, with 84% sensitivity and 88% specificity. No molecular studies should be necessary. A 15.6 ng/ml cutoff value is able to differentiate Gr2 from Gr0, with 89% sensitivity and 95% specificity. It is a good predictive value, but carrying out molecular analysis is only advisable if clinical evidence is strong (AU)

Displasia septo-optica. Evaluación clínica, endocrinológica y neuro-radiológica. Seguimiento de 46 pacientes pediátricos / Septo-optic dysplasia. Clinical, endocrinological, and neuroradiological evaluation. Follow-up of 46 pediatric patients

La displasia septo-óptica (DSO) es una condición rara y altamente heterogénea, definida por la combinación de hipoplasia del nervio óptico (HNO), malformaciones cerebrales de la línea media, tales como aplasia/hipoplasia de septum pellucidum y cuerpo calloso, e insuficiencia hipotálamo-hipofisaria de grado variable. Se realizó un trabajo que tuvo como objetivo caracterizar la población de pacientes con diagnóstico de DSO seguidos en nuestro Hospital durante 7 años. Se incluyeron 46 pacientes (18 mujeres) que fueron divididos en 2 grupos, según tuviesen o no insuficiencia hipotálamo-hipofisaria (IHH). El 58.7% (n=27) presentó IHH de algún tipo, mientras que el 41.3% (n=19) no la presentó. En aquellos 19 pacientes con IHH se diagnosticaron deficiencia de GH y TSH (85.1%) y de ACTH (48.1%). La longitud corporal (mediana) del grupo con IHH fue más baja (p = 0,01) que la del grupo sin IHH, a pesar de que la edad fue menor a 2 años en todos los casos. Los pacientes fueron seguidos 1,3-8,3 años. Se observaron incidencias similares de agenesia del cuerpo calloso, del septum pellucidum, y ventriculomegalia, pero las alteraciones del desarrollo cortical se observaron con mayor frecuencia en los pacientes sin IHH. La ictericia neonatal, convulsiones y/o hipoglucemia, y micropene en neonatos y lactantes con DSO se presentaron en el subgrupo con IHH. El 58,7% de los pacientes con DSO presentaron algún grado de insuficiencia hipotálamo-hipofisaria. En la mayoría de los casos el diagnóstico de IHH no se realizó en el momento de aparición de los síntomas, sino más tardíamente en su seguimiento. En el 45% de los pacientes se evaluaron alteraciones radiológicas del SNC, específicamente en la región hipofisaria. Una fracción importante de las deficiencias de TSH/T4 (36,4%), GH (50%) y ACTH (23%) aparecieron mas tardíamente en el curso de la evolución. En 10 niños con déficit de hormona de crecimiento (2 tests farmacológicos sin respuesta) se realizó el tratamiento sustitutivo con rhGH (durante un periodo de 4±3 años), observándose una mejoría promedio de + 1,5 SDS en la talla de estos pacientes. En conclusión, la hipoplasia neonatal de nervios ópticos, asociada o no a ictericia e hipoglucemia, debe ser un signo de alarma para el diagnóstico de DSO, con riesgo de insuficiencia suprarrenal, shock y muerte, y puede requerir, por lo tanto, urgente tratamiento. Las deficiencias pueden aparecer en el curso de la evolución, a pesar del carácter congénito de la anomalía. Finalmente, se deben sustituir las deficiencias hormonales y tener presente que el tratamiento con rhGH puede mejorar la talla final en estos pacientes (AU)

Septo-optic dysplasia (SOD) is a rare and highly heterogeneous condition consisting of a combination of optic nerve hypoplasia (ONH), midline brain abnormalities, such as aplasia/hypoplasia of the septum pellucidum (ASP) and corpus callosum; and variable degree of hypoyalamo-pituitary insufficiency. The aim of this study was to characterize a population of SOD patients diagnosed and followed at the Garrahan Pediatric Hospital, from 1989 to 2006. We included 46 patients (18 females), that were divided into two groups according to the presence or absence of hypothalamic-pituitary insufficiency (IHH). Fifty nine% of SOD patients presented with IHH. GH and TSH deficiencies were diagnosed in 85.1% of IHH patients, while ACTH deficiency was found in 48.1%. Height (median) for the IHH group was shorter (p = 0,01) than for the group without IHH. Patients were followed for 1.3-8.3 years. Similar incidence of corpus callosum and/or septum pellucidum agenesis and ventriculomegaly were found in the two groups, but we observed more association with cortical developmental disorders in patients without IHH. In newborns, the association of ophthalmologic disorders and jaundice, seizures and/or hypoglycemia and micropene should frequently lead to the diagnosis of SOD and IHH. While 58,7% of DSO patients presented with hypothalamic-pituitary deficiency, only 45% of them showed sellar radiological abnormalities. Although SOD is a congenital disease, hormonal deficiencies may appear during follow-up. In 10 children with SOD and GH deficiency, rhGh treatment (for 4±3 years) improved height in 1.5 SDSs. In conclusion: in newborns with nerve optic hypoplasia, associated or not with jaundice, seizures and hypoglycaemia, the diagnosis of SOD and IHH should be considered. Treatment could be an emergency need because of risk of adrenal insufficiency and hypoglycemia (AU)

Hipotiroidismo central en pacientes con el síndrome de Prader-Willi durante los 2 primeros años de vida / Central hypothyroidism in patients with Prader-Willi syndrome during the first 2 years of life

Introducción. El síndrome de Prader-Willi SPW) es un trastorno genético causado por la pérdida de expresión de genes de origen paterno en la región cromosómica compleja 15q11-q13. El fenotipo clínico ha sido bien caracterizado, especialmente relacionado con la disfunción hipotalámica. Aunque entre 20 a 30% de los pacientes con SPW tienen hipotiroidismo central (HC), no ha sido bien definida la función tiroidea durante los dos primeros años de vida. Objetivo: evaluar la función hipotalámica-pituitaria-tiroidea en lactantes con SPW. Diseño del estudio: 18 pacientes con SPW entre 0,16 y 2 años de edad fueron incluídos en un estudio prospectivo. El diagnóstico de SPW se basó en los hallazgos clínicos y en el análisis molecular. Se calcularon los escores de desviacion estándar (SDS) de la T4 total (T), T4 libre (L), T3 y TSH en suero en todos los pacientes incluídos en el estudio. Resultados: En 14 de los 18 pacientes con SPW, se encontraron niveles de T4T y/o T4L menores a -2 SDS (44,4 y 55,5%, respectivamente), mientras que solamente en 1 paciente con SPW el nivel de T3 estaba por debajo de -2 SDS. Conclusión: Este estudio muestra que la incidencia de HC es alta en lactantes con SPW. Los pediatras deben tener en cuenta el diagnostico de HC en este período crítico de la acción de la hormona tiroidea en el desarrollo neurológico (AU)

Introduction. Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11- q13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism (CH) has been documented in 20 to 30% of PWS patients, thyroid function has not been well characterized during the first 2 years of life. Objective: to evaluate hypothalamic-pituitary-thyroid function in infant PWS patients. Study design: Eighteen PWS patients, aged 0.16 to 2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and TSH standard deviation scores (SDS) were calculated in all PWS patients included in the study. Results: In 14 out of 18 PWS patients, serum TT4 and/or FT4 levels less than -2 SDS ( 44.4 and 55.5 %, respectively) were found, while in only 1 PWS patient serum T3 levels was below -2 SDS. Conclusion: This study shows that there is a high incidence of CH in infant PWS patients. Pediatricians should be aware of this diagnosis in this critical period of thyroid hormone action on neurological development (AU)

Tumores del sistema nervioso central de localización selar y supraselar. Alteraciones neuro-oftalmológicas y de la función endocrina al diagnóstico / Sellar and suprasellar central nervous system tumors. Neuro-ophthalmological and endocrine function impairment at diagnosis

Los tumores (Tu) del SNC constituyen la segunda enfermedad oncológica en edad pediátrica, con una incidencia referida aproximada que oscila entre el 10 y 15%. En 309 pacientes con tumores selares y supraselares, seguidos durante 15 años, se evaluó en función de los distintos oncotipos tumorales, síntomas iniciales y alteraciones endocrinológicas previas al inicio del tratamiento. De ellos, 227 pacientes presentaron el tumor a edad prepuberal. Los oncotipos tumorales más frecuentes fueron craneofaringioma (CRA), glioma (GLIA) y tumor de células germinales (GERM). También, se encontró una mayor incidencia de presentación en varones. En edad puberal (n:92), el oncotipo tumoral más frecuente fue adenoma hipofisario (ADENO), seguido de GLIA y CRA. En este ultimo oncotipo tumoral, y, a diferencia del grupo prepuberal, su incidencia fue significativamente mayor en niñas. Aproximadamente 90% de los pacientes tuvieron anormalidades neuro-oftalmológicas (hipertensión craneal, dolores de cabeza, vómitos y pérdida progresiva de la visión) como uno de los signos y/o síntomas iniciales. Alteraciones clínicas endocrinológicas como baja talla, velocidad de crecimiento anormal, diabetes insípida y alteraciones del tempo puberal son frecuentes en estos pacientes y están habitualmente asociadas con las alteraciones clínico-neuro-oftalmológicas como las ya mencionadas. No obstante, la mayoría de los tumores del SNC localizados en la línea media suelen ser diagnosticados por manifestaciones neuro-oftalmológicas. Los resultados del estudio muestran alteración de la función endócrina al diagnóstico del Tu. Se concluye que en todo paciente con crecimiento lento o baja talla, así como también signos clínicos que orienten a un diagnóstico de pubertad precoz y/o retardada, el pediatra debe incluir dentro de los diagnósticos diferenciales, el diagnóstico del tumor selar o supraselar. La morbilidad aumenta frecuentemente luego de la cirugía (AU)

During the last 15 years, 309 patients with tumors of the sellar and suprasellar areas of CNS were followed in our Hospital (Endocrine Service). Tumor oncotype, initial symptoms and endocrine disturbances before any treatment was started are presented. In 227 patients, the tumor was diagnosed at prepubertal age. In this group, the most frequent tumoral oncotypes were craniopharyngioma (CRA), glial tumors (GLIA) and germ cells tumors (GERM). The incidence was higher in boys. At pubertal age (n:92), the most frequent tumoral oncotype was pituitary adenoma (ADENO), followed by GLIA and CRA. In the latter, and different from the prepubertal group, the incidence was significantly higher in girls. Approximately 90% of patients had neuro-ophtalmological abnormalities (cranial hypertension, headaches, vomits, and progressive loss of vision) as one of the initial signs and/or symptoms. Clinical endocrine disorders, such as short stature, low growth velocity, diabetes insipidus, and alterations in pubertal "tempo" are frequent in these patients and are often associated with the neuro-ophtalmological abnormalities mentioned above. This clinical symptomatology has to alert the medical team to discard the presence of a CNS tumor at the sellar and/or suprasellar level. We conclude that tumors of the SNC localized in the midline, have potential capacity to provoke abnormalities in endocrine function. Morbidity is often increased after surgery (AU)

Evaluación de la talla final y sobrevida libre de eventos en pacientes sobrevivientes de meduloblastoma con deficiencia de hormona de crecimiento, tratados o no con hormona de crecimiento biosintética recombinante humana en la niñez. Comparación con pacientes con craneofaringioma tratados con rhGH / Evaluation of final height and event-free survival in medulloblastoma patients with growth hormone deficiency with and without biosynthetic recombinant human growth hormone treatment in childhood

Introduccion: La deficiencia de GH (DGH) y la radioterapia espinal (RE) han sido implicadas en la etiología de la talla adulta (TA) baja en los sobrevivientes de meduloblastoma en la niñez. Sin embargo la dinámica del crecimiento luego del diagnóstico tumoral y la efectividad de la Hormona de crecimiento biosintética recombinante humana (rhGH) sobre la TA en comparación con sobrevivientes no tratados con rhGH no han sido reportadas. Objetivo. Evaluación de la talla (T) SDS (SDST) desde el diagnóstico del meduloblastoma y el efecto de la rhGH en pacientes con DGH comparando con pacientes no tratados con rhGH y con pacientes con craniofaringioma y DGH, tratados con rhGH. Analizar si había alguna diferencia en la sobrevida libre de eventos en los pacientes con meduloblastoma al ser tratados con rhGH. Material Clínico y Métodos. Catorce pacientes con meduloblastoma recibieron rhGH hasta la TA, grupo meduloblastoma tratado con GH (GrMGH). Diecinueve pacientes rechazaron la terapia con rhGH, grupo meduloblastoma control (GrMC). Se midieron la talla parada (T) y la talla sentada (Tsent). Ocho pacientes con craneofaringioma recibieron rhGH hasta la TA (GrCra). Se realizó seguimiento de 72 pacientes con meduloblastoma, 20 con tratamiento con rhGH. Resultados. En GrMGH, la media±DS SDST disminuyó de 0.09±0.63 al diagnóstico del tumor a -1.38±0.91 al diagnóstico del DGH, y a -1.90±0.72 al comienzo de rhGH, p<0.01, pero se mantuvo sin cambios durante el tratamiento con rhGH (TA -2.12±0.55). En GrMC la SDST (-0.25±0.88) no fue diferente de GrMGH al diagnóstico del tumor, pero fue -3.40±0.88 a la TA, significativamente menor que en GrMGH, p=0.001. La Tsent SDS a la TA (-4.56±0.82) fue significativamente menor que al comienzo de rhGH (-2.86±0.75), p=0.003, y no fue diferente de GrMC (-4.85±1.77). El GrCra mostró la mayor ganancia de talla (GT = TA-SDSTinicial), p< 0.007, y la menor pérdida de talla (PT= Tblanco - TA), p < 0.0001. Conclusión. El tratamiento con rhGH mejora la TA en sobrevivientes de meduloblastoma en la niñez con DGH, pero no el crecimiento espinal. Las características del crecimiento y la respuesta a rhGH son diferentes en GrMGH y en GrCra, mientras que el primer grupo sólo pudo mantener la talla relativa, el segundo mostró una franca recuperación del crecimiento. Además no hubo diferencias en la sobrevida libre de eventos en los pacientes con meduloblastoma con y sin tratamiento con rhGH (AU)

Background. GH deficiency (GHD) and spine irradiation (SI) have been implicated in the mechanism of reduced adult height (AH) in childhood survivors of medulloblastoma. However, growth dynamics after tumor diagnosis and the effectiveness of (rhGH) Recombinant human Growth Hormone on AH in comparison with rhGH-untreated survivors has not been reported. Aim. Follow up of height (H) SDS (HSDS) after diagnosis of meduloblastoma, and the effect of rhGH in GHD meduloblastoma patients. Comparison with GH-untreated GHD meduloblastoma patients and with GHD craniopharyngioma patients treated with rhGH. To evaluate event free survival in medulloblastoma patiens treated with rhGH. Clinical Material and Methods. Fourteen survivors of medulloblastoma received rhGH treatment until AH, Medulloblastoma GH-treated group (MGHGr). Nineteen patients refused rhGH therapy, GH-untreated Control Medulloblastoma Group, (MCGr). Standing H and sitting H (SitH) were measured. Eight patients with craniopharyngioma received rhGH treatment until AH (CraGr). 72 patients with medulloblastoma were followed up, 20 with rhGH. Results. In MGHGr, mean±SD HSDS decreased from 0.09±0.63 at tumor diagnosis to -1.38±0.91 at diagnosis of GHD, and to -1.90±0.72 at the onset of rhGH, p<0.01, but it remained unchanged during rhGH (AH -2.12±0.55). MCGr HSDS (- 0.25±0.88) was not different from MGHGr at tumor diagnosis, but it was -3.40 ± 0.88 at AH, significantly lower than in MGHGr, p=0.001. SitH SDS at AH (-4.56±0.82) was significantly lower than at the onset of rhGH (-2.86±0.75), p=0.003, and it was not different from MCGr (-4.85 ± 1.77). CraGr showed the highest height SDS gain (HG = FH ­ startHSDS), p<0.007, and the lowest height lost (HL = targetH - AH), p< 0.0001. Conclusions. rhGH treatment improves AH in GH-deficient childhood medulloblastoma survivors but not spinal growth. Growth pattern and response to rhGH differed in MGHGr and CraGR, while the former just could maintain height SDS under treatment, the latter showed a clear catch up growth. There wasn't any difference in the event free survival in medulloblastoma patients with or without rhGH (AU)

Gender-dependent effects of early maternal separation and variable chronic stress on vasopressinergic activity and glucocorticoid receptor expression in adult rats.

The aim of the present study was to investigate the influence of early maternal separation on Fos, arginine vasopressin (AVP) and glucocorticoid receptor (GR) expression in the medial parvocellular portion of the paraventricular hypothalamic nucleus (PaMP), and GR expression in the hippocampus of adult male and female rats subjected to variable chronic stress (VCS). Male and female Wistar rats were isolated 4.5 h daily, during the first 3 weeks of life. At 48 days of age, the rats were exposed to VCS. Nonmaternally separated (NMS) females had a higher number of activated AVP neurons than NMS male rats. Maternally separated (MS) females subjected to VCS also showed a higher number of Fos/AVP double-labeled neurons than males with the same treatment. Males and females subjected to early maternal separation and VCS, compared with the MS animals, showed a decrease in the expression of GR in the PaMP. As regards GR expression in the hippocampus, MS animals subjected to VCS as adults, both males and females, showed an increase in GR expression in the subfields CA1, CA2 and CA3. The increase in AVP-immunoreactive neurons coexpressing Fos in response to stress in females exposed to early maternal separation suggests that perhaps early life stress results in a more reactive neuroendocrine stress response in females. Furthermore, our results demonstrate that the different anatomical levels of the hypothalamic-pituitary-adrenal axis have different roles related to its stress response and support the evidence of regional specificity in GR regulation.

Effectiveness of rhGH treatment on adult height in GH-deficient childhood survivors of medulloblastoma.

BACKGROUND: GH deficiency (GHD) and spine irradiation (SI) have been implicated in the mechanism of reduced adult height (AH) in childhood survivors of medulloblastoma. However, growth dynamics after tumor diagnosis and the effectiveness of rhGH on AH in comparison with rhGH-untreated survivors have not been reported. AIM: To follow height (H) SDS (HSDS) since tumor diagnosis and the effect of rhGH in GHD patients, comparing with GH-untreated GHD patients. METHODS: 14 patients received rhGH treatment until AH (medulloblastoma GH-treated group, MGHGr). 19 patients refused rhGH therapy (GH-untreated control medulloblastoma group, MCGr). Standing H and sitting H (SitH) were measured. RESULTS: In MGHGr, mean +/- SD HSDS decreased from 0.09 +/- 0.63 at tumor diagnosis to -1.38 +/- 0.91 at diagnosis of GHD, and to -1.90 +/- 0.72 at the onset of rhGH, p < 0.01, but it remained unchanged during rhGH (AH -2.12 +/- 0.55). MCGr HSDS (-0.25 +/- 0.88) was not different from MGHGr at tumor diagnosis, but it was -3.40 +/- 0.88 at AH, significantly lower than in MGHGr, p = 0.001. SitH SDS at AH (-4.56 +/- 0.82) was significantly lower than at the onset of rhGH (-2.86 +/- 0.75), p = 0.003, and it was not different from MCGr (-4.85 +/- 1.77). CONCLUSIONS: rhGH treatment improves AH in GH-deficient childhood medulloblastoma survivors but not spinal growth.

Genetic and clinical spectrum of aromatase deficiency in infancy, childhood and adolescence.

INTRODUCTION: cP450aromatase deficiency provides clues for the understanding of the role of aromatase in prepubertal and pubertal human health and disease. Placental aromatization of androgens protects the female fetus against the virilizing action of fetal androgens. After birth, the dual effect of aromatase deficiency, excessive androgens, and insufficient estrogens is responsible for a variable clinical picture. Nineteen cases of aromatase gene (CYP19) deficiency have been reported. PHENOTYPE: Phenotype is dependent on sex and age. In newborns, aromatase deficiency should be considered in the etiology of 46,XX DSD, after ruling out congenital adrenal hyperplasia. In prepubertal aromatase deficient girls, high levels of ovarian androgens and gonadotropins facilitate the formation of ovarian cysts. Bone mineralization can be affected and bone aging is delayed. In pubertal girls, there is poor sexual development and abnormal virilization. The phenotype may be variable according to enzyme activity level. Insulin sensitivity may be abnormal in both men and women. Finally, aromatase might also play a role in the regulation of testicular cell mass in the newborn testis. CONCLUSION: Adequate interpretation of clinical data should lead to the analysis of the CYP19 gene for diagnostic confirmation and implementation of appropriate management.

Serum IGF-I and IGFBP-3 reference values from a chemiluminescent assay in normal children and adolescents of hispanic and italian origin: presence of sexual dimorphism in IGF-I values.

Serum IGF-I and IGFBP-3 assays are used to monitor rhGH treatment. Some discrepancies in results obtained by means of different assays have been reported. The aim of this study was to establish normal ranges for circulating IGF-I and IGFBP-3 in children and adolescents of Hispanic and Italian origin. Circulating levels of IGF-I and IGFBP-3 were measured in 169 Hispanic and Italian prepubertal children and 66 adolescents of both sexes, using a chemiluminescent assay. Serum levels of IGF-I and IGFBP-3 increased from early childhood into adolescence. After pubertal peaks of IGF-I and IGFBP-3, slight decreases were observed with increasing age. Furthermore, serum IGF-I levels were significantly higher in girls than in boys, suggesting a sexual dimorphism in serum IGF-I values in late prepuberty and early puberty. Differences in IGF-I and IGFBP-3 absolute values between our study and previous studies suggest the need to establish reference ranges for each ethnic group.