ABSTRACT
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)
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Body Height/drug effects , Body Height/radiation effects , Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Craniopharyngioma/radiotherapy , Medulloblastoma/complications , Medulloblastoma/drug therapy , Medulloblastoma/radiotherapy , Survival , Cohort Studies , Treatment OutcomeABSTRACT
BACKGROUND: Growth deficit has been reported as a frequent complication of the treatment of acute lymphoblastic leukemia (ALL). PROCEDURE: Longitudinal analysis of the growth of 129 children, from a total of 351 cases diagnosed between 1987 and 1994 in Brazil, was determined. Height data were converted into standard deviation Z scores. Only girls younger than 10 and boys younger than 12 years old at diagnosis were included. Patients were treated according to a German BFM-83 based protocol. Fifty-eight children received 18 Gy cranial irradiation, four 12 Gy, and two 24 Gy. Patients were aggregated into five non-excluding groups according to availability of height data at diagnosis, during the treatment, at the end of it, and several years after; 35 children reached their final height. RESULTS: Height deficit at the end of the therapeutic treatment was evident (P < 0.0001). Catch-up occurred 1 year after stopping treatment (P = 0.016). At the last follow-up, over 5 years after the end of treatment (n = 83) or at final height (n = 35), impressive height deficits were recorded (P < 0.0001 for both end points). Multivariate analysis demonstrated that growth impairment was more severe in children younger than 4 years at diagnosis and in those who received cranial irradiation. No significant effect of gender was observed. Children who were treated solely with chemotherapy also had significant height loss. CONCLUSIONS: Treatment of ALL in children is associated with growth deficit during the treatment and several years after it, affecting the final height negatively, particularly in patients younger than 4 and in those who received cranial irradiation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cranial Irradiation/adverse effects , Growth Disorders/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Age Factors , Body Height/drug effects , Body Height/radiation effects , Brazil , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
AIM: The aim of this study was to evaluate the positive predictive value of two growth hormone stimulation tests (insulin-induced hypoglycemia and clonidine) for stature below percentile 10 in patients treated for acute lymphoblastic leukemia in childhood. METHODS: The study population was a cohort of 30 patients (aged 14.1+/-2.9 years; 20 male) treated for acute lymphoblastic leukemia during childhood and then examined after insulin-induced hypoglycemia (30 patients) and clonidine (16 patients) tests. The follow-up time was 7.7+/-2.8 years since treatment and 2.3+/-1.3 years after administration of the tests. RESULTS: In the last evaluation, 12 patients (40%) were below and 18 (60%) were above percentile 10. The insulin-induced hypoglycemia test response was: 9 patients (30%) had growth hormone peak <5 ng/mL and 19 (63.3%) <7 ng/mL. The clonidine test response was: 7 patients had growth hormone peak <5 ng/mL and 8 (50%) <7 ng/mL. For stature below of the percentile 10, the positive predictive values of insulin-induced hypoglycemia test (33%) and clonidine (28%) were low when growth hormone peak <5 ng/mL was considered; however, when growth hormone peak <7 ng/mL was considered, the positive predictive values were 83% and 50% for the insulin-induced hypoglycemia and clonidine tests, respectively. CONCLUSIONS: In patients treated for acute lymphoblastic leukemia in childhood, the positive predictive values for statural deficit of both tests were low, except for the insulin-induced hypoglycemia test when a growth hormone peak <7 ng/mL was considered.
Subject(s)
Body Height/drug effects , Body Height/radiation effects , Human Growth Hormone/deficiency , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adrenergic alpha-Agonists , Child , Child, Preschool , Clonidine , Cohort Studies , Drug Therapy, Combination , Female , Human Growth Hormone/blood , Humans , Hypoglycemic Agents , Insulin , Male , Predictive Value of TestsABSTRACT
UNLABELLED: Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment. PATIENTS AND METHOD: The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy), and group C underwent chemotherapy plus radiotherapy (24 Gy). Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging. RESULTS: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau) between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy). The final predicted height (Bayley-Pinneau) was significantly less (P = 0.0071) in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis. CONCLUSION: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.
Subject(s)
Growth , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Puberty , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Body Height/drug effects , Body Height/radiation effects , Child , Endocrine Glands/drug effects , Endocrine Glands/radiation effects , Female , Growth/drug effects , Growth/radiation effects , Humans , Male , Puberty/drug effects , Puberty/radiation effects , Radiotherapy/adverse effects , Radiotherapy DosageABSTRACT
Nos últimos 20 anos, após o tratamento de pacientes portadores de leucemia linfoblástica aguda, com quimioterapia e radioterapia, houve melhora na taxa de sobrevivência e cura em torno de 70 por cento. Crianças portadoras da doença foram envolvidas em protocolos de tratamento internacionais que visavam melhorar a sobrevida e minimizar os graves e irreversíveis efeitos tardios. A nossa unidade utiliza o protocolo internacional GBTLI LLA-85 e 90, com as drogas metrotexate, citosina, arabinoside, dexametasona e radioterapia .Entretanto, estes tratamentos podem causar insuficiências gonadais e prejuízo no crescimento. PACIENTES E MÉTODO: Os autores analisaram 20 crianças fora de terapia a fim de determinar o papel das várias doses de radioterapia sobre alterações endocrinológicas. Foram divididos em três grupos baseados na profilaxia do sistema nervoso central: o grupo A foi submetido à quimioterapia, o grupo B à quimioterapia mias radioterapia (18Gy) e o grupo C à quimioterapia mais radioterapia (24 Gy). Foram avaliadas as concentrações séricas de LH, FSH, GH e testosterona. Os estudos de imagem incluiram idade óssea, ultrassonografia pélvica, escrotal e ressonância nuclear magnética do crânio. RESULTADOS: Houve diferenças significativas nas respostas do hormônio de crescimento e prejuízo na estatura final (Bayley-Pinneau) entre os dois grupos irradiados e o grupo que não foi irradiado, mas não houve diferenças quando se compararam as doses de radiação utilizadas (18 ou 24 Gy). A previsão da altura final (Bayley-Pinneau) foi menor (p= 0,0071) nos dois grupos tratados com radioterapia. Duas meninas apresentaram puberdade precoce e um menino teve atraso puberal associado a calcificação do epidídimo. CONCLUSÃO: A radioterapia é responsável por efeitos colaterais especialmente quanto ao crescimento e puberdade.
Subject(s)
Adolescent , Child , Female , Humans , Male , Growth , Puberty , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Body Height/drug effects , Body Height/radiation effects , Endocrine Glands/drug effects , Endocrine Glands/radiation effects , Growth/drug effects , Growth/radiation effects , Puberty/drug effects , Puberty/radiation effects , Radiotherapy Dosage , Radiotherapy/adverse effectsABSTRACT
The Antarctic ozone hole and a general depletion of the stratospheric ozone layer cause increased levels of ultraviolet-B solar radiation (UV-B) over Tierra del Fuego, the southernmost tip of South America. For three consecutive growing seasons (1997-2000), we studied the biological impacts (morphology, physiology, demography and phenology) of natural UV-B radiation on a perennial Salicornia ambigua Michx. community in San Sebastian Bay (53 degrees S and 68 degrees W), Tierra del Fuego, Argentina. This is the first UV-B screening experiment on a subantarctic halophytic community. The shortwave UV-B spectrum (280 to 320 nm) was excluded by covering plots with UV-B blocking film (Mylar). These plots were compared to controls covered with UV-B transparent (Aclar) plastic screens, and unscreened plots. Shoot length in Salicornia was not affected by UV-B. Exposure to natural UV-B reduced biomass and density (by 17% and 38%, respectively). Concentration of UV-shielding pigments and cuticle thickness were both significantly higher (25-48% and 21-40%, respectively) in plants receiving ambient UV-B. The increase in cuticle thickness persisted throughout the growing season, whereas pigment concentration was higher at the beginning of the growing season. Also, the number of dead shoots was higher in plants exposed to UV-B. At the end of the growing season (March) shoot mortality was higher in plants exposed to ambient UV-B, and post-flowering senescence was 30 days earlier. Slight changes in the relative composition of Salicornia to Puccinellia were seen. The reduction observed in Salicornia shoot density under ambient UV-B was cumulative over time; 23% in the first growing-season, rising to 38% by the third growing-season. A similar incremental increase in pigment absorption at 305 nm was seen; 25% in the first and 48% in the third growing season.
Subject(s)
Chenopodiaceae/growth & development , Chenopodiaceae/radiation effects , Ultraviolet Rays , Argentina , Biomass , Body Height/radiation effects , Body Weight/radiation effects , Flowers/radiation effects , Time FactorsABSTRACT
Craniospinal radiation therapy for treatment of brain tumors may result in growth hormone (GH) insufficiency with resultant linear growth retardation, one of the most common complications. We report the case of a 10-year-old boy presenting headache associated to vertigo, nausea and vomiting. A CT scan showed an homogeneous mass in the left cerebelar hemisphere, that was surgically removed. The histopathological examination revealed medulloblastoma and the patient was submitted to craniospinal radiation. He did not present tumor recurrence nor neurological or cognitive deficits during 4 years, but evolved to short stature due to GH deficiency. Nowadays, he is being receiving GH 0,1 U/kg/day and has presented 4cm stature increment after 6 months. The present case highlights the importance in carefully monitoring of children after cranial radiation for oncologic treatment, because they may develop hormonal deficiencies, that can be successfully replaced.
Subject(s)
Cerebellar Neoplasms/radiotherapy , Growth Disorders/etiology , Growth Hormone/radiation effects , Medulloblastoma/radiotherapy , Body Height/radiation effects , Cerebellar Neoplasms/surgery , Child , Cranial Irradiation/adverse effects , Growth Disorders/drug therapy , Growth Hormone/deficiency , Growth Hormone/therapeutic use , Humans , Male , Medulloblastoma/surgeryABSTRACT
OBJECTIVE: Optic pathway tumors decrease adult height by central precocious puberty (PP) or hypothalamic-pituitary disorders, particularly growth hormone (GH) deficiency caused by the tumor, management of the tumor, or associated neurofibromatosis 1. The objective of this study was to evaluate the respective roles of these factors on disorders and adult height. STUDY DESIGN: Thirty-five patients with optic pathway tumors diagnosed at 6.4 +/- 0.6 years treated by cranial irradiation (30-56 Gy) reached adult height after treatment with GH alone (n = 16), gonadotropin hormone-releasing hormone analogue alone (n = 2), or both (n = 16). RESULTS: Central precocious puberty occurred before irradiation in four cases and after irradiation in 18. Eleven of the 17 patients with neurofibromatosis 1 had PP. Before irradiation, five of 21 patients lacked GH, zero of 21 lacked thyroid-stimulating hormone, and zero of 13 lacked adrenocorticotropin. After irradiation, 35 of 35 lacked GH, 28 of 35 lacked thyroid-stimulating hormone, and six of 35 lacked adrenocorticotropin; puberty was delayed in 15 patients. Adult height was -0.8 +/- 0.2 SD, below target height (0.2 +/- 0.2 SD, P <.0001), similar in patients with and without PP, but lower in those with neurofibromatosis 1 (-1.4 +/- 0.4 SD) than in those without (-0.3 +/- 0.3 SD, P =.04). CONCLUSIONS: Optic pathway tumors cause PP, but cranial irradiation causes most of the other hypothalamic-pituitary disorders. Adult height of patients given GH or gonadotropin hormone-releasing hormone analogue seems to depend on neurofibromatosis 1.
Subject(s)
Body Height , Cranial Irradiation/adverse effects , Growth Disorders/physiopathology , Optic Nerve Neoplasms/radiotherapy , Body Height/physiology , Body Height/radiation effects , Child , Female , Humans , Male , Neurofibromatosis 1/complications , Neurofibromatosis 1/physiopathology , Optic Nerve Neoplasms/physiopathology , Pituitary Irradiation/adverse effects , Puberty, Precocious/complications , Puberty, Precocious/physiopathology , Radiotherapy DosageABSTRACT
por ciento
Subject(s)
Humans , Child , Body Height/radiation effects , Drug Therapy/adverse effects , Growth , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Radiation EffectsABSTRACT
BACKGROUND: The treatment of the acute lymphocytic leukaemia can determine impaired growth. SUBJECTS AND METHOD: All the patients had length measurements at the time of the beginning of the treatment and, at least, one year after the end of it. CONCLUSIONS: There was impaired growth after the treatment according to the dose regimens (18 or 24 Grays). No relation was observed related to the age at the diagnosis.
Subject(s)
Cranial Irradiation/adverse effects , Growth/radiation effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Age Factors , Body Height/radiation effects , Child , Child, Preschool , Female , Humans , Infant , Retrospective StudiesABSTRACT
Objetivo. Determinar alteraçoes no crescimento após o tratamento de leucemia linfóide aguda em meninas. Pacientes e Métodos. Realizou-se estudo restrospectivo com 59 meninas que apresentavam medidas de estatura antes e com no mínimo um ano do tratamento, subdivididas de acordo com a dose de radioterapia cranial utilizada [18 ou 24 Grays Gy] e com a idade no início do tratamento (antes e após os cinco anos de idade). Resultados. Observou-se deficiência do crescimento com um, dois e mais de dois anos do tratamento. O crescimento foi mais afetado no grupo tratado com 24Gy, quando comparado com 18Gy. Nao houve diferenças com relaçao à idade no início do tratamento. Conclusoes. Houve retardo no crescimento após o tratamento, independentemente da idade em que foi realizado, mas dependente da dose de radioterapia cranial utilizada.
Subject(s)
Child , Child, Preschool , Infant , Female , Humans , Cranial Irradiation/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Growth/radiation effects , Body Height/radiation effects , Retrospective Studies , Age FactorsABSTRACT
Objetivos: Com o objetivo de avaliar o crescimento de meninas durante o tratamento da leucemia linfóide aguda na infância, realizou-se um estudo retrospectivo e descritivo no Centro Infantil de Investigaçöes Hematológicas "Dr. Domingos A. Boldrini (Campinas - SP)". Casuística e método: Foram selecionadas 75 meninas com idade média de 4,6 anos. O grupo foi subdividido de acordo com a dose de radioterapia cranial [18 a 24 Grays (Gy)] e com a idade no início do tratamento (menos de cinco anos e com cinco ou mais anos). A estatura foi avaliada no início e ao final do tratamento através do SDS (xx). DP Resultados: Nossos resultados mostraram que a média do SDS ao final foi inferior à do início do tratamento, sendo esta diferença mais importante no grupo com 24Gy. Conclusöes: Ao final do tratamento as meninas ficaram proporcionalmente mais baixas do que antes e que o comprometimento do crescimento foi mais acentuado no grupo tratado com 24Gy. Näo houve diferença entre o grupo tratado antes dos cinco anos e o tratado com cinco ou mais anos.
Subject(s)
Humans , Female , Child, Preschool , Child , Body Height/radiation effects , Growth/radiation effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Linear Models , Retrospective StudiesABSTRACT
We analyzed growth and final heights in 127 patients (68 female patients) treated for childhood acute lymphoblastic leukemia. Central nervous system prophylaxis included either no cranial radiation therapy (CRT) (n = 38), irradiation with 1800 centigrays (cGy) (n = 36), or irradiation with 2400 cGy (n = 53). None of the patients received spinal irradiation. Mean (+/- SEM) age at diagnosis was 6.4 +/- 0.25 years, mean height standard deviation score (SDS) at diagnosis was 0.28 +/- 0.12, and mean age at final height was 18.26 +/- 0.19 years. The change in height SDS between diagnosis and achievement of final height was significant for all treatment groups: -0.49 +/- 0.14, no CRT; -0.65 +/- 0.15, 1800 cGy; and -1.38 +/- 0.16, 2400 cGy. Irradiated patients had a greater loss in height SDS compared with the nonirradiated patients (p < 0.01), and those treated with 2400 cGy CRT had a greater decrease in final height SDS than the patients treated with 1800 cGy (p < 0.01). Both younger age and female sex were significantly associated with a greater decrease in height SDS in the patients treated with CRT; girls < or = 4 years of age at diagnosis had a mean loss in height SDS that was more than twice that observed for others treated with the same dose of CRT. Thus, although modern regimens for acute lymphoblastic leukemia (no CRT or 1800 cGy CRT) appear overall to have only a modest impact on final height, patients, especially girls, treated with 1800 cGy CRT at a young age remain at risk for clinically significant growth failure.