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      Seqüelas endócrinas da radioterapia no tratamento do câncer na infância e adolescência Translated title: Endocrine sequelae after radiotherapy in childhood and adolescence

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          Abstract

          A radioterapia resulta em endocrinopatias, osteoporose, obesidade e seqüelas neurológicas em pacientes tratados por câncer. A deficiência de GH é a complicação mais freqüente no eixo hipotálamo-hipofisário. A freqüência, prazo de surgimento e gravidade da deficiência de GH dependem da dose recebida durante a irradiação craniana, mas idade à radioterapia e fracionamento da dose também são variáveis importantes. Outras anormalidades do eixo hipotálamo-hipofisário são igualmente dose-dependentes. Baixas doses de irradiação induzem puberdade precoce ou avançada, enquanto altas doses provocam deficiência gonadotrópica. Complicações endócrinas secundárias à irradiação periférica, como distúrbios gonadais ou tireoidianos são descritos. Mesmo com secreção normal de GH, o crescimento pode ser comprometido por lesões ósseas após irradiação corporal total ou crânio-espinhal. Resultados melhores sobre a estatura final têm sido obtidos com reposição de GH em associação com o tratamento da puberdade precoce ou avançada. O objetivo desta revisão é a abordagem das seqüelas endócrinas tardias da radioterapia.

          Translated abstract

          Radiotherapy may result in endocrine abnormalities, osteoporosis, obesity and neurological sequelae in patients treated for cancer. In the hypothalamo-pituitary area, GH deficiency is the most frequent complication. The frequency, delay of appearance and severity of GH deficiency depend most on the dose delivered during cranial irradiation but variables as age at treatment and fractionation schedule may play an important role as well. Other hypothalamo-pituitary dysfunctions are also dose-dependent. Low dose cranial irradiation may induce precocious or early puberty, while high doses are related to gonadotropin deficiency. Endocrine complications due to extracranial irradiaton such as gonadal or thyroid abnormalities are described. In spite of normal GH secretion, linear growth may be impaired by bone lesions secondary to craniospinal or total body irradiation. Results on final height have been optimized by better indicators of GH therapy associated with adequate treatment of early or precocious puberty. The purpose of this review is to explore the late endocrine sequelae of radiotherapy.

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          Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study.

          The objectives of this study were 1) to compare final height and body mass index (BMI) between adult survivors of childhood brain cancer and age- and sex-matched population norms, 2) to quantify the effects of treatment- and cancer-related factors on the risk of final height below the 10th percentile (adult short stature) or having a BMI of 30 kg/m(2) or more (obesity). Treatment records were abstracted and surveys completed by 921 adults aged 20-45 yr who were treated for brain cancer as children and were participants in the multicenter Childhood Cancer Survivor Study. Nearly 40% of childhood brain cancer survivors were below the 10th percentile for height. The strongest risk factors for adult short stature were young age at diagnosis and radiation treatment involving the hypothalamic-pituitary axis (HPA). The multivariate odds ratio for adult short stature among those 4 yr of age or younger at diagnosis, relative to ages 10-20 yr, was 5.67 (95% confidence interval, 3.6-8.9). HPA radiation exposure increased the risk of adult short stature in a dose-response fashion (trend test, P < 0.0001). Adjuvant chemotherapy was not an independent risk factor for adult short stature. BMI distribution in survivors did not differ appreciably from that of population norms; however, in females, young age at diagnosis and HPA radiation dose (trend test, P < 0.001) were associated with risk of obesity. Except for patients treated with surgery only, survivors of childhood brain cancer are at very high risk for adult short stature, and this risk increases with radiation dose involving the HPA. We did not find a corresponding elevated risk for obesity.
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            Vulnerability of the human Leydig cell to radiation damage is dependent upon age

            Testicular function was studied in three groups of patients previously treated for malignant disease, and a control group of adult males. The adult patients in groups one and two underwent unilateral orchidectomy for a testicular tumour but only in group two was this followed by post-operative high-dose irradiation (30 Gy) to the remaining testis. Four of the five boys in group three had a unilateral orchidectomy between the ages of 1 and 4 years and all five received a similar dose of irradiation (27·5–30 Gy) to the scrotum as in group two. The five subjects in group three were studied between the ages of 12 and 34 years. In group one the median basal testosterone level (16·0 nmol/l) was normal and the basal gonadotrophin levels mildly but significantly increased, reflecting a resetting of the pituitary-testicular axis following unilateral orchidectomy. In group two the median basal testosterone level (12·5 nmol/l) was significantly lower and the median basal FSH and LH levels were significantly higher than the respective values in group one, indicating that irradiation to the testis in adult life may damage both the germinal epithelium and the Leydig cells. All five males in group three showed grossly increased FSH and LH levels, with a median basal testosterone level (< 2·5 nmol/l) significantly lower than groups one and two. None of the five showed a testosterone response to a stimulation test with human chorionic gonadotrophin or underwent puberty spontaneously. The severe reduction in testosterone levels in group three compared with group two, despite the similarity of radiation dose received, suggests a much greater vulnerability to radiation-induced Leydig cell damage in the prepubertal boy compared with the adult male. Journal of Endocrinology (1989) 120, 161–165
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              Osteoporosis after cranial irradiation for acute lymphoblastic leukemia.

              A prospective study was conducted to investigate the possibility of osteoporosis after treatment for childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL had the trabecular bone density of the spine evaluated by quantitative computed tomography, 6 to 98 months (mean 42 months) after completion of chemotherapy. The ALL survivors had significantly lower bone density than age-, gender-, and race-matched nonleukemic control subjects had (10% less, p less than 0.001); this decrease was accounted for solely by the subset of patients who had received cranial irradiation (n = 30; p less than 0.001). The relative reduction in bone density in ALL survivors was unrelated to age at the time of diagnosis or time without therapy. The effects on bone density of 18 Gy and of 22.5 to 25.2 Gy were indistinguishable. We conclude that survivors of ALL commonly have reduced bone density in the lumbar spine and suggest that the diminution is related to nervous system irradiation, not to the disease or to chemotherapy.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                abem
                Arquivos Brasileiros de Endocrinologia & Metabologia
                Arq Bras Endocrinol Metab
                Sociedade Brasileira de Endocrinologia e Metabologia (São Paulo )
                1677-9487
                October 2005
                : 49
                : 5
                : 825-832
                Affiliations
                [1 ] Universidade Federal da Bahia Brazil
                [2 ] Université Paris Descartes France
                Article
                S0004-27302005000500025
                10.1590/S0004-27302005000500025
                37d17ebd-a76d-47f3-b387-c205c42bf1ad

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0004-2730&lng=en
                Categories
                ENDOCRINOLOGY & METABOLISM

                Endocrinology & Diabetes
                Radiotherapy,Children,Growth,Endocrine sequelae,Radioterapia,Crianças,Crescimento,Seqüelas endócrinas

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