RESUMEN
Treatment of naive children with GH deficiency has relied upon long-term replacement therapy with daily injections of GH. The daily schedule may be inconvenient for patients and their caregivers, possibly promoting nonadherence with the treatment regimen or premature termination of treatment. We studied a new sustained release GH formulation, administered once or twice monthly, to determine its efficacy and safety in this population. Seventy-four prepubertal patients with documented GH deficiency were randomized to receive sustained release recombinant human GH at either 1.5 mg/kg once monthly or 0.75 mg/kg twice monthly by sc injection in a 6-month open-label study. Efficacy was determined by growth data from 69 patients completing 6 months and 56 patients completing 12 months in an extension study. Growth rates were significantly increased over baseline and were similar for the two dosage groups. The mean (+/-SD) annualized growth rate (pooled data) was 8.4 +/- 2.1 cm/yr at 6 months, and the growth rate was 7.8 +/- 1.8 at 12 months compared with 4.5 +/- 2.3 at baseline. Standardized height, bone age, and predicted adult height assessments demonstrated catch-up growth without excessive skeletal maturation. Injection site-related events (including pain, erythema, and nodules) were the most commonly reported adverse events; no serious adverse events related to treatment were reported. Laboratory studies documented no accumulation of trough GH or IGF-I levels during treatment, nor did glucose intolerance or persistent hyperinsulinism develop. Sustained release recombinant human GH is safe and effective for long-term GH replacement in children with GH deficiency. Patients achieved similar growth velocities when sustained release GH was given once or twice monthly. The enhanced convenience of this dosage form may result in greater long-term adherence to the treatment regimen.
Asunto(s)
Hormona del Crecimiento/administración & dosificación , Hormona de Crecimiento Humana/deficiencia , Anticuerpos/sangre , Niño , Preescolar , Femenino , Crecimiento/efectos de los fármacos , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/inmunología , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , MasculinoRESUMEN
Atopic dermatitis, common among infants and children, is an intensely pruritic, chronic, inflammatory dermatosis that is traditionally treated with emollients for dry skin and topical corticosteroids for inflamed areas. A multicenter, 3-week, open-label study evaluated prednicarbate emollient cream 0.1%, a nonhalogenated midpotency corticosteroid, in 55 patients aged 4 months to 12 years who were diagnosed with atopic dermatitis. No suppression of the hypothalamic-pituitary-adrenal (HPA) axis was evidenced by serum cortisol levels obtained before and after intravenous injection of 250 mg of cosyntropin on days 1 and 22, and biochemical tests detected no other systemic effects. Adverse events were few and within the expected range. Prednicarbate resulted in improvements based on global evaluations and sign/symptom scores. In conclusion, this study found prednicarbate emollient cream 0.1% to be safe and effective for the treatment of atopic dermatitis in pediatric patients for up to 3 weeks.
Asunto(s)
Antiinflamatorios/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Prednisolona/análogos & derivados , Prednisolona/administración & dosificación , Administración Tópica , Adolescente , Niño , Preescolar , Glucocorticoides , Humanos , Lactante , Pomadas/administración & dosificaciónRESUMEN
The murine Lbx2 gene is a member of the ladybird family of homeobox genes, which is expressed in the developing urogenital system, eye, and brain. Using transgenic mice, we demonstrate that 9 kb of the 5' flanking region of mouse Lbx2 is able to direct expression of a reporter gene in a tissue-specific manner recapitulating the endogenous expression pattern. This regulatory region provides a novel reagent allowing for transgenic expression in the developing urogenital ridge. In addition, we describe the identification of the human homologue, LBX2. Comparison of the human LBX2 and mouse Lbx2 sequences upstream of the coding regions reveals sequence conservation suggesting conserved regulatory regions. Both the human LBX2 and the mouse Lbx2 genes have similar genomic structures and are composed of two exons separated by an intron. We mapped the mouse Lbx2 gene to 35 cM on chromosome 6 and the human LBX2 gene to a homologous region of chromosome 2p13. This is a candidate region for several inherited disorders, including Alström syndrome, a disorder that includes ocular, urogenital, and renal abnormalities. Given the expression pattern of Lbx2, the chromosomal location in humans, and the potential function of mammalian ladybird genes, we have begun to analyze patients with ocular disorders and those with Alström syndrome for mutations in LBX2. Although polymorphisms were identified, our results indicate that mutations in the coding region of LBX2 do not account for Alström syndrome in the six kindreds analyzed.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de Homeodominio/genética , Hipogonadismo/genética , Enfermedades Renales/genética , Mutación , Obesidad/genética , Regiones Promotoras Genéticas , Enfermedades de la Retina/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , Análisis Mutacional de ADN , Ojo/embriología , Oftalmopatías/genética , Salud de la Familia , Femenino , Genes Recesivos , Genes Reporteros , Pruebas Genéticas , Humanos , Hibridación in Situ , Intrones , Masculino , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Linaje , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Síndrome , Distribución TisularRESUMEN
Five patients with well-controlled, long-standing, central diabetes insipidus had acute development of dehydration, hyponatremia, and inappropriate natriuresis in the setting of polyuria resistant to exogenous antidiuretic hormone. Hyponatremia and dehydration worsened with fluid restriction or use of exogenous antidiuretic hormone. We discuss the challenges in diagnosis and management of probable salt wasting in children with central diabetes insipidus.
Asunto(s)
Diabetes Insípida Neurogénica/diagnóstico , Diabetes Insípida Neurogénica/terapia , Adolescente , Adulto , Niño , Preescolar , Diabetes Insípida Neurogénica/complicaciones , Femenino , Humanos , Hiponatremia/etiología , Masculino , Poliuria/etiología , Cloruro de Sodio/uso terapéutico , Vasopresinas/efectos adversos , Vasopresinas/uso terapéuticoRESUMEN
PURPOSE: Progress has been made in the treatment of medulloblastoma, the most common childhood malignant brain tumor: However, many long-term survivors will have posttherapy growth hormone insufficiency with resultant linear growth retardation. Growth hormone replacement therapy (GHRT) may significantly improve growth, but there is often reluctance to initiate GHRT because of concerns of an increased likelihood of tumor relapse. PATIENTS AND METHODS: This study retrospectively reviewed the use of GHRT for survivors of medulloblastoma in 11 neuro-oncology centers in North America who received initial treatment for disease between 1980 and 1993 to determine its impact on disease control. A Landmark analysis was used to evaluate the relative risk of relapse in surviving patients. RESULTS: Five hundred forty-five consecutive patients less than 15 years of age at diagnosis were identified. Six-year progression-free survival (mean +/- SD) was 40% +/- 5% in children less than 3 years of age at diagnosis compared with 59% +/- 3% for older patients. Older patients with total or near-total resections (P = .003) and localized disease at diagnosis (P < .0001) had the highest likelihood of survival. One hundred seventy patients (33% +/- 3% of the cohort) received GHRT. GHRT use varied widely among institutions, ranging from 5% to 73%. GHRT was begun a mean of 3.9 years after diagnosis, later in children younger than 3 years at diagnosis (5.4 years). By Landmark analyses, for those surviving 2, 3, and 5 years after diagnosis, there was no evidence that GHRT increased the rate of disease relapse. CONCLUSION: This large retrospective review demonstrates that GHRT is underutilized in survivors of medulloblastoma and is used relatively late in the course of the illness. GHRT is not associated with an increased likelihood of disease relapse.
Asunto(s)
Neoplasias Cerebelosas/complicaciones , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/etiología , Hormona de Crecimiento Humana/uso terapéutico , Meduloblastoma/complicaciones , Adolescente , Neoplasias Cerebelosas/terapia , Niño , Preescolar , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/deficiencia , Humanos , Meduloblastoma/terapia , Recurrencia Local de Neoplasia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Our study was designed to characterize the patterns of growth, in the medium term, of children with functionally univentricular hearts managed with a hemi-Fontan procedure in infancy, followed by a modified Fontan operation in early childhood. Failure of growth is common in patients with congenital cardiac malformations, and may be related to congestive heart failure and hypoxia. Repair of simple lesions appears to reverse the retardation in growth. Palliation of the functionally single ventricular physiology with a staged Fontan operation reduces the adverse effects of hypoxemia and prolonged ventricular volume overload. The impact of this approach on somatic growth is unknown. Retrospectively, we reviewed the parameters of growth of all children with functionally univentricular hearts followed primarily at our institution who had completed a staged construction of the Fontan circulation between January 1990 and December 1995. Measurements were available on all children prior to surgery, and annually for three years following the Fontan operation. Data was obtained on siblings and parents for comparative purposes. The criterions of eligibility for inclusion were satisfied by 65 patients. The mean Z score for weight was -1.5 +/- 1.2 at the time of the hemi-Fontan operation. Weight improved by the time of completion of the Fontan circulation (-0.91 +/- 0.99), and for the first two years following the Fontan operation, but never normalized. The mean Z scores for height at the hemi-Fontan and Fontan operations were -0.67 +/- 1.1 and -0.89 +/- 1.2 respectively. At most recent follow-up, with a mean age of 6.1 +/- 1.3 years, and a mean time from the Fontan operation of 4.4 +/- 1.4 years, the mean Z score for height was -1.15 +/- 1.2, and was significantly less than comparable Z scores for parents and siblings. In our experience, children with functionally univentricular hearts who have been palliated with a Fontan operation are significantly underweight and shorter than the general population and their siblings.
Asunto(s)
Procedimiento de Fontan/efectos adversos , Procedimiento de Fontan/métodos , Trastornos del Crecimiento/etiología , Cardiopatías Congénitas/cirugía , Factores de Edad , Estatura/fisiología , Peso Corporal/fisiología , Distribución de Chi-Cuadrado , Desarrollo Infantil , Preescolar , Femenino , Estudios de Seguimiento , Procedimiento de Fontan/mortalidad , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/epidemiología , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/mortalidad , Humanos , Lactante , Masculino , Reoperación , Estudios Retrospectivos , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: The growth hormone (GH)-dependent growth factors insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be superior to provocative GH testing in diagnosing GH deficiency (GHD) in children. In adults with brain tumours (BT) and GHD, however, provocative GH testing more accurately reflects GHD than either IGF-I or IGFBP-3. We assessed growth factor levels in children with GHD due to BT with respect to brain tumour type, pubertal stage, growth velocity, bone age delay, and body mass index (BMI). DESIGN: Retrospective case review of all patients followed at our centre with GHD following treatment of BT. PATIENTS: 72 children (51 M, 21 F) with BT diagnosed with GHD by clinical and auxological criteria, including provocative GH testing, in whom pre-GH treatment IGF-I and IGFBP-3 levels were obtained. MEASUREMENTS: Auxological data, including height, weight, growth velocity, and pubertal stage; and biochemical data, including GH response to provocative GH testing and pre-GH treatment serum IGF-I and IGFBP-3 concentrations. RESULTS: IGF-I levels were normal (above -2 SD) in 19 of 70 children (27%), and IGFBP-3 levels were normal in 21 of 42 (50%). In children with GHD, pubertal stage correlated significantly with both IGF-I (r = 0.328, p < 0.006) and IGFBP-3 (r = 0.364, P < 0.02). Normal IGF-1 levels were found in 1/15 children with craniopharyngioma (Cranio) (7%), 10/30 with primitive neuroectodermal tumours (PNET) (33%), and 5/12 children with hypothalamic/chiasmatic glioma (HCG) (42%) (P < 0. 05). IGFBP-3 levels were normal in 4/13 Cranio patients (31%), 8/15 PNET patients (53%), and 6/8 HCG patients (75%) (P = ns). Tanner staging varied significantly among tumour types: mode = 1 for Cranio and PNET vs. mode = 3 for HCG (P < 0.03). BMI did not differ between patients with low vs. normal growth factor levels. CONCLUSIONS: Low IGF-I levels were more predictive of growth hormone deficiency than low IGFBP-3 levels in our brain tumour patients, but both were poor predictors of growth hormone deficiency in children with hypothalamic-chiasmatic glioma and in pubertal children. Serum IGF-I and IGFBP-3 levels, therefore, do not always reflect growth hormone deficiency in children with brain tumours, particularly in those with hypothalamic-chiasmatic glioma or those already in puberty.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Hormona del Crecimiento/deficiencia , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Tumores Neuroectodérmicos Primitivos/metabolismo , Análisis de Varianza , Biomarcadores/sangre , Niño , Craneofaringioma/metabolismo , Femenino , Glioma/metabolismo , Humanos , Neoplasias Hipotalámicas/metabolismo , Masculino , Neoplasias Hipofisarias/metabolismo , Pubertad/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: As more pediatric patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) survive, comparison of the late effects of various therapies becomes increasingly important. This study of survivors of AML is the largest to date comparing the late effects of patients treated with chemotherapy (CT) with or without irradiation (RT) or CT followed by bone marrow transplantation (BMT). PROCEDURE: In a retrospective review of 228 patients with AML or MDS from 1970 to 1995, 62 survived and had follow-up data available more than 1 year following completion of therapy. Ten patients with Down syndrome were excluded. Twenty-six received CT and 26 underwent BMT. Weight and height Z scores, endocrine, ophthalmologic, renal, and cardiac function following CT +/- RT or BMT +/- total body irradiation (TBI) were compared at a mean follow-up of 7.4 and 5.6 years, respectively. RESULTS: Both groups experienced a decrement in height and increase in weight. The mean height Z score in the CT group fell from -0.29 to -0.72 (P = 0.02) and mean weight Z score rose from -0.06 at diagnosis (T0) to 0.51 at last follow-up (T2) (P = 0.02), a finding no longer significant when patients who received RT were excluded. The mean height Z score in the BMT group fell from -0.17 at TO to -0.65 at T2 (P = 0.02), while the mean weight rose from 0.29 at T0 to 0.84 at T2, (P = 0.07). Six of 9 BMT adolescent girls experienced ovarian failure versus 0 of 11 girls treated with CT (P = 0.002). Seven adolescent CT males and seven BMT males showed normal pubertal progression. Two BMT patients require thyroid hormone supplementation, and one receives growth hormone. Six BMT patients and one CT patient developed cataracts, all of whom received irradiation (P = 0.10). Serum creatinine level, hypertension, or left ventricular shortening fraction were not different in the two groups. One BMT patient has chronic graft versus host disease. CONCLUSIONS: Growth, renal, and cardiac functions were similar in the two groups. The need for estrogen supplementation was more frequent following BMT. Recommendations concerning therapy for AML should depend on the probability of cure.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/terapia , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/terapia , Enfermedad Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Catarata/etiología , Niño , Preescolar , Enfermedad Crónica , Terapia Combinada , Irradiación Craneana/efectos adversos , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Corazón/efectos de los fármacos , Corazón/fisiopatología , Humanos , Riñón/efectos de los fármacos , Riñón/fisiopatología , Leucemia Mieloide/radioterapia , Masculino , Síndromes Mielodisplásicos/radioterapia , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Trastornos del Crecimiento/terapia , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/deficiencia , Neoplasias/mortalidad , Neoplasias Encefálicas/etiología , Niño , Hormona del Crecimiento/uso terapéutico , Humanos , Recurrencia Local de Neoplasia/etiología , Neoplasias Primarias Secundarias/etiología , SobrevivientesRESUMEN
Estrogen has a biphasic effect on growth, stimulatory at low doses but inhibitory at higher doses. Therefore, designing optimal sex hormone replacement treatment in girls with Turner syndrome (TS) who are being treated with growth hormone (GH) involves considering the dose and form of the estrogen as well as the route and timing of its administration. We report here a preliminary analysis of a study to test the concept that an optimal estrogen replacement regimen should consist of estradiol administered in a low dose by a systemic route. The study population consisted of 9 girls with TS who had been treated with GH for 6 or more months. When the girls were 12 to 15 years old, we added depot estradiol at a monthly intramuscular dose of 0.2 mg and increased the dose at 6-month intervals to 0.4, 0.6, and, in 7 of the girls, 0.8 mg. We compared the results in these subjects with those in a matched group of 37 patients with TS in whom routine estrogen treatment had been started at similar ages and who were treated with a similar course of GH therapy. The gain in height at 2 years was 2.6 cm greater in those who were treated with depot estradiol than in those who were treated with routine estrogen. The bone age in the patients who were treated with depot estradiol increased in proportion to their chronologic age, suggesting that this difference indicates an increase in their predicted adult height. We conclude that using very low doses of systemic estradiol to induce puberty before the age of 15 years in girls with TS who are treated with GH, instead of using routine estrogen therapy, can result in increased final heights.
Asunto(s)
Terapia de Reemplazo de Estrógeno , Trastornos del Crecimiento/terapia , Síndrome de Turner/terapia , Adolescente , Estatura , Niño , Preparaciones de Acción Retardada , Estradiol/administración & dosificación , Terapia de Reemplazo de Estrógeno/métodos , Femenino , Trastornos del Crecimiento/complicaciones , Hormona del Crecimiento/uso terapéutico , Humanos , Síndrome de Turner/complicaciones , Síndrome de Turner/fisiopatologíaRESUMEN
Optic nerve hypoplasia is a congenital disc anomaly associated with growth hormone deficiency (GHD). Pseudotumor cerebri is an adverse event associated with growth hormone treatment (hGH) and manifested by increased intracranial pressure and papilledema. Pseudopapilledema is a generic ophthalmologic term encompassing several conditions, including congenital disc anomalies. It is benign and can be distinguished from papilledema by physical examination. The objective of this report is to document that congenital disc abnormalities, which can be confused with papilledema, occur in children with GHD. Three patients with GHD had fundoscopic examinations suggestive of papilledema and possibly pseudotumor cerebri. The abnormal optic nerves were characteristic of pseudo-papilledema, and appear to be a variant of optic nerve hypoplasia. The finding of optic disc abnormality during hGH may reflect pseudo-papilledema and not pseudotumor cerebri. Of equal importance, the reported patients indicate that the finding of pseudopapilledema in short children should suggest the possibility of GHD.
Asunto(s)
Trastornos del Crecimiento/complicaciones , Hormona de Crecimiento Humana/deficiencia , Disco Óptico/anomalías , Papiledema/diagnóstico , Niño , Diagnóstico Diferencial , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Masculino , Papiledema/complicaciones , Seudotumor Cerebral/complicaciones , Seudotumor Cerebral/diagnósticoRESUMEN
The list of findings associated with the 22q11.2 deletion is quite long and varies from patient to patient. The hallmark features include: conoruncal cardiac anomalies, palatal defects, thymic aplasia or hypoplasia, T cell abnormalities, mild facial dysmorphia, and learning disabilities. The 22q11.2 deletion has been seen in association with the DiGeorge sequence, velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome, isolated conotruncal cardiac anomalies, and some cases of autosomal dominant Optiz G/BBB syndrome. Short stature has been seen in one to two thirds of children reported in the literature with a diagnosis of VCFS, but growth hormone deficiency (GHD) has not been described in conjunction with this diagnosis. We present 4 patients with a 22q11.2 deletion and short stature who were found to have abnormalities in the growth hormone-insulin-like growth factor I axis. All had growth factors less than -2 SD for age and failed provocative growth hormone testing. Two patients were found to have abnormal pituitary anatomy. In our population, the incidence of GHD in 4 or 95 children with 22q11 deletion is significantly greater than the estimated incidence of GHD in the general population. Children with a 22q11.2 deletion appear to be at a greater risk for pituitary abnormalities. Therefore, those children with the 22q11.2 deletion and short stature or poor growth should be evaluated for GHD, as replacement growth hormone therapy may improve their growth velocity and final height prediction.
Asunto(s)
Cromosomas Humanos Par 22 , Eliminación de Gen , Trastornos del Crecimiento/genética , Hormona de Crecimiento Humana/deficiencia , Niño , Preescolar , Femenino , Humanos , Masculino , FenotipoRESUMEN
OBJECTIVE: We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy. DESIGN: Descriptive retrospective study using case note review analysis. PATIENTS: The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow-up was 3.6 years. Thirty-eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment. MEASUREMENTS: Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic-pituitary function. RESULTS: Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). HOwever, 15 children treated with more than 15 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery. CONCLUSIONS: Nearly all studies assessing the patients with different tumour therapy evaluate patients wit different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different form of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.
Asunto(s)
Neoplasias de los Nervios Craneales/metabolismo , Glioma/metabolismo , Hormona del Crecimiento/deficiencia , Neoplasias Hipotalámicas/metabolismo , Quiasma Óptico , Adolescente , Corticoesteroides/deficiencia , Adulto , Niño , Irradiación Craneana/efectos adversos , Neoplasias de los Nervios Craneales/radioterapia , Neoplasias de los Nervios Craneales/cirugía , Diabetes Insípida/etiología , Femenino , Estudios de Seguimiento , Glioma/radioterapia , Glioma/cirugía , Humanos , Hipogonadismo/etiología , Neoplasias Hipotalámicas/radioterapia , Neoplasias Hipotalámicas/cirugía , Hipotiroidismo/etiología , Masculino , Neurofibromatosis/metabolismo , Pubertad Precoz/etiología , Estudios Retrospectivos , SobrevivientesRESUMEN
Congenital adrenal hyperplasia results from an adrenal enzyme deficiency, that causes an underproduction of glucocorticoids and sometimes mineralocorticoids and a resultant overproduction of androgens, until treatment with replacement glucocorticoids is instituted. The goal of this study was to determine the frequency and etiology of white-matter changes and temporal lobe atrophy demonstrable on magnetic resonance imaging (MRI) in a group of children and young adults with congenital adrenal hyperplasia. About one third of the patients evidenced white-matter abnormalities or temporal lobe atrophy. All patients, except one with a known stroke, had normal neurologic examinations. Exposure to excess exogenous glucocorticoids in the process of being treated for congenital adrenal hyperplasia is the most theoretically appealing explanation for these MRI findings. However, the relationship of MRI findings to treatment status (over-versus under-suppressed) does not run in clear parallel.
Asunto(s)
Hiperplasia Suprarrenal Congénita/diagnóstico , Encéfalo/patología , Lóbulo Temporal/patología , Adolescente , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Hiperplasia Suprarrenal Congénita/patología , Adulto , Atrofia , Niño , Preescolar , Femenino , Glucocorticoides/uso terapéutico , Humanos , Lactante , Imagen por Resonancia Magnética , MasculinoRESUMEN
A submicroscopic deletion of chromosome 22q11.2 has been identified in the majority of patients with the DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. We have evaluated 181 patients with this deletion. We describe our cohort of patients, how they presented, and what has been learned by having the same subspecialists evaluate all of the children. The results help define the extremely variable phenotype associated with this submicroscopic deletion and will assist clinicians in formulating a management plan based on these findings.
Asunto(s)
Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 22/genética , Adolescente , Adulto , Niño , Preescolar , Fisura del Paladar/genética , Estudios de Cohortes , Síndrome de DiGeorge/genética , Cara/anomalías , Femenino , Pruebas Genéticas , Cardiopatías Congénitas/genética , Humanos , Lactante , Masculino , Fenotipo , SíndromeRESUMEN
Two hundred fifty children being treated with growth hormone were screened for scoliosis by using the Adams and Bunnell techniques. If indicated, an anteroposterior radiograph was done and measured by the Cobb and Risser methods. Scoliosis was defined as a frontal curve of > or = 10 degrees; progression, as a sustained increase of > or = 5 degrees, and a progressive curve as one > or = 25 degrees and meeting our criteria for orthotic management. In 10 of the 250 patients, scoliosis developed. Six curves were double major thoracic and lumbar; three thoraco-lumbar; and one single thoracic. Six of the 10 patients had progressive curves and required an orthosis. Their average annualized rate of progression was 26 degrees. Progression was associated with double major curves and an earlier Risser stage. Despite bracing, progression continued to fusion in three patients. We conclude that growth hormone may increase the risk of progression of scoliosis. Furthermore, the progression is frequently rapid and requires special vigilance by the treating physician.
Asunto(s)
Hormona de Crecimiento Humana/efectos adversos , Escoliosis/inducido químicamente , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Masculino , Escoliosis/diagnósticoRESUMEN
PURPOSE: The purpose of this study was to evaluate the effect of busulfan and cyclophosphamide (BUCY) as conditioning regimen for bone marrow transplantation (BMT) on growth of children following BMT. PATIENTS AND METHODS: Growth assessment was prospectively done in all 25 children who underwent BMT following BUCY conditioning from 1989 to 1994 at Children's Hospital of Philadelphia. The height and growth rates were expressed as standard deviation scores (SDS). The height SDS prior to BMT were compared with 1, 2, and 3 years post-BMT. The growth rate SDS 1 year and 2 years post-BMT were also compared. Pubertal children were excluded from the analysis of growth rate. Median age of patients was 7 years (range, 1.3-15 years). A total of 22/25 patients were transplanted for AML, and three patients had myelodysplastic syndrome. Equal numbers of patients had autologous and allogeneic transplants. Seven patients received corticosteroids for varying lengths of time. The pre-BMT height SDS (mean +/- SD) for the group was -0.4 +/- 1.3. The mean height SDS for 19 children at 1 year post-BMT was +/- 0.1 +/- 1.2 and for 10 children, 2 years post-BMT was -0.3 +/- 1.6. Seven children who were 3 years post-BMT had the mean height SDS of -0.2 +/- 1.5. There was no statistically significant difference between pre-BMT height SDS and 1 year post-BMT (p = 0.49) and 2 years post-BMT (p = 0.42). The mean growth rate at 1 year post-BMT was -0.1 +/- 2.7 and at 2 years post-BMT was -0.9 +/- 2.3. The difference was not statistically different (p = 0.15). Somatomedin-C (insulin growth factor 1, IGF-1) levels were normal in all 13 children tested at 1 year post-BMT. IGF binding protein (BP)-3 levels were done in 10 children at 1 year and were found to be normal in all. Thyroid function studies were done in all patients pre-BMT and 1 year post-BMT and were normal for all. Bone age assessment was appropriate for age in all 14 patients tested at 1 year post-BMT. CONCLUSIONS: There was no evidence of growth failure following BMT with BUCY conditioning in this group of patients.
Asunto(s)
Trasplante de Médula Ósea/métodos , Busulfano/efectos adversos , Ciclofosfamida/efectos adversos , Crecimiento/efectos de los fármacos , Adolescente , Desarrollo Óseo/efectos de los fármacos , Niño , Preescolar , Femenino , Humanos , Lactante , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Glándula Tiroides/fisiologíaRESUMEN
The effects of cancer therapy on growth are reviewed. The effects of radiation and chemotherapy on growth hormone production and growth hormone responsiveness by peripheral tissues are examined. The effects of radiotherapy and chemotherapy on other endocrine function pertaining to growth also are discussed. An approach to surveillance of pediatric cancer survivors pertaining to growth and development is suggested.
Asunto(s)
Crecimiento/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Antineoplásicos/efectos adversos , Niño , Enfermedades del Sistema Endocrino/etiología , Crecimiento/efectos de la radiación , Trastornos del Crecimiento/inducido químicamente , HumanosRESUMEN
As of October 1993 the National Cooperative Growth Study included 1262 children with brain tumor who were treated with growth hormone. The type of brain tumor was specified in 947 (75%) of these children. The most common types were glioma, medulloblastoma, and craniopharyngioma, accounting for 91.3% of all those for which type was specified. Brain tumor recurred in 83 (6.6%) of the 1262 children over a total of 6115 patient-years at risk. The frequencies of tumor recurrence in children with low-grade glioma (18.1%), medulloblastoma (7.2%), and craniopharyngioma (6.4%) are lower than those in published reports of tumor recurrence in the general pediatric population with the same types of tumors. The analysis cannot conclusively show that no increased risk of tumor recurrence exists, however, because of the potential incompleteness of data reporting in the National Cooperative Growth Study. Nevertheless the findings are reassuring that children with the more common types of brain tumor who are treated with growth hormone do not seem to be at excessive risk for tumor recurrence.
Asunto(s)
Neoplasias Encefálicas/epidemiología , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/uso terapéutico , Recurrencia Local de Neoplasia/epidemiología , Sistemas de Registro de Reacción Adversa a Medicamentos , Neoplasias Encefálicas/diagnóstico , Niño , Preescolar , Bases de Datos Factuales , Trastornos del Crecimiento/etiología , Humanos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
The National Cooperative Growth Study has monitored the safety of recombinant human GH (rhGH) since 1985. Data have been collected from more than 19,000 children representing over 47,000 patient-years of rhGH treatment. Children receiving GH for renal disease were more likely to develop problems such as intracranial hypertension than those with GH deficiency (P < 0.01). Children with idiopathic short stature were less likely to develop slipped capital femoral epiphysis than those with GH deficiency or Turner's syndrome (P < 0.01). There was no evidence of an increased recurrence of leukemia or central nervous system tumors. There were 3 new cases of leukemia in children without known risk factors for developing leukemia and 5 cases in children with known risk factors. Growth deceleration associated with high affinity, high capacity antibodies to GH was found in only 2 of 5039 subjects tested (0.04%). Major adverse events in association with rhGH treatment have been rare, and preexisting medical conditions such as renal insufficiency may affect their frequency.