RESUMO
BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH)-deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. Although recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy. OBJECTIVES AND METHODS: Effects of 24 months of GH treatment (1 mg/m(2)/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure, and fat utilization were assessed in 35 children with PWS. Percent body fat, lean muscle mass, and bone mineral density were measured by dual-energy x-ray absorptiometry. Indirect calorimetry was used to determine resting energy expenditure and to calculate the respiratory quotient. RESULTS: Compared with baseline evaluations, increased height velocity (SD score -1.1 +/- 2.5 to 2.2 +/- 2.3; P <. 001), reduced percent body fat (46.4% +/- 8.4% to 40.3% +/- 10.0%, P <.001), and improved respiratory muscle function and physical strength and agility (sit-ups, weight-lifts, running speed, and broad jump; P <.01) were observed after 24 months of GH treatment. A decline in respiratory quotient (0.81 +/- 0.07 to 0.75 +/- 0.06; P <. 01) and a trend toward increased resting energy expenditure were also observed. Changes in response to GH occurred predominantly during the initial 12 months of GH therapy. CONCLUSIONS: Children with PWS had sustained increases in lean body mass, decreases in percent body fat, improvements in physical strength and agility, and increased fat oxidation after 24 months of GH therapy. However, between 12 and 24 months, the growth rate slowed. Consequently, encouraging initial results require even more prolonged study to draw conclusions regarding the long-term value of GH therapy in changing body composition in children with PWS.
Assuntos
Composição Corporal , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Prader-Willi/fisiopatologia , Tecido Adiposo/metabolismo , Antropometria , Densidade Óssea , Criança , Metabolismo Energético , Seguimentos , Humanos , Aptidão Física , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition and diminished energy expenditure resembling a growth hormone deficient state. Hypothalamic dysfunction in PWS often includes decreased growth hormone (GH) secretion, suggesting a possible therapeutic role for exogenous GH treatment. OBJECTIVES AND METHODS: After 6 months of observation to determine baseline growth rate, and with the use of a 12-month randomized controlled study design, the effects of GH treatment (1 mg/m2/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 54 children with PWS (n = 35 treatment and n = 19 control). Percent body fat and bone mineral density were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotients. RESULTS: Stimulated levels of GH in response to clonidine testing were low in all patients (peak, 2.0 ng/mL). After 12 months, GH-treated subjects showed significantly increased height velocity Z scores (mean, 1.0 1.7 to 4.6 2.9; P <.001), decreased percent body fat (mean, 46.3% 8.4% to 38.3% 10.7%; P <.001), and improved respiratory muscle function, physical strength, and agility (sit-ups, weight-lifts, running speed, and coordination). A significant decline in respiratory quotients occurred during GH therapy (0.81 to 0.77, P <.001), but total REE did not change. CONCLUSIONS: GH treatment of children with PWS accelerated growth, decreased percent body fat, and increased fat oxidation but did not significantly increase total REE. Improvements in respiratory muscle strength, physical strength, and agility also occurred, suggesting that GH treatment may have value in reducing some physical disabilities experienced by children with PWS.
Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Prader-Willi/fisiopatologia , Tecido Adiposo/metabolismo , Composição Corporal , Densidade Óssea , Metabolismo dos Carboidratos , Criança , Metabolismo Energético , Feminino , Crescimento , Hormônio do Crescimento Humano/fisiologia , Humanos , Metabolismo dos Lipídeos , Masculino , Destreza Motora , Consumo de Oxigênio , RespiraçãoRESUMO
OBJECTIVE: To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma. STUDY DESIGN: In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year. Growth was evaluated monthly, whereas other safety variables and pulmonary function were evaluated periodically. RESULTS: The prepubescent patients showed no statistically significant differences in mean height, mean growth velocity, or mean skeletal age between any of the treatment groups at any time. Over a period of 1 year, mean height (+/- SE) increased 6.15 +/- 0.17 cm in the placebo group, 5.94 +/- 0.16 cm in the fluticasone propionate 50 microg group, and 5.73 +/- 0.13 cm in the fluticasone propionate 100 microg group (p = 0.308, overall). CONCLUSIONS: Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age.
Assuntos
Androstadienos/administração & dosagem , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Glucocorticoides/uso terapêutico , Crescimento/efeitos dos fármacos , Administração por Inalação , Androstadienos/efeitos adversos , Antiasmáticos/efeitos adversos , Antiasmáticos/farmacologia , Asma/fisiopatologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fluticasona , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Humanos , MasculinoRESUMO
BACKGROUND: Data have suggested that any increased incidence of leukemia in growth-hormone (GH)-treated patients was limited to those with known risk factors for leukemia. However, previous studies may have overestimated the numbers of patient-years of risk by not excluding data from "positive-risk-factor" patients. This risk was reanalyzed by using data on children in the National Cooperative Growth Study (NCGS), with correction for this possible confounding factor. METHODS: The risk of leukemia in GH-treated patients without known risk factors was determined by using patient-years of GH therapy and patient-years since first exposure to GH therapy and the values obtained were compared with values from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. RESULTS: Three cases of leukemia in patients without known risk factors were found in the NCGS database; 3.42 cases would be expected in the 119,846 patient-years in the analysis using time since GH exposure. Two of these cases of leukemia occurred during GH therapy (67,773 patient-years); 2.13 cases would be expected. CONCLUSION: Excluding data on patients with known risk factors for leukemia provides a more accurate estimate of the risks in GH-treated patients. The incidence of leukemia in these patients is comparable to that in the general population of age-matched children.
Assuntos
Hormônio do Crescimento Humano/efeitos adversos , Leucemia/induzido quimicamente , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Incidência , Sistemas de Informação , Masculino , National Institutes of Health (U.S.) , Fatores de Risco , Programa de SEER , Fatores de Tempo , Estados UnidosRESUMO
OBJECTIVE: To evaluate the efficacy and efficiency of weight-adjusted threshold levels for 17-hydroxyprogesterone (17-OHP) in screening newborn infants for 21 hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH). DESIGN: Analysis of the number of false-positive reports and diagnoses in infants, of 21-OH-D-CAH with the use of two strategies. Before October 1993, separate criteria for definite abnormal 17-OHP levels were established and implemented for 41,846 infants on the basis of birth weight: either less than 2200 gm (17-OHP level, 90 ng/ml) or 2200 gm or more (40 ng/ml). To reduce the burden of follow-up testing in low birth weight infants, criteria for definite abnormal 17-OHP results were statistically determined for four, rather than two, birth weight divisions: 1299 gm or less (17-OHP level > or = 165 ng/ml), 1300 to 1600 gm (> or = 135 ng/ml), 1700 to 2200 gm (> or = 90 ng/ml), and more than 2200 gm (> or = 40 ng/ml). These criteria were applied to the next 149,684 infants screened, and rates of false-positive test results and of false-positive diagnoses of 21-OH-D-CAH were compared. RESULTS: Before implementation of four-tiered weight-adjusted 17-OHP criteria, 205 definite abnormal reports yielded four confirmed cases of 21-OH-D-CAH (positive predictive value = 2%; incidence of 21-OH-D-CAH = 1 in 10,461). With the revised criteria, 61 of 149,684 infants had definite abnormal results and 14 cases of 21-OH-D-CAH were confirmed (positive predictive value, 20%; incidence of 21-OH-D-CAH, 1 in 10,692). No undetected severe cases of 21-OH-D-CAH have been subsequently reported. CONCLUSIONS: Weight-adjusted criteria for 17-OHP levels in screening for 21 -OH-D-CAH markedly reduced the number of false-positive results requiring immediate follow-up testing, particularly among low birth weight infants. Increased specificity afforded by these criteria was not accompanied by diminished sensitivity in detecting severe cases. Long-term follow-up of this screened cohort will determine whether the goals of newborn screening for 21-OH-D-CAH are adequately and efficiently fulfilled by this approach.
Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Recém-Nascido/sangue , Triagem Neonatal/métodos , Hiperplasia Suprarrenal Congênita/sangue , Peso Corporal , Reações Falso-Positivas , Humanos , Recém-Nascido de Baixo Peso/sangueRESUMO
Current data on patients treated with human growth hormone (GH) were analyzed for the following safety topics. New leukemia. Thirteen of 46 new cases of leukemia were in non-Japanese patients without risk factors for leukemia (compared with at least 13 new cases expected). A possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors. Nonleukemic extracranial neoplasms. The number of cases reported (10) does not differ significantly from the number expected. Acute pancreatitis. In five of the seven cases reported risk factors (renal failure, valproic acid use, insulin-dependent diabetes mellitus) were present. The available data do not indicate a clear cause-and-effect relation between GH therapy and pancreatitis. Prepubertal gynecomastia. Of 15 possible cases, two were pubertal, eight resolved or improved with continued GH therapy, and two resolved with the cessation of GH therapy. An effect of GH treatment on prepubertal gynecomastia remains unknown. Scoliosis. Scoliosis is reported in fewer than 1 percent of the patients in the National Cooperative Growth Study (general-population prevalence, 1.5% to 3%). Curvature progression can occur during growth acceleration, and a causal association with GH treatment is not substantiated. Pigmented nevi. Nevi growth may be increased with GH treatment. Biopsies have detected no neoplasia or premalignant nevi transformations.
Assuntos
Hormônio do Crescimento/efeitos adversos , Adolescente , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Criança , Pré-Escolar , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/epidemiologia , Hormônio do Crescimento/uso terapêutico , Ginecomastia/epidemiologia , Humanos , Masculino , Nevo Pigmentado/epidemiologia , Pancreatite/epidemiologia , Escoliose/epidemiologia , Síndrome de Turner/epidemiologiaRESUMO
Children with short stature, slowed linear growth velocity, and delayed skeletal maturation may secrete growth hormone (GH) normally in response to provocative stimuli but may also have spontaneous undersecretion of GH. Orally administered clonidine, an alpha 2-adrenergic agonist, is a potent acute stimulator of growth hormone releasing hormone-mediated pituitary GH release. We performed a double-blind, placebo-controlled crossover study of nightly oral clonidine therapy (0.1 mg/m2) in 10 short, slowly growing, non-GH-deficient (stimulated GH level > 15 micrograms/L) prepubertal boys (range, 6.1 to 12.2 years; mean height standard deviation score, -2.3 +/- 0.4). Results of 6 months of clonidine therapy were compared with the results of 6 months of placebo therapy; GH responsiveness was subsequently assessed in 7 of 10 patients. Growth velocity (4.9 +/- 0.6 cm/yr baseline) was not improved by clonidine (4.6 +/- 1.2 cm/yr) or placebo (5.2 +/- 1.2 cm/yr), but it increased (p < 0.001) with GH therapy (8.2 +/- 1.3 cm/yr). Clonidine therapy similarly did not significantly affect plasma levels of insulin-like growth factor I or bone age maturation. Diminution in clonidine-stimulated peak GH levels was not observed after long-term oral clonidine therapy. Thus, in contrast to previous non-placebo-controlled studies, nightly clonidine therapy did not increase growth velocity or plasma insulin-like growth factor I levels. Subsequent acceleration in growth velocity during GH therapy suggests that a proposed increase in clonidine-induced endogenous GH secretion does not result in an effective growth-promoting stimulus.