RESUMO
OBJECTIVE: To carry out a multicenter, prospective, randomized trial of human growth hormone (GH), alone or in combination with oxandrolone (OX), in patients with Turner's syndrome (TS). METHODS: In an initial phase lasting 12 to 24 months, 70 girls with TS, verified by karyotype, were randomly assigned to one of four groups: (1) observation, (2) OX, (3) GH, or (4) GH plus OX. After completion of the first phase, group 3 subjects continued to receive GH only. All other subjects were treated with GH plus OX. Subjects were followed up until attainment of adult height and/or cessation of treatment. Data from this trial were compared with growth characteristics of 25 American historical subjects with TS (matched for age, height, parental target height, and karyotype) who never received either GH or androgens. RESULTS: Of the 70 subjects enrolled, 60 completed the clinical trial. The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4+/-5.5 cm (mean +/- SD), 8.4+/-4.5 cm taller than their mean projected adult height at enrollment (95% confidence interval [CI]: 6.3 to 10.6 cm). The 43 subjects receiving GH plus OX attained a mean height of 152.1+/-5.9 cm, 10.3+/-4.7 cm taller than their mean projected adult height (95% CI: 8.9 to 11.7 cm). The historical control subjects had a mean adult height of 144.2+/-6.0 cm, precisely matching their original projected adult height of 144.2+/-6.1 cm. CONCLUSIONS: GH, either alone or in combination with OX, is capable of stimulating short-term growth and augmenting adult height in girls with TS. With early diagnosis and initiation of treatment, an adult height of more than 150 cm is a reasonable goal for most girls with TS.
Assuntos
Anabolizantes/uso terapêutico , Estatura , Hormônio do Crescimento/uso terapêutico , Oxandrolona/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Estudos Prospectivos , Resultado do Tratamento , Síndrome de Turner/fisiopatologiaRESUMO
Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height. It is yet unknown whether therapy would alter pubertal development or affect final height. Three-year treatment results in a group of children with idiopathic short stature are reported. For year 1 of the study, 121 prepubertal children were randomly selected to receive somatotropin, 0.3 mg/kg per week, administered subcutaneously three times weekly (n = 63), or to be nontreatment control subjects (n = 58). After 1 year, all subjects were again randomly selected to receive either three-times-weekly or daily dosing at the same total dose. For the 92 subjects who completed 36 months of treatment, mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment. Daily dosing resulted in a significantly faster mean growth rate (9.0 cm/yr) than three-times-weekly dosing (7.8 cm/yr) (p = 0.0005). Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3, respectively, and did not differ by dosing group. Mean standardized height for all subjects improved from -2.7 to -1.6 after 3 years. When the growth rate was standardized for bone age, however, subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period (p < 0.02). Mean standardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset, but for individuals this score was more variable. Year-1 growth response, expressed as growth rate or change in height SD score, was the best predictor of growth in subsequent years. Responses to therapy could not be reliably predicted from baseline anthropometric variables, plasma insulin-like growth factor I SD score, growth hormone levels. Final height assessment will be needed to determine the ultimate benefit of therapy.
Assuntos
Estatura/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Puberdade/efeitos dos fármacos , Determinação da Idade pelo Esqueleto , Antropometria , Estatura/fisiologia , Criança , Protocolos Clínicos , Relação Dose-Resposta a Droga , Feminino , Transtornos do Crescimento/fisiopatologia , Humanos , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Prognóstico , Fatores de TempoRESUMO
Demographic, diagnostic, and baseline clinical data were collected for a large cohort (N = 2331) of children who started treatment with biosynthetic human growth hormone (GH) between October 1985 and October 1987. Eighty-one percent met classic criteria for GH deficiency and were classified as having idiopathic GH deficiency (59%), organic GH deficiency (18%), or septo-optic dysplasia (4%). The remaining 19.8% had short stature of varied causes. Height standard deviation score at diagnosis, maximum GH response to stimulation, and heights of parents were examined according to gender, race, age at diagnosis, and previous treatment history. The predominance of boys in all subgroups except septooptic dysplasia, and the observation that girls with idiopathic GH deficiency were comparatively shorter than boys at diagnosis, suggest ascertainment bias. Black children with idiopathic GH deficiency were shorter than white children at diagnosis, and their low overall representation (6.0%) compared with their percentage in the at-risk population (12.9%) also suggest ascertainment bias among races. These data provide a profile of GH deficiency as it is currently defined and expose possible inherent biases in the diagnostic process. Now that GH supply is no longer limited, criteria for its use should be formulated to avoid apparent underascertainment or late diagnosis of GH deficiency in girls and black children.
Assuntos
Hormônio do Crescimento/análogos & derivados , Hormônios/uso terapêutico , Adolescente , Adulto , População Negra , Estatura , Criança , Pré-Escolar , Estudos de Coortes , Demografia , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano , Humanos , Masculino , Vigilância de Produtos Comercializados , Proteínas Recombinantes , Fatores Sexuais , Estados Unidos , População BrancaRESUMO
Seventy girls with Turner syndrome, 4 to 12 years of age, participated in a prospective, randomized study to determine the effects on growth of methionyl human growth hormone (met-hGH) or oxandrolone. Subjects were randomly assigned to receive either no treatment (control) or met-hGH (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination met-hGH plus oxandrolone. At the end of an initial period of 12 to 20 months, patients in the original control and oxandrolone groups were given combination met-hGH plus oxandrolone. At that time the dosage of oxandrolone was lowered to 0.0625 mg/kg/day. Sixty-five subjects have now completed the first 3 years of the study. Compared with the control growth rate for year 1 (3.8 cm/yr), significant increases in growth rate were seen in all 3 years of combination therapy (9.8, 7.4, and 6.1 cm/yr, respectively) and in the first 2 years of treatment with met-hGH alone (6.6, 5.4, and 4.6 cm/yr). When growth velocity was expressed as standard deviation for age in girls with Turner syndrome, significant increases relative to the control group for year 1 (-0.1 SD) were seen in all three years of both combination therapy and met-hGH alone (combination, +6.6, +4.3, +3.0 SD; met-hGH, +3.1, +2.0, +1.4 SD). After 3 years of treatment, predicted adult height by the method of Bayley-Pinneau increased 4.5 cm in the met-hGH group and 8.2 cm in the combination group.
Assuntos
Hormônio do Crescimento/análogos & derivados , Hormônios/uso terapêutico , Oxandrolona/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Estatura , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Crescimento/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/uso terapêutico , Hormônios/administração & dosagem , Hormônio do Crescimento Humano , Humanos , Oxandrolona/administração & dosagem , Estudos Prospectivos , Distribuição AleatóriaRESUMO
To evaluate the effects of growth-promoting therapy on carbohydrate metabolism in girls with Turner syndrome, we determined glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) at baseline and after 5 days, 2 months, and 12 months of treatment with growth hormone (GH), oxandrolone, or a combination of GH and oxandrolone, or after the same intervals with no therapy. Before therapy, subjects had a significantly greater glucose response during OGTT than published normal control values. There were no significant changes in mean fasting glucose, cholesterol, or triglyceride concentrations in any of the treatment groups. The integrated glucose concentrations rose significantly over baseline values in the oxandrolone group at 2 and 12 months and in the combination group at 5 days. There were significant increases in the mean integrated insulin concentrations at 2 and 12 months for the group receiving oxandrolone alone and at all three times for the group receiving combination therapy. Thus oxandrolone, alone or in combination with GH, had significant effects on carbohydrate metabolism in subjects with Turner syndrome, whereas GH alone did not.
Assuntos
Metabolismo dos Carboidratos , Hormônio do Crescimento/uso terapêutico , Metabolismo dos Lipídeos , Oxandrolona/uso terapêutico , Síndrome de Turner/metabolismo , Glicemia/análise , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Síndrome de Turner/sangue , Síndrome de Turner/tratamento farmacológicoRESUMO
Seventy girls with Turner syndrome, 4 to 12 years of age, were randomly assigned to receive either no treatment (control) or methionyl human growth hormone (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination hGH plus oxandrolone therapy. Baseline growth rates averaged 4.3 cm/yr, and all were within 2 SD of mean growth velocity for age in girls with Turner syndrome. Sixty-seven girls remained in the study for a minimum of 1 year. Growth rates and growth velocity (in standard deviations for age in girls with Turner syndrome) were control 3.8 cm/yr (-0.1 SD), hGH 6.6 cm/yr (+2.3 SD), oxandrolone 7.9 cm/yr (+3.7 SD), and combination therapy 9.8 cm/yr (+5.4 SD). Mean bone ages advanced 1.0 years (hGH), 1.3 years (oxandrolone), and 1.6 years (combination). However, median increments in height age/bone age (delta HA/delta BA) ratios ranged from 1.0 to 1.1 for treatment groups, compared with 0.8 for the controls. Predicted adult height by the method of Bayley-Pinneau increased 2.5 cm for hGH or oxandrolone alone, and 3.2 cm for combination treatment. These data indicate that both hGH and oxandrolone can significantly stimulate short-term skeletal growth in patients with Turner syndrome, and potentially increase final adult height.
Assuntos
Hormônio do Crescimento/análogos & derivados , Hormônios/uso terapêutico , Oxandrolona/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Adolescente , Adulto , Determinação da Idade pelo Esqueleto , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Feminino , Crescimento/efeitos dos fármacos , Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I/sangue , Estudos Prospectivos , Distribuição AleatóriaAssuntos
Anormalidades Múltiplas , Craniofaringioma/complicações , Transtornos do Crescimento/complicações , Neoplasias Hipofisárias/complicações , Criança , Pré-Escolar , Disostose Craniofacial/complicações , Craniofaringioma/cirurgia , Feminino , Retardo do Crescimento Fetal/complicações , Hormônio do Crescimento/deficiência , Humanos , Lactente , Recém-Nascido , Masculino , Desenvolvimento Maxilofacial , Neoplasias Hipofisárias/cirurgia , Gravidez , SíndromeAssuntos
Lipodistrofia/congênito , Síndrome do Ovário Policístico/etiologia , Criança , Feminino , Humanos , Lipodistrofia/complicações , Ovário/fisiopatologia , Testes de Função Adreno-Hipofisária , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/cirurgiaRESUMO
A distinct syndrome is delineated on the basis of two previously reported and one newly described case. The syndrome combines multiple congenital anomalies with a progressive skeletal dysplasia-dysostosis, The gradual evolution of the skeletal disorder is demonstrated in the present patient. It will now be possible to diagnose this syndrome at birth.