RESUMO
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
We investigated the mechanisms by which androgens increase mean circulating GH concentrations in boys. We tested two hypotheses: 1) testosterone increases serum GH concentrations at least in part via an androgen receptor-mediated mechanism, rather than exclusively by way of aromatization to estrogen; 2) androgen augments one or more specific features to GH secretion (secretory burst number, amplitude, and/or duration) and/or prolongs the half-life of GH removal. To examine these hypotheses, prepubertal boys with constitutionally delayed development and/or growth were given injections of testosterone (100 mg monthly; n = 7) or treated with oral oxandrolone, a nonaromatizable androgen (1.25 mg twice daily; n = 5). Pulsatile GH release was studied before and during androgen administration by sampling blood at 20-min intervals for 24 h. The immunoreactive GH time series were subjected to a novel deconvolution technique, which revealed that 1) testosterone and oxandrolone each increased mean (24-h) serum GH concentrations significantly; 2) both androgens augmented the daily endogenous GH secretory rate significantly; 3) increased GH production resulted from a higher mass of GH secreted per burst and a higher maximal rate of GH secretion within each burst; and 4) androgens amplified the magnitude of the nyctohemeral rhythm in the mass (but not frequency) of GH secretory pulses. The observed effects of androgen were specific, since the number and duration of GH secretory bursts and the subject-specific GH half-life were unaltered by androgen treatment. We conclude that androgen acting apart from conversion to estrogen is capable of specifically activating the somatotropic axis via distinct neuroendocrine secretory mechanisms.
Assuntos
Hormônio do Crescimento/metabolismo , Oxandrolona/farmacologia , Testosterona/farmacologia , Adolescente , Ritmo Circadiano/efeitos dos fármacos , Hormônio do Crescimento/sangue , Meia-Vida , Humanos , Masculino , Puberdade Tardia/metabolismo , Taxa Secretória/efeitos dos fármacosRESUMO
Sera from 438 children were examined for autoantibodies to thyroid microsomes, thyroglobulin, pancreatic islet cells, gastric parietal cells, and adrenocortical cells by indirect hemagglutination and immunofluorescence techniques. A modification of the indirect hemagglutination technique allowed specific detection of low titers of antithyroidal antibodies. The subjects included a control group (117) with no known autoimmune disease, and children with disorders of the thyroid (88), insulin-dependent diabetes mellitus (201), Turner's Syndrome (24), and Addison disease (8). A subject's age at the time of disease onset and the race and sex were correlated with the prevalence of autoantibodies. The coincidence of autoantibodies to components of the thyroid with autoantibodies to gastric parietal cells was increased in children with disorders of the thyroid (94%, 18/19) over that observed in diabetes (29%, 4/14), Turner syndrome (0%), or Addison disease (0%), perhaps indicating different genetic propensities for the development of parietal cell antibodies in these groups. Islet cell antibodies were not found in subjects with Turner syndrome, nor were they more prevalent in white or black subjects with diabetes. The incidence of organ-specific autoantibodies in individuals without overt clinical disease may reflect an altered immunologic state that will lead eventually to autoimmune disease. Islet cell antibodies decline in prevalence in diabetes, whereas thyroid antibodies in disorders of the thyroid do not; this may reflect differences in the pathogenesis of these common autoimmune endocrine disorders in children.
Assuntos
Autoanticorpos/análise , Doenças do Sistema Endócrino/imunologia , Especificidade de Órgãos , Doença de Addison/imunologia , Adolescente , Glândulas Suprarrenais/imunologia , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/imunologia , Feminino , Imunofluorescência , Mucosa Gástrica/imunologia , Testes de Hemaglutinação , Humanos , Lactente , Ilhotas Pancreáticas/imunologia , Masculino , Doenças da Glândula Tireoide/imunologia , Glândula Tireoide/imunologia , Síndrome de Turner/imunologiaAssuntos
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
Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal...
Assuntos
Lipodistrofia/congênito , Adolescente , Hormônio Adrenocorticotrópico/metabolismo , Antígenos , Arginina , Glicemia/análise , Criança , Pré-Escolar , Feminino , Glucagon/metabolismo , Teste de Tolerância a Glucose , Hormônio do Crescimento/metabolismo , Hormônios , Humanos , Lactente , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Metabolismo dos Lipídeos , Lipodistrofia/genética , Lipodistrofia/metabolismo , Masculino , TolbutamidaRESUMO
Since 1946 104 children and adolescents with toxic diffuse goiter have been treated. Sixty-seven were treated with a thioamide for more than 12 months. Remission occurred in 61%. Twenty-five patients had a 12-hour perchlorate discharge test to determine the least frequent dose schedule required for disease control: 68% could be controlled on a single daily dose and an additional 25% on an every 12-hour schedule. A one-hour radioiodine uptake on combined therapy and change in thyroid gland size during treatment were found to be highly correlated with the presence of a spontaneous remission. Thirty-six patients have been treated by subtotal thyroidectomy. To date 65% have developed permanent hypothyroidism. In the author's opinion, thoamides are the treatment of choice for the majority of children and adolescents.
Assuntos
Antitireóideos/uso terapêutico , Doença de Graves/tratamento farmacológico , Adolescente , Antitireóideos/efeitos adversos , Carbimazol/uso terapêutico , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Doença de Graves/sangue , Doença de Graves/diagnóstico , Humanos , Masculino , Metimazol/uso terapêutico , Percloratos/uso terapêutico , Propiltiouracila/uso terapêutico , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacos , Tireoidectomia , Tiroxina/sangue , Tiroxina/uso terapêuticoRESUMO
Ninety-eight females with congenital adrenal hyperplasia due to a defect in either the 21-hydroxylase or the 11 beta-hydroxylase enzyme were evaluated to determine the effects of glucocorticoid treatment on growth, pubertal development, and fertility. When treatment was begun prior to one year of age, mean final height was 157.4 +/- 7.3 com, well within the normal adult female range, and significantly (p less than 0.001) greater than the mean final height of 150.9 +/- 4.3 cm found in untreated patients. The mean age of menarche in patients treated prior to the age of six years was 13.8 +/- 3.7 years which is significantly (p less than 0.01) delayed compared to that in the normal population of the United States. However, 92% of patients with menstrual delay had inadequate suppression of adrenal androgens and urinary excretion of 17 ketosteroids larger than 7.0 mg/24hours. The increased production of adrenal androgens was the result of poor compliance or an insufficient prescribed dose of glucocorticoids. The fertility rate in patients first treated between six and 20 years of age was 64%. The excretion of urinary 17 KS at the time of pregnancy was 2.5 to 5.3 mg/24 hours. All of the patients who delivered term infants required delivery by cesarean section because of cephalopelvic disproportion. The major problems encountered in the management of adolescent patients were patient noncompliance and physician failure to increase the glucocorticoid dose as the patient's body size increased.