RESUMO
AIM: To evaluate melatonin secretion in a group of untreated and treated male growth hormone (GH)-deficient children and adolescents. METHODS: We studied 44 male subjects: 8 untreated GH-deficient patients (GHDnt), 16 treated GH-deficient patients (GHDt) and 20 healthy children and adolescents as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24-hour samples), nocturnal (18.00-8.00 h) and diurnal samples (8.00-18.00 h). Levels of 6-SM were expressed as micrograms excreted per time interval and x0394; values (difference between nighttime and daytime values). RESULTS: Significant differences were observed among the 3 groups of pediatric subjects studied for total 6-SM (p < 0.0001), nocturnal 6-SM (p < 0.0001) and x0394; values (p < 0.0001). Subsequent analysis showed significantly higher levels for total 6-SM, nocturnal 6-SM and nighttime-daytime x0394; in the CG versus the GHDnt (p < 0.01) and in the CG versus the GHDt group (p < 0.01). No significant correlations were found between 6-SM excretion and insulin-like growth factor-1 values in the children and adolescents studied. CONCLUSIONS: GH-deficient patients showed lower levels of 6-SM. Our findings provide a different insight to a further understanding of some chronobiological disorders involved in GH deficiency in children.
Assuntos
Hormônio do Crescimento Humano/deficiência , Melatonina/análogos & derivados , Adolescente , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Ritmo Circadiano , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/urina , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/urina , Masculino , Melatonina/urina , Proteínas Recombinantes/uso terapêuticoRESUMO
O hormônio de crescimento urinário (U-GH) noturno foi determinado durante três noites consecutivas em 40 crianças normais, voluntárias, com estatura entre os percentis 10 e 90 e em 29 crianças com estatura abaixo do terceiro percentil, diagnosticadas como baixa estatura constitucional e/ou familial (BEC) ou deficientes de GH (DGH) de acordo com os critérios diagnósticos clássicos. O U-GH foi também determinado durante a realizaçäo dos testes farmacológicos (hipoglicemia ou L-dopa) nas crianças com baixa estatura. Observou-se uma grande variabilidade inter e intra-individual (CV=38 por cento) na excreçäo do U-GH, tanto em crianças normais quanto em crianças com BEC e com DGH. Näo houve diferença entre o sexo masculino e o feminino nas concentraçöes do U-GH (3,1 x 3,6 ng/noite, NS). Os púberes apresentaram maior excreçäo que os impúberes (4,1 x 2,3 ng/noite, p<0,01) e observou-se uma correlaçäo positiva do U-GH com idade (r=0,28, p<0,005). As crianças com DGH apresentaram menor excreçäo de U-GH que crianças normais impúberes (1,1 x 2,2 ng/noite, p<0,0005) e que crianças com BEC (1,1 x 2,2 ng/noite, p<0,001), porém näo houve completa discriminaçäo entre os três grupos. A sensibilidade e especificidade diagnósticas foram respectivamente de 81 por cento e 69 por cento para um ponto de corte de 1,6 ng/noite. Houve correlaçäo positiva entre o U-GH noturno e a resposta do GH plasmático aos testes farmacológicos (r=0,67, p<0,0001), porém a determinaçäo do U-GH durante os testes nao auxiliou na discriminaçäo dos grupos. Considerando determinados pontos de corte (1,2 e 2,5 ng/noite) e coleta de três amostras consecutivas, acreditamos que o método pode ser utilizado como "screening" na avaliaçäo da baixa estatura, reduzindo a indicaçäo de testes farmacológicos.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Estatura , Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento Humano/urina , Transtornos do Crescimento/urina , Hormônio do Crescimento Humano/deficiênciaRESUMO
The effects of growth hormone (GH) deficiency and recombinant human GH replacement (0.6 IU/kg per week) on bone and mineral metabolism in 26 GH-deficient children were studied for 12 months. Before therapy, all children had significantly reduced serum levels of osteocalcin, carboxyl-terminal propeptide of procollagen type I, and 1,25-dihydroxyvitamin D, whereas serum ionized calcium, phosphate, intact parathyroid hormone, calcitonin, and 25-hydroxyvitamin D concentrations were in the normal range. All children had significant reduction of bone density for their chronologic, statural, and bone ages. During therapy with recombinant human GH, a decrease of serum ionized calcium levels and increases of phosphate, osteocalcin, carboxyl-terminal propeptide of procollagen type I, and intact serum levels of parathyroid hormone were found. A significant increase of serum levels of 1,25-dihydroxyvitamin D was found at 12 months. The urinary phosphate/urinary creatinine ratio decreased, whereas values for nephrogenous cyclic adenosine monophosphate and the ratio of the maximum rate of renal tubular reabsorption of phosphate to the glomerular filtration rate increased. Bone density significantly improved at 12 months, with a complete recovery in 12 children (46.2%). Significant relationships were found among growth velocity, bone density, maximum tubular reabsorption/glomerular filtration rate ratio, and serum levels of carboxyl-terminal propeptide of type I procollagen. The changes in serum levels of this propeptide during the first week of recombinant human GH treatment were positively related to growth velocity at 6 and 12 months and to bone density at 12 months of treatment, whereas the changes in osteocalcin levels were not. We conclude that recombinant human GH treatment caused significant modifications of mineral metabolism and significantly increased bone density, and that measurement of serum levels of the propeptide during the first week of recombinant human GH administration may be a useful tool in predicting improved growth velocity and bone density during long-term recombinant human GH replacement.
Assuntos
Osso e Ossos/metabolismo , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/metabolismo , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/uso terapêutico , Minerais/metabolismo , Densidade Óssea/efeitos dos fármacos , Calcitriol/sangue , Cálcio/sangue , Cálcio/urina , Criança , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Transtornos do Crescimento/sangue , Transtornos do Crescimento/urina , Humanos , Masculino , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Fosfatos/sangue , Fosfatos/urina , Pró-Colágeno/sangue , Proteínas Recombinantes , Fatores de TempoRESUMO
We studied the effects of 9 months of treatment with twice-daily subcutaneous injections of insulin-like growth factor I (IGF-I), 120 micrograms/kg per dose, in a 9.7-year-old child with growth hormone insensitivity syndrome, in whom short-term studies had suggested that IGF-I might promote linear growth. Height velocity increased from 6.5 cm/yr (+1.7 SD score) to 11.4 cm/yr (+8.8 SD score). Serum concentrations of IGF-I increased from pretreatment values of 9 +/- 2 micrograms/L to a peak of 347 +/- 26 micrograms/L after 2 hours. Serum concentrations of IGF-II were unchanged. Basal but not stimulated growth hormone concentrations were decreased. During the first 12 days of treatment, serum concentrations and the 24-hour urinary excretion of urea nitrogen were decreased by 28% and 10%, respectively (p < 0.05), there was a 2.4-fold increase in urinary excretion of calcium (p < 0.001), and creatinine clearance and urine volume increased by 22% and 55%, respectively (p < 0.02). The changes in serum levels of urea nitrogen and in urinary calcium and creatinine clearance were still evident at 10 weeks. Fasting and postprandial serum glucose concentrations remained normal. We conclude that IGF-I given as twice-daily subcutaneous injections is effective in stimulating statural growth without producing the hypoglycemia and hyperglycemia observed when IGF-I is infused continuously.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Fator de Crescimento Insulin-Like I/uso terapêutico , Glicemia/análise , Criança , Crescimento/efeitos dos fármacos , Transtornos do Crescimento/sangue , Transtornos do Crescimento/urina , Hormônio do Crescimento/sangue , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like II/análise , Masculino , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Ureia/sangue , Ureia/urinaRESUMO
Thirty-five children with short-stature underwent insulin-loading and sleep tests for assessment of secretion of human growth hormone. Correlations between the levels of human growth hormone in the serum and urine during the tests were examined to elucidate the clinical significance of urinary human growth hormone levels in short children. The concentration and total amount of human growth hormone in the urine correlated significantly with the peak concentration of serum human growth hormone (r = 0.81, p less than 0.001 and r = 0.80, p less than 0.001, respectively) and the integrated concentration of human growth hormone (r = 0.85, p less than 0.001 and r = 0.85, p less than 0.001, respectively) in the insulin-loading test. The concentration and total amount of human growth hormone in the morning urine also correlated significantly with the peak concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.70, p less than 0.001, respectively) and the integrated concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.72, p less than 0.001, respectively) in the sleep test. The concentration or total amount of human growth hormone in the urine differed significantly among children with human growth hormone deficiency, those with nonendocrine short stature, and those with normal stature (p less than 0.05). These data suggest that measurement of human growth hormone in the urine may be used to assess secretion of human growth hormone, serving as a screening test for human growth hormone deficiency in children.