Assuntos
Hipotireoidismo , Recém-Nascido Prematuro , Tireotropina/sangue , Tiroxina/uso terapêutico , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/mortalidade , Recém-Nascido , Fatores de Risco , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologiaRESUMO
OBJECTIVE: To evaluate the effect of growth hormone (GH) therapy on pubertal onset, pubertal pace, adult testicular function, and adrenarche in boys with non-GH-deficient short stature. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. GH (0.074 mg/kg, subcutaneously, 3 times per week) or placebo treatment was initiated in prepubertal or early pubertal boys and continued until near final height was reached (n = 49). Statistical significance was assessed by survival analysis, repeated-measures analysis of variance, and Student t test. RESULTS: GH therapy did not affect the age at pubertal onset, defined either by testicular volume >4 mL or by testosterone concentration >1.0 nmol/L (30 ng/dL). GH treatment also did not affect the pace of puberty, defined either by the rate of change in testicular volume or testosterone concentration during the 4 years after pubertal onset. In boys followed up to age > or =16 years during the study, there were no significant differences in final testicular volume or in plasma testosterone, luteinizing hormone, or follicle-stimulating hormone concentrations. The pace of adrenarche, assessed by change in dehydroepiandrosterone sulfate levels over time, also did not differ significantly between the GH and placebo groups. CONCLUSION: Our findings suggest that GH treatment does not cause testicular damage, alter the onset or pace of puberty, or alter the pace of adrenarche in boys with non-GH-deficient short stature.
Assuntos
Nanismo/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Puberdade/efeitos dos fármacos , Testículo/efeitos dos fármacos , Adolescente , Idade de Início , Análise de Variância , Criança , Sulfato de Desidroepiandrosterona/sangue , Método Duplo-Cego , Humanos , Masculino , Análise de Sobrevida , Testosterona/sangueRESUMO
OBJECTIVE: Hypothalamic obesity is a rare sequela of cranial insult, for which pathogenesis and treatment remain obscure. In rodents ventromedial hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin resistance. Reduction of insulin secretion in humans may attenuate weight gain. METHODS: Eight children with intractable obesity after therapy for leukemia or brain tumors underwent oral glucose tolerance testing (OGTT) with simultaneous insulin levels before and after treatment with octreotide for 6 months. RESULTS: In comparison with a 6-month pre-study observation period, patients exhibited weight loss (+6.0 +/- 0.7 kg vs -4.8 +/- 1.8 kg; P =.04) and decrease in body mass index (+2.1 +/- 0.3 kg/m(2) vs -2.0 +/- 0.7 kg/m(2); P =.0001). Recall calorie count decreased during the 6 months of treatment (P =. 015). OGTT demonstrated biochemical glucose intolerance in 5 of 8 patients initially and in 2 of 7 at study end, whereas insulin response was decreased (281 +/- 47 microU/mL vs 114 +/- 35 microU/mL; P =.04). Percent weight change correlated with changes in insulin response (r = 0.72, P =.012) and changes in plasma leptin r = 0.76, P =.0004). CONCLUSIONS: Patients with hypothalamic obesity demonstrate excessive insulin secretion. Octreotide administration promoted weight loss, which correlated with reduction in insulin secretion on OGTT and with reduction in leptin levels. Pre-study biochemical glucose tolerance improved in several patients while they were receiving octreotide. These results suggest that normalization of insulin secretion may be an effective therapeutic strategy in this syndrome.
Assuntos
Dano Encefálico Crônico/complicações , Hormônios/uso terapêutico , Doenças Hipotalâmicas/tratamento farmacológico , Obesidade/tratamento farmacológico , Octreotida/uso terapêutico , Somatostatina/agonistas , Adolescente , Animais , Criança , Modelos Animais de Doenças , Feminino , Humanos , Hiperfagia/tratamento farmacológico , Hiperfagia/etiologia , Hiperfagia/fisiopatologia , Doenças Hipotalâmicas/etiologia , Doenças Hipotalâmicas/fisiopatologia , Insulina/sangue , Masculino , Obesidade/etiologia , Obesidade/fisiopatologia , RatosRESUMO
To study the effect of delaying epiphyseal fusion on the growth of GH-deficient children, we studied 14 pubertal, treatment naive, GH-deficient patients (6 girls and 8 boys) in a prospective, randomized, placebo-controlled trial. Chronological age was 14.5 +/- 0.5 yr, and bone age was 11.6 +/- 0.3 yr (mean +/- SEM) at the beginning of the study. Patients were assigned randomly to receive GH and LH-releasing hormone (LHRH) analog (n = 8) or GH and placebo (n = 6) during 3 yr, with planned continuation of GH treatment until epiphyseal fusion. Patients were measured with a stadiometer and had serum LHRH tests, serum testosterone (boys), serum estradiol (girls), and bone age performed every 6 months. Patients treated with GH and LHRH analog showed a clear suppression of their pituitary-gonadal axis and a marked delay in bone age progression. We observed a greater gain in height prediction in these patients than in the patients treated with GH and placebo after 3 yr of treatment (mean +/- SEM, 14.0 +/- 1.6 vs. 8.0 +/- 2.4 cm; P < 0.05). These preliminary findings suggest that delaying epiphyseal fusion with LHRH analog in pubertal GH-deficient children treated with GH increases height prediction and may increase final height compared to treatment with GH alone.
Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Puberdade/efeitos dos fármacos , Adolescente/fisiologia , Determinação da Idade pelo Esqueleto , Estatura/efeitos dos fármacos , Feminino , Crescimento/efeitos dos fármacos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Sixty-eight percent of pediatric sulfonylurea ingestions reported to poison centers do not result in laboratory or behavioral effects. Consequently, if all exposed children are admitted overnight or for 24 hours for these exposures, it will result in 600 to 700 hospital admissions per year of children who will remain free of symptoms. We prospectively studied exposures reported to 10 regional poison centers to determine if it were possible to differentiate those patients who would have symptoms from those who would remain symptom free. METHODS: We analyzed all sulfonylurea exposures in children < or = 12 years old reported to the participating poison centers. Hypoglycemia was defined as blood glucose (BG) concentration < 60 mg/dl. RESULTS: Hypoglycemia developed in 56 (30%) of 185 exposed patients. Fifty-four of the 56 (96%) hypoglycemic patients had development of hypoglycemia within 8 hours of ingestion. Eighty-seven of the patients were initially managed with oral supplementation only; in 13 cases, treatment advanced to intravenous administration of glucose or glucagon with the onset of hypoglycemia. There was no statistical difference in medical outcome between patients monitored during oral supplementation versus during intravenous infusion of dextrose. Ingestions analyzed by time of day did not predict risk of hypoglycemia. Sufficient data were available for 103 (58%) of the 177 patients who ingested glyburide or glipizide to calculate a toxic dose/weight ratio. Of these 103 patients, 31 of 36 patients who ingested < or = 0.3 mg/kg remained symptom free, whereas 31 of 67 who ingested more than 0.3 mg/kg had BG concentrations < 60 mg/dl (p < 0.005, 95% confidence interval 0.05 to 0.58; sensitivity 86%, specificity 46%). CONCLUSION: A lack of onset of hypoglycemia (BG > 60 mg/dl) in the first 8 hours after ingestion is predictive of a benign outcome in accidental pediatric sulfonylurea ingestion. Clinical observation of children for onset of hypoglycemia during oral feeding alone appears safe. Some children with symptoms of hypoglycemia need to receive intravenous dextrose therapy. Time of day of ingestion is not predictive of risk of hypoglycemia. Finally, at this time it appears inappropriate to use a milligram per kilogram body weight dose as a guide for management decisions.
Assuntos
Hipoglicemia/induzido quimicamente , Hipoglicemiantes/intoxicação , Compostos de Sulfonilureia/intoxicação , Acidentes , Administração Oral , Glicemia/análise , Peso Corporal , Criança , Pré-Escolar , Intervalos de Confiança , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Previsões , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Glipizida/intoxicação , Glucagon/administração & dosagem , Glucagon/uso terapêutico , Glucose/administração & dosagem , Glucose/uso terapêutico , Glibureto/intoxicação , Hospitalização , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemia/fisiopatologia , Lactente , Infusões Intravenosas , Masculino , Admissão do Paciente , Centros de Controle de Intoxicações , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fatores de Tempo , Resultado do TratamentoRESUMO
A 16-year-old boy with short stature and mild primary hypothyroidism received subcutaneous injections of either recombinant human growth hormone or placebo in diluent that contained glycerol and m-cresol as a preservative. While he was receiving the study drug, myalgia developed and serum creatine kinase values were elevated. Both resolved when injections were stopped and recurred when injections of diluent alone were given. The myalgia and elevated creatine kinase activity were apparently caused by a component of the diluent.
Assuntos
Creatina Quinase/sangue , Cresóis/efeitos adversos , Doenças Musculares/induzido quimicamente , Dor/induzido quimicamente , Conservantes Farmacêuticos/efeitos adversos , Adolescente , Hormônio do Crescimento/administração & dosagem , Humanos , Injeções Subcutâneas , Masculino , Doenças Musculares/enzimologia , Dor/enzimologiaRESUMO
Because some patients with growth hormone (GH) deficiency are found to be hypothyroid after initiation of treatment with GH, we assessed the predictive value of the nocturnal thyrotropin surge (a sensitive test for central hypothyroidism) in 56 untreated GH-deficient children and adolescents. Eighteen patients had a subnormal thyrotropin surge (mean 18% (range -30% to 46%)), significantly less than that of 96 normal control subjects (mean 124%; 95% confidence limits, 47% to 300%; p less than 0.01); 13 of the 18 had a subnormal total thyroxine (T4) level or a subnormal free T4 level, or both. These 18 patients were given thyroid hormone replacement therapy; GH deficiency was confirmed during treatment with thyroxine. Of the remaining 38 patients, who had no initial evidence of dysfunction of the hypothalamic-pituitary-thyroid axis, 23 were re-examined while they were receiving GH treatment. Hypothyroidism developed in none of those 23 children during GH therapy. The nocturnal thyrotropin surge test and determination of iodothyronine levels were repeated in 14 of these euthyroid patients. There was no significant change in mean thyrotropin surge (129% (range +49% to +300) vs 125% (range +51% to +222%)), mean serum level of total T4 (111 +/- 4 vs 103 +/- 3 nmol/L), mean serum level of free T4 (19 +/- 0.7 vs 18 +/- 0.8 pmol/L), mean serum level of triiodothyronine (2.5 +/- 0.1 vs 2.5 +/- 0.1 nmol/L), or mean serum level of thyrotropin (2.9 +/- 0.3 vs 2.9 +/- 0.5 mU/L (mean +/- SEM)). We conclude that GH treatment does not appreciably alter thyroid function in GH-deficient patients who have no evidence of thyroid axis dysfunction before GH treatment.