RESUMO
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 assess the clinical utility of growth-hormone-binding protein (GHBP), along with growth hormone (GH), insulin-like growth factor I (IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3), levels in the evaluation of short stature. STUDY DESIGN: Prospective substudy of the National Cooperative Growth Study, a multicenter observational study. RESULTS: A total of 6447 assessable subjects undergoing workup for short stature were enrolled at 197 sites. At baseline the cause of short stature was undefined in 77% of subjects. Mean GHBP levels were lowest in subjects with renal disease and highest in those with Turner syndrome. No cases of complete GH insensitivity syndrome (Laron syndrome) were identified. Subjects with low GHBP levels were among those tested for GH receptor mutations. IGF-I standard deviation scores (SDS) and IGFBP-3 SDS were positively correlated; both increased during GH therapy. There was a weak positive correlation between log peak GH levels and both IGF-I SDS and IGFBP-3 SDS and a weak negative correlation between log peak GH levels and GHBP SDS. Mean changes in GHBP SDS in subjects treated with GH and untreated subjects were not significant. Change in height SDS in subjects treated with GH was negatively correlated with age and IGF-I level but not correlated with baseline GHBP SDS. CONCLUSION: GHBP levels are GH independent and not predictive of responses to GH therapy, although low GHBP levels may indicate GH receptor abnormalities and partial GH insensitivity.
Assuntos
Proteínas de Transporte/sangue , Transtornos do Crescimento/sangue , Hormônio do Crescimento Humano/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fatores Etários , Estatura/efeitos dos fármacos , Canadá , Criança , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Previsões , Crescimento/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/genética , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Nefropatias/sangue , Masculino , Mutação/genética , Estudos Prospectivos , Receptores da Somatotropina/genética , Síndrome , Síndrome de Turner/sangue , Estados UnidosRESUMO
As of October 1993 the National Cooperative Growth Study included 1262 children with brain tumor who were treated with growth hormone. The type of brain tumor was specified in 947 (75%) of these children. The most common types were glioma, medulloblastoma, and craniopharyngioma, accounting for 91.3% of all those for which type was specified. Brain tumor recurred in 83 (6.6%) of the 1262 children over a total of 6115 patient-years at risk. The frequencies of tumor recurrence in children with low-grade glioma (18.1%), medulloblastoma (7.2%), and craniopharyngioma (6.4%) are lower than those in published reports of tumor recurrence in the general pediatric population with the same types of tumors. The analysis cannot conclusively show that no increased risk of tumor recurrence exists, however, because of the potential incompleteness of data reporting in the National Cooperative Growth Study. Nevertheless the findings are reassuring that children with the more common types of brain tumor who are treated with growth hormone do not seem to be at excessive risk for tumor recurrence.
Assuntos
Neoplasias Encefálicas/epidemiologia , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/efeitos adversos , Hormônio do Crescimento/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos , Neoplasias Encefálicas/diagnóstico , Criança , Pré-Escolar , Bases de Dados Factuais , Transtornos do Crescimento/etiologia , Humanos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: To determine whether some patients with idiopathic short stature have partial resistance to growth hormone (GH). Patients with idiopathic short stature have decreased serum levels of the GH receptor-related GH-binding protein (GHBP), and low GHBP levels are associated with complete GH insensitivity (Laron) syndrome. We hypothesized that patients with idiopathic short stature and low GHBP levels may also have a degree of GH insensitivity. DESIGN: Retrospective analysis of patients in a multicenter study. SETTING: Ninety-six National Cooperative Growth Study centers in the United States and Canada. SUBJECTS: Five hundred eleven patients with idiopathic short stature who were treated with GH. All patients had a baseline height standard deviation score of less than -2 and a maximum stimulated GH level greater than 10 micrograms/L. Of these, 101 (20%) had a baseline GHBP standard deviation score of -2 or less. RESULTS: The patients with low GHBP levels, in comparison with those with normal GHBP levels, had a lower mean extracted standard deviation score for insulin-like growth factor I (-3.3 +/- 1.1 vs -2.5 +/- 1.4; p < 0.0001) but mean 12-hour GH values (2.8 +/- 1.1 vs 2.3 +/- 1.1 micrograms/L; p <0.0001). The differences between groups were statistically significant after control for age and weight-for-height standard deviation score. Among prepubertal patients, there was no significant difference between the low and normal GHBP groups in mean pretreatment or first-year growth rate (p = 0.74, 0.61 respectively) with comparable doses of GH. CONCLUSIONS: Patients with idiopathic short stature and low GHBP levels, compared with those with normal GHBP levels, had significantly lower standardized levels of insulin-like growth factor I, and higher mean 12-hour GH levels, which suggest partial GH insensitivity. There was no significant correlation of GHBP levels with the growth response to exogenous GH.