RESUMEN
CONTEXT: The insulin-like growth factor (IGF) system exerts many effects on the growth and differentiation of both normal and malignant cells. The serum concentrations of insulin-like growth factor I (S-IGF-I), insulin-like growth factor-binding protein 2 (S-IGFBP-2) and insulin-like growth factor-binding protein 3 (S-IGFBP-3) and their inter-relations may differ in certain disease states from those seen in healthy individuals. OBJECTIVE: To estimate age-, gender- and body mass index (BMI)-specific univariate, bivariate and trivariate 95% reference regions for these components in healthy adults and present indices that will facilitate interpretation of patient observations in relation to these reference regions. DESIGN: Blood samples were taken in the morning from 427 healthy, non-fasting German blood donors of both genders (age range, 18-79 years; BMI range, 16-44 kg/m(2)). Reference regions were developed with multivariate regression methods. RESULTS: Regression analyses showed that S-IGF-I and S-IGFBP-3 levels decrease with increasing age, whereas S-IGFBP-2 concentrations increase with age (P<0.0001). Females had significantly higher S-IGFBP-3 levels than males (P<0.0001) and similar S-IGF-I and S-IGFBP-2 concentrations. Increasing BMI was associated with decreasing S-IGFBP-2 (P<0.0001), but was not significantly associated with the concentrations of the other two analytes. Controlling for age, gender and BMI, S-IGF-I and S-IGFBP-3 were positively correlated (r=0.58), whereas S-IGF-I and S-IGFBP-2, and S-IGFBP-2 and S-IGFBP-3 were negatively correlated (r=-0.11 and r=-0.18, respectively). Based on the regression models, which were controlled for age, gender and BMI, two- and three-dimensional 95% reference regions with associated patient indices were described for each pair of analytes and for the trio of analytes, respectively. CONCLUSIONS: The multivariate reference regions developed in this study should be useful in identifying patients with an abnormal IGF-IGFBP axis. It is suggested that introducing multidimensional reference regions and the described patient indices into clinical practice may aid monitoring of the safety of GH therapy. These patient indices may also be useful in the assessment of cancer risk.
Asunto(s)
Envejecimiento/fisiología , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Análisis de Regresión , Factores Sexuales , Adulto JovenRESUMEN
PURPOSE: To evaluate the value of a registry, set in 'real-life practice', as a contribution to evidence-based medicine and to estimate the impact of information collected in such a registry, on the up to date knowledge in growth hormone (GH)-related disorders. METHODS: Analysis of data collected prospectively for a pharmacoepidemiological registry--KIMS (Pfizer International Metabolic Database)--in assessing long-term clinical and safety outcomes of GH treatment (Genotropin) in patients with GH deficiency. The study was based on 11,374 treated (40,000 patient-years of observation) and 263 untreated adult GH deficient patients from 30 countries, in whom background characteristics, clinical values such as lipids and body composition, quality of life (QoL) and GH dosage as well as safety profile were evaluated. Citation analysis for the published papers was also performed. RESULTS: The study depicts the clinical picture of adult patients with GH deficiency managed in current clinical settings. It confirms the features previously detected such as increased cardiovascular risk, mostly dyslipidemia and abnormal body composition as well as impaired QoL. There was considerable heterogeneity of conditions resulting in GH deficiency. The large database also enabled study of rare causes of the condition. The 31 out of 36 KIMS papers were cited 544 times, in 125 different journals. CONCLUSIONS: These findings and the further insight into the response to GH replacement therapy show that the registry methodology is valuable for filling the gaps of information in evidence-based medicine that cannot be addressed by clinical trials.