RESUMEN
BACKGROUND: In 2005, a special survey in the Belgian External Quality Assessment focused on the performance of six automated immunoassay analysers most frequently used in Belgium for estradiol-17beta (E(2)) and progesterone. Results obtained were compared with values determined by reference method, isotope dilution-gas chromatograph/mass spectrometry (ID-GC/MS). METHODS: Five fresh frozen serum samples, without additives, from single donors and three pools from pregnant women were distributed to all registered Belgian laboratories. Total variation, bias, linear relationship within the reported range and linear regression were investigated. RESULTS: Inter-laboratory coefficients of variation ranged from 4 to 49% for E(2) and from 6 to 45% for progesterone. Bias ranged from -26 to 239% for E(2) and from -23 to 81% for progesterone. Several systems showed an upward bias for one particular sample of at least 25%. Weighted linear regression showed overall bias ranging from -8% to 32% for E(2) and from 7% to 41% for progesterone. CONCLUSIONS: Few automated methods succeed in having an excellent reproducibility for E(2) and progesterone. Given the high bias values it is suggested that, for performance testing, results be compared whenever possible with a reference method. The linear relationship as assessed by comparing results with those obtained by ID-GC/MS using samples from different donors was not assured for most methods.
Asunto(s)
Química Clínica/normas , Estradiol/sangre , Inmunoensayo/normas , Progesterona/sangre , Control de Calidad , Bélgica , Femenino , Secciones por Congelación , Cromatografía de Gases y Espectrometría de Masas , Humanos , Modelos Lineales , Embarazo , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: Pharmacological doses of estrogens or testosterone are used to limit the final height of girls or boys with constitutional tall stature but the mechanism behind this growth inhibition is still debated. We therefore studied the changes in the circulating components of the insulin-like growth factor (IGF) system during high dose sex steroid therapy. DESIGN AND METHODS: Twenty three girls and twenty boys with constitutional tall stature were treated with 100 microg ethinylestradiol per day or 250 mg testosterone ester every 14 days respectively. In 19 girls and 18 boys, the levels of IGF-I, free IGF-I, IGF-II, acid-labile subunit (ALS) and IGF binding proteins (IGFBP)-2 to -6 were measured before and 3-6 months after the start of therapy (group 1). In 18 girls and 11 boys, samples were collected at the end of therapy and 3 to 6 months afterwards (group 2). Fourteen girls and nine boys belonged to both groups. All parameters were measured by radioimmunoassay or ELISA. RESULTS: Levels of IGF-I were decreased significantly by estrogen treatment but remained unchanged during testosterone treatment. Free IGF-I decreased during estrogen treatment but increased during testosterone therapy. Estrogens increased IGF-II and testosterone reduced it. The important reduction of IGFBP-2 during estrogen therapy is not reproduced by androgen therapy, neither is the stimulation by estrogens of IGFBP-4. IGFBP-3 is not modulated by either sex steroid. We found that IGFBP-6 is up-regulated by testosterone but not by estrogens; the reverse is true for ALS, which increased during estrogen treatment but remained unchanged during testosterone treatment. CONCLUSIONS: Our findings demonstrate that androgens and estrogens exert differential effects on the circulating levels of several IGF components.
Asunto(s)
Estatura , Etinilestradiol/administración & dosificación , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor II del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/análisis , Testosterona/administración & dosificación , Adolescente , Proteínas Portadoras/sangre , Femenino , Glicoproteínas/sangre , Humanos , 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 , Proteína 4 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , MasculinoRESUMEN
OBJECTIVE: Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia. RESEARCH DESIGN AND METHODS: Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA(+) and 62 PCA(-), aged 45 +/- 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies. RESULTS: PCA(+) patients had higher gastrin (P < 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA(-) subjects. ECL cell hyper/dysplasia was present in seven PCA(+) patients who showed higher CgA levels (P < 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (beta = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA(+) patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor. CONCLUSIONS: PCA(+) patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.
Asunto(s)
Biomarcadores de Tumor/sangre , Cromograninas/sangre , Diabetes Mellitus Tipo 1/sangre , Células Enterocromafines/fisiología , Ácido Hidroxiindolacético/sangre , Tumores Neuroendocrinos/sangre , Autoanticuerpos/sangre , Cromogranina A , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Células Enterocromafines/patología , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Humanos , Hiperplasia , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/sangreRESUMEN
OBJECTIVE: To investigate the effect of high-dose oestrogen treatment on IGF-I, IGF-II, free-dissociable IGF-I and the IGF-binding proteins (IGFBP)-2 to -6 in girls with constitutional tall stature. METHODS: In patient cohort 1, blood samples were drawn before and after 3 months of daily oral treatment with 0.1 mg ethinyloestradiol. In cohort 2, samples were collected at the end of the treatment period and 3 to 6 months afterwards. IGFs and IGFBPs were analysed by specific immunoassays and by Western ligand blot. RESULTS: Total IGF-I decreased significantly on oestrogen treatment and increased again after oestrogen withdrawal. Ligand blot analysis showed a clear reduction in a 34 kDa band, corresponding to IGFBP-2, and a strong induction of a 24 kDa band, corresponding to the non-glycosylated form of IGFBP-4. These changes were confirmed by specific immunological methods. The serum levels of IGFBP-3, IGFBP-5 and IGFBP-6 remained unchanged during the first 3 months of treatment. In cohort 2, IGFBP-3 and IGFBP-6 increased after oestrogen withdrawal. Free-dissociable IGF-I fell to 35+/-4% during oestrogen therapy and rose again when the treatment was stopped. CONCLUSIONS: Oestrogens modulate the serum concentrations of several components of the IGF system. The fall in total IGF-I is not explained by a decrease in IGFBPs but probably results from a decreased synthesis.