Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

Preliminary evaluation of eight less frequent endocrine assays designed for MAGLUMI 800 chemiluminescence immunoanalyzer.

Transition to new analytical systems and methods requires end-user verification to ensure acceptability for routine use. Our aim was to verify precision of MAGLUMI 800 immunoassay analyzer for 17-hydroxyprogesterone (17-OHP), 25-hydroxy vitamin D (25(OH)D), aldosterone, androstenedione, growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3) and renin, as well as to assess their comparability with the routinely used assays. Precision was evaluated at two levels following the CLSI EP15-A2 protocol. Method comparison included parallel analysis of 40 routine samples for each assay on MAGLUMI 800 and the routinely used automated or manual immunoassays. Within-run coefficients of variation (CV) ranged from 0.8% (androstenedione) to 14.5% (aldosterone), between-run CVs from 1.0% (IGFBP-3) to 12.8% (renin), while within-laboratory (total) precision CVs were from 2.1% (IGFBP-3) to 14.9% (renin). All assays with the exception of IGF-1 and 25(OH)D at the low concentration control level, satisfied biological variation criteria for imprecision. Passing-Bablok regression showed proportional difference for 17-OHP and aldosterone, constant for androstenedione, while both constant and proportional difference was revealed for 25(OH)D, GH and IGF-1. Statistically significant relative biases higher than the desirable biological variation acceptance criteria were observed for 17-OHP, 25(OH)D, aldosterone, androstenedione and IGF-1. The evaluated assays need further assessment as well as verification of reference intervals in order to be suitable for introduction into routine practice in our laboratory. Our study clearly demonstrates that we are still far from achieving immunoassay standardization and comparability of results.

Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with ß-thalassemia major.

BACKGROUND: Disturbances of glucose metabolism are common in ß-thalassemia major (ß-TM). AIM: This study was conducted to assess the pattern of glucose homeostasis in pediatric ß-TM patients comparing oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS). METHODS: Two-hundred ß-TM patients were studied and those with random blood glucose (RBG) ≥7.8 mmol/L (140 mg/dL) were subjected to OGTT, insertion of CGMS and measurement of fasting C peptide, fasting insulin, and hemoglobin A1c (HbA1c). RESULTS: Twenty patients (10%) had RBG ≥ 7.8 mmol/L. Using OGTT, 6 out of 20 patients (30%) had impaired glucose tolerance (IGT) while 7 (35%) patients were in the diabetic range. CGMS showed that 7/20 (35%) patients had IGT and 13 (65%) patients had diabetes mellitus (DM); 10 of the latter group had HbA1c readings within diabetic range. The percentage of diabetic patients diagnosed by CGMS was significantly higher than that with OGTT (P = 0.012). Serum ferritin was the only independent variable related to elevated RBG. All ß-TM patients with DM were non-compliant to chelation therapy. CONCLUSIONS: The use of CGMS in the diagnosis of early glycemic abnormalities among pediatric patients with ß-TM appears to be superior to other known diagnostic modalities.

Comparing associations of different metabolic syndrome definitions with ischemic stroke in Chinese elderly population.

OBJECTIVES: Studies have showed the associations between different definitions of metabolic syndrome (MetS) and risk of ischemic stroke were inconsistent. In this study, we compared associations of different MetS definitions with ischemic stroke in Chinese elderly population. METHODS: A total of 1713 individuals aged 70-84years from Rugao Longevity and Ageing Study were analyzed. The MetS was defined by four different criteria: Chinese Adult Dyslipidemia Prevention Guide, International Diabetes Federation (IDF), Updated ATPIII (Updated ATPIII) by American heart association/American heart, lung and blood institute (AHA/NHLBI), and Joint Interim Statement(JIS) recommended by IDF and the American heart association/American national institutes of health/American heart, lung and blood institute (AHA/NIH/NHLBI). RESULTS: Prevalence of MetS in the whole population was 24.0% (Chinese guide), 32.5% (IDF), 38.8% (Updated ATPIII) and 24.0% (JIS) and in stroke population was 27.1% (Chinese guide), 41.1% (IDF), 48.8% (Updated ATPIII) and 27.1% (JIS), respectively. The agreement between definitions was highest in Updated ATPIII vs. IDF (kappa=0.863). It showed that only definitions of IDF (OR 1.55, 95%CI 1.04-2.31, p=0.031) and Updated ATPIII (OR 1.64, 95%CI 1.11-2.42, p=0.013) were independently associated with risk of ischemic stroke in multivariable logistic regression analysis. The risk of ischemic stroke increased with the increasing of numbers of Mets components in Updated ATPIII (p<0.05). CONCLUSION: In this population, Updated ATPIII criteria was a more suitable definition of Mets than definitions of Chinese guide, IDF and JIS for screening high-risk individuals of ischemic stroke, and the additive effects of Mets components might play a greater role than its composition alone in ischemic stroke.

Modelling, verification, and calibration of a photoacoustics based continuous non-invasive blood glucose monitoring system.

This paper examines the use of photoacoustic spectroscopy (PAS) at an excitation wavelength of 905 nm for making continuous non-invasive blood glucose measurements. The theoretical background of the measurement technique is verified through simulation. An apparatus is fabricated for performing photoacoustic measurements in vitro on glucose solutions and in vivo on human subjects. The amplitude of the photoacoustic signals measured from glucose solutions is observed to increase with the solution concentration, while photoacoustic amplitude obtained from in vivo measurements follows the blood glucose concentration of the subjects, indicating a direct proportionality between the two quantities. A linear calibration method is applied separately on measurements obtained from each individual in order to estimate the blood glucose concentration. The estimated glucose values are compared to reference glucose concentrations measured using a standard glucose meter. A plot of 196 measurement pairs taken over 30 normal subjects on a Clarke error grid gives a point distribution of 82.65% and 17.35% over zones A and B of the grid with a mean absolute relative deviation (MARD) of 11.78% and a mean absolute difference (MAD) of 15.27 mg/dl (0.85 mmol/l). The results obtained are better than or comparable to those obtained using photoacoustic spectroscopy based methods or other non-invasive measurement techniques available. The accuracy levels obtained are also comparable to commercially available continuous glucose monitoring systems.

[A new immunoassay for estradiol on the Advia-Centaur (Siemens) system: analytical and clinical performances]. / Performances analytiques d'un nouveau dosage de l'estradiol pour l'Advia-Centaur (Siemens) : évaluation clinique dans le cadre de l'assistance médicale à la procréation.

The objective of this study is to present results for measurement of estradiol (E(2)) in serum and control materials with a new automated assay (eE(2)) that could be used in random continuous access mode on the Siemens laboratories Advia-Centaur immunoassay analyzer. We evaluated the imprecision (within and between run), the linearity, the limit of detection, and the functional sensitivity. We have tested the assay for monitoring ovulation stimulation for in vitro fertilization and embryo transfer (IVF-ET) throughout the most frequent protocol utilized in our IVF centre (n = 247). Results are compared to those obtained by the E(2)6 assay, one other assay on the Advia-Centaur immunoassay analyzer (Siemens), routinely used in our hormonology department. The obtained results show that the new assay presents better analytical performances (precision, linearity, limits of detection and sensibility) than the previous technique.

Salivary cortisol as a diagnostic tool for Cushing's syndrome and adrenal insufficiency: improved screening by an automatic immunoassay.

BACKGROUND: Salivary cortisol is increasingly used to assess patients with suspected hypo- and hypercortisolism. This study established disease-specific reference ranges for an automated electrochemiluminescence immunoassay (ECLIA). METHODS: Unstimulated saliva from 62 patients with hypothalamic-pituitary disease was collected at 0800 h. A peak serum cortisol level below 500 nmol/l during the insulin tolerance test (ITT) was used to identify hypocortisolism. Receiver-operating characteristic (ROC) analysis allowed establishment of lower and upper cutoffs with at least 95% specificity for adrenal insufficiency and adrenal sufficiency. Saliva from 40 patients with confirmed hypercortisolism, 45 patients with various adrenal masses, and 115 healthy subjects was sampled at 2300 h and after low-dose dexamethasone suppression at 0800 h . ROC analysis was used to calculate thresholds with at least 95% sensitivity for hypercortisolism. Salivary cortisol was measured with an automated ECLIA. RESULTS: When screening for secondary adrenal insufficiency, a lower cutoff of 3.2 nmol/l and an upper cutoff of 13.2 nmol/l for unstimulated salivary cortisol allowed a highly specific diagnosis (i.e. similar to the ITT result) in 26% of patients. For identification of hypercortisolism, cutoffs of 6.1 nmol/l (sensitivity 95%, specificity 91%, area under the curve (AUC) 0.97) and 2.0 nmol/l (sensitivity 97%, specificity 86%, AUC 0.97) were established for salivary cortisol at 2300 h and for dexamethasone-suppressed salivary cortisol at 0800 h. CONCLUSIONS: The newly established thresholds facilitated initial screening for secondary adrenal insufficiency and allowed excellent identification of hypercortisolism. Measurement by an automated immunoassay will allow broader use of salivary cortisol as a diagnostic tool.

[Inventory of the use of natriuretic peptides in France]. / État des lieux de l'utilisation des peptides natriurétiques en France.

Since the introduction of routine assay for natriuretic peptides (NP), there is an increasing number of clinical applications for these assays. Due to the continuously increasing number of prescription of those tests, a reappraisal of the use of natriuretic peptide assays, namely BNP and NT-proBNP in France was necessary. This was achieved through a national survey to obtain a detailed description of NP prescription and realization by French laboratories. A questionnaire was sent in April 2010 to hospital and private clinical chemists. Statistical analysis of results concerned 584 answers. This survey demonstrated an equivalent use of BNP and NT-proBNP both in public or private laboratories together with a huge heterogeneity of tests used within labs. Medical prescription heterogeneity both in public or private sectors confirms the large implication of those tests in clinical diagnosis. These assays are not yet standardized, so clinicians and biologists should be very careful when interpreting the results for diagnostic or therapeutic monitoring.

The design and development of fluorescent nano-optodes for in vivo glucose monitoring.

BACKGROUND: The advent of fluorescent nanosensors has enabled intracellular monitoring of several physiological analytes, which was previously not possible with molecular dyes or other invasive techniques. We have extended the capability of these sensors to include the detection of small molecules with the development of glucose-sensitive nano-optodes. Herein, we discuss the design and development of glucose-sensitive nano-optodes, which have been proven functional both in vitro and in vivo. METHODS: Throughout the design process, each of the sensor formulations was evaluated based on their response to changes in glucose levels. The percent change in signal, sensor reversibility, and the overall fluorescence intensity were the specific parameters used to assess each formulation. RESULTS: A hydrophobic boronic acid was selected that yielded a fully reversible fluorescence response to glucose in accordance with the sensor mechanism. The change in fluorescence signal in response to glucose was approximately 11%. The use of different additives or chromophores did not improve the response; however, modifications to the plasticized polymeric membrane extended sensor lifetime. CONCLUSIONS: Sensors were developed that yielded a dynamic response to glucose and through further modification of the components, sensor lifetime was improved. By following specific design criteria for the macrosensors, the sensors were miniaturized into nano-optodes that track changes in glucose levels in vivo.

Comparison in the performance of glucose meters in blood glucose monitoring during pregnancy.

AIMS: To compare the performance of the four latest models of glucose meters in capillary blood glucose monitoring during pregnancy. METHODS: 208 pregnant women with gestational diabetes were recruited. Each subject had simultaneous capillary glucose monitoring by two study glucose meters and venous plasma glucose assay. The performance of four glucose meters was compared using error grid analysis (EGA) and the agreement between the meter readings and plasma glucose by Bland-Altman plot analysis. RESULTS: Elite, Advantage II and CareSens had more than 90% of readings in the acceptable target range of EGA. CareSens had the lowest mean bias by Bland-Altman analysis while Advantage II had the highest proportion of readings within 5% difference from plasma glucose. Readings from all glucose meters except Optium were not influenced by the change in maternal hematocrit levels. CONCLUSIONS: The performance of four study glucose meters appeared very similar.

Use of the site of subcutaneous insulin administration for the measurement of glucose in patients with type 1 diabetes.

OBJECTIVE To simplify and improve the treatment of patients with type 1 diabetes, we ascertained whether the site of subcutaneous insulin infusion can be used for the measurement of glucose. RESEARCH DESIGN AND METHODS Three special indwelling catheters (24-gauge microperfusion [MP] catheters) were inserted into the subcutaneous adipose tissue of subjects with type 1 diabetes (n = 10; all C-peptide negative). One MP catheter was perfused with short-acting insulin (100 units/ml, Aspart) and used for insulin delivery and simultaneous glucose sampling during an overnight fast and after ingestion of a standard glucose load (75 g). As controls, the further two MP catheters were perfused with an insulin-free solution (5% mannitol) and used for glucose sampling only. Plasma glucose was measured frequently at the bedside. RESULTS Insulin delivery with the MP catheter was adequate to achieve and maintain normoglycemia during fasting and after glucose ingestion. Tissue glucose concentrations derived with the insulin-perfused catheter agreed well with plasma glucose levels. Median correlation coefficient and median absolute relative difference values were found to be 0.93 (interquartile range 0.91-0.97) and 10.9%, respectively. Error grid analysis indicated that the percentage number of tissue values falling in the clinically acceptable range is 99.6%. Comparable analysis results were obtained for the two mannitol-perfused catheters. CONCLUSIONS Our data suggest that estimation of plasma glucose concentrations from the glucose levels directly observed at the site of subcutaneous insulin infusion is feasible and its quality is comparable to that of estimating plasma glucose concentrations from glucose levels measured in insulin-unexposed subcutaneous tissue.

Utilizing Ecological Momentary Assessment in pediatric obesity to quantify behavior, emotion, and sleep.

This study examined the feasibility of using Ecological Momentary Assessment (EMA) to examine important domains relevant to interregulatory health processes in overweight adolescent females in their natural environments. Participants were 20 overweight adolescent females engaged in a cognitive-behavioral and motivational interviewing intervention aimed at weight loss and improving mood (11-19 years old, 80% white, 15% African American, mean BMI = 39). During this EMA protocol, participants were asked to report their physical activity (PA), nutrition, mood, and sleep during 14 cellular phone calls over three extended weekends (Thursday to Monday). Simultaneously, participants wore an actigraph (armband and watch communicator) that provided instantaneous PA feedback (steps taken and kilocalories) and sleep parameters (duration and efficiency). EMA compliance rates for the armband and phone calls were 74.7 +/- 0.3% and 64.2 +/- 0.3%, respectively. Data from the armband and phone calls are presented to illustrate the depth of information acquired by utilizing this innovative methodology.

Capillary blood glucose screening (Accu-Chek Advantage) for gestational diabetes.

OBJECTIVE: To determine optimal threshold of capillary blood glucose screening (Accu-Chek Advantage) for gestational diabetes. STUDY DESIGN: A cross-sectional analytical study. MATERIAL AND METHOD: Capillary and venous blood of pregnant women who attended the antenatal clinic at Trang Regional Hospital between August 2007 and May 2008 were collected for glucose testing (by approach of American Diabetes Association's Fourth International Workshop-Conference on Gestational Diabetes) at one hour after taking 50 gm glucose. The glucose values of Accu-Check Advantage were compared with the standard venous plasma glucose. The receiver operator characteristic (ROC) curve was created to determine the optimal threshold of the capillary blood test screening for gestational diabetes. RESULTS: A total of 816 pregnant women were enrolled in the present study. Their capillary blood glucose values and plasma glucose values were checked with the Accu-Chek Advantage and the central laboratory chemistry analyzer respectively. The good correlation between capillary blood glucose and plasma glucose values was found (correlation coefficient = 0.80, 95% CI 0.77-0.82). There was a significant difference in the average values of capillary blood and plasma blood (134.1 vs. 122.7 mg/dl, respectively). When the data were analyzed by ROC curve, the optimal level of capillary blood by Accu-Chek Advantage for performing a 100 gm oral glucose tolerance test was 140 mg/dl (reference plasma glucose level of at least 140 mg/dl). The sensitivity specificity likelihood ratio for a positive test result and likelihood ratio for a negative test result were 93.8%, 83.6%, 5.71 and 0.07, respectively. The potential advantages of capillary blood glucose screening are simple to use, cheap and convenient. CONCLUSION: Accu-Chek Advantage is suitable for screening gestational diabetes using the optimal threshold capillary glucose level of 140 mg/dl.

Accuracy of bedside glucometry in critically ill patients: influence of clinical characteristics and perfusion index.

OBJECTIVES: To determine the accuracy of bedside glucose strip assay on capillary blood and on whole blood and to identify factors predictive of discrepancies with the laboratory method. PATIENTS AND METHODS: We conducted a prospective 3-month (July 1-September 30, 2003) study in 85 consecutive patients who required blood glucose monitoring. Values obtained with a glucose test strip on capillary blood and on whole blood were compared with those obtained in the laboratory during serial blood sampling (up to 4 samples per patient). The test strip values were considered to disagree significantly with the laboratory values when the difference exceeded 20%. Clinical and biological parameters and the perfusion index, based on percutaneous oxygen saturation monitoring, were recorded when each sample was obtained. RESULTS: Capillary glucose values conflicted with laboratory reference values in 15% of samples. A low perfusion index was predictive of conflicting values (P=.04). Seven percent of values obtained with glucose strip on whole-blood samples conflicted with laboratory reference values; factors associated with these discrepancies were mean arterial hypotension (P=.007) and generalized mottling (P=.04). CONCLUSION: Bedside blood glucose values must be interpreted with care in critically ill patients. A low perfusion index, reflecting peripheral hypoperfusion, is associated with poor glucose strip performance. Bedside measurements in whole blood seem to be most reliable, except in patients with arterial hypotension and generalized mottling.

Indirect estimation of pediatric Health Related Limits for serum thyrotropin using the ADVIA Centaur analyzer.

OBJECTIVES: To determine pediatric reference values for thyrotropin using Advia Centaur analyzer. DESIGN AND METHODS: The study was conducted in a large regional hospital on TSH results obtained from 5741 females and 4332 males aged 0-17 years. After the exclusion of the results outside 4 standard deviations, we calculated the Health Related Limits (HRLs) following the indirect Kairisto's procedure and using the software GraphROC. RESULTS: The lower HRL of TSH concentration was 0.70 mU/L in the years 0-11 and 0.50 mU/L in the following years. The upper TSH HRL was 6.9 mU/L in males vs. 5.7 mU/L in females in the first year and 6.7 mU/L vs. 5.3 in the period 1-2 years. The upper HRLs in females and males were similar in the following years and the upper HRL in the 13-17 years class was 3.8 mU/L. CONCLUSIONS: The indirect methods appear reliable for calculating the pediatric HRLs for TSH.

[Development of a new noninvasive blood sugar detector].

The level of blood sugar is an improtant indicator used in the diagnosis and management of diabetes mellitus. In this respect, polarimeter and blood sugar detector were conventionally and generally used in hospitals; However, the former one is already obsolete; the latter one is invasive. In this paper, the development of a novel noninvasive blood-sugar detector is described. The experiment indicate that this detector is nonivasive, safe, fast, and easy to operate, and it can be of wide application.