Prevalence of thyroid dysfunction and autoimmunity in the older population and implications of age-specific reference ranges.

OBJECTIVE: To investigate the prevalence of thyroid dysfunction and autoimmunity (TAI) and to determine age-specific reference ranges in individuals <60 and ≥60-year-old. Furthermore we investigated the impact of the age-specific reference ranges on the prevalence of thyroid dysfunction. DESIGN: Retrospective analysis of laboratory data collected over six months in 2015, mainly from individuals consulting the outpatient clinic. METHOD: Data from 676 individuals were withheld, after having applied strict exclusion criteria to avoid confounders. After exclusion of individuals with TAI (TPO-abs >60kIU/L) and/or outliers, data of 547 individuals were used to determine age-specific reference ranges. The prevalence of subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (sch) was determined according to the reference ranges from the commercial assay and also according to the calculated age-specific reference ranges. From our study population. RESULTS: From the 676 individuals included, 559 (83%) were <60year-old and 117 (17%) ≥60year-old. The prevalence of sch and TAI was comparable between both groups (8.6% vs. 13.7% and 15.4% vs. 20.5% respectively). The prevalence of SCH was significantly higher in individuals ≥60years, compared to that in individuals <60years (14.5% vs. 5.4%; p<0.001). The calculated 2.5 and 97.5 percentile for the age-specific TSH range was 0.24 and 4.4 mIU/L in individuals <60years and 0.15 and 8.2mIU/L in individuals ≥60years. When these the prevalence of sch and SCH was then determined on the basis of the age-specific reference ranges, the prevalence of SCH significantly decreased in individuals ≥60years (14.5% to 5%; p=0.027) and it then became comparable with that in individuals <60years (5% vs. 3%). CONCLUSIONS: The prevalence of SCH was higher in individuals ≥60years, compared to that in individuals <60years, but when age-specific TSH reference ranges were used, it was comparable between both study groups. In order to avoid misclassification in older individuals, it is important to use age-specific reference ranges in daily clinical practice.

Thrombin generation in children with sickle cell disease: relationship with age, hemolysis, transcranial Doppler velocity, and hydroxyurea treatment.

INTRODUCTION: Increased thrombin generation (TG) was described in sickle cell disease (SCD) children. The aim of this study was to characterize TG at the individual level and assess its relationship with age, hemolysis, transcranial Doppler velocity (TCD), and hydroxyurea treatment. PATIENTS AND METHODS: TG was triggered in the platelet-poor plasma using tissue factor and phospholipids with addition of thrombomodulin in 97 SCD at steady state and 80 control children. Patients and controls were aged from 2 to 20 years, and they were distributed in four categories of age: [2-5], [6-10], [11-15], and [16-20] years. For each subject, ratio of endogenous thrombin potential (rETP) and peak height (rPeak) was calculated as subject's value divided by the mean value of controls of the same age range. rETP and rPeak of patients were considered abnormal when > mean + 2SD of controls. LDH, total hemoglobin, and reticulocyte count were measured as markers of hemolysis. Data on hydroxyurea treatment and TCD were collected from medical records. RESULTS: Overall, 38.1% and 44.3% of patients showed elevated rETP and rPeak, respectively. rETP and rPeak decreased significantly with increasing age. In homozygous (SS) patients, TCD velocities and all markers of hemolysis correlated significantly with both rETp and rPeak. Negative correlations were observed between these ratios and the duration of hydroxyurea treatment. CONCLUSION: Elevated TG in SCD children is mainly related to younger age and to the intensity of hemolysis. There probably a link between TG and cerebral vasculopathy in these patients. Hydroxyurea may have a beneficial effect, which could be related to the duration of treatment.

Assessment of the diagnostic performances of IgA heavy and light chain pairs in patients with IgA monoclonal gammopathy.

OBJECTIVES: Preliminary results of the IgA Hevylite™ assay including the establishment of the 95% reference interval and assessment of the specificity and sensitivity in different populations are reported. DESIGN AND METHODS: The concentrations of IgA heavy and light chains (HLC) enabling to determine an IgAκ/IgAλ ratio were quantified in 119 apparently healthy individuals to generate 95% reference intervals. The specificity of this assay was assessed in 48 patients with an isolated polyclonal IgA increase. In a retrospective analysis of 68 patients with a monoclonal component type IgA (MC-IgA) identified by serum immunofixation (IFE), IgA HLC ratio values were compared with known results for serum protein electrophoresis (SPE) and free light chain (FLC) ratios. RESULTS: The 95% reference range obtained in 119 controls (0.91-2.04) was close to that quoted by the manufacturer (0.80-2.04). Eight of the 48 patients (16.7%) with a polyclonal IgA increase had an IgA HLC ratio above the upper limit of the 95% reference interval. The IgA HLC ratio identified 65 (95.6%) among 68 patients with MC-IgA identified on the basis of IFE. For 34 of these patients (50%), MC-IgA was not detected by SPE due to its co-migration with alpha-2 or beta-globulins. CONCLUSIONS: Compared with serum IFE, the IgA HLC ratio has a sensitivity of 95.6%. Further studies are needed to assess the specificity of the IgA HLC ratio in patients with an isolated polyclonal increase of serum IgA.

Influence of bedside blood insulin measurement on acute coronary syndrome pathways.

BACKGROUND: The aim of the study was to evaluate the influence of blood insulin measurements on acute coronary syndrome (ACS) pathways. METHODS: All patients admitted to the emergency department within 12 months for acute, retrosternal, constrictive chest pain lasting for more than 30 minutes; cardiogenic pulmonary edema; electrocardiogram ST changes; and echographic alterations were included. The study parameters were clinical (age, sex, blood pressure, presence of pulmonary rales and gallop), including classic laboratory tests associated with troponin T, blood insulin levels, and hemoglobin A1C, and echographic values. These were taken on admission and throughout hospital stay. All patients underwent a coronary angiography for ACS diagnosis confirmation as well as treatment intention. RESULTS: Sixty patients were included in the study. Abnormal blood insulin levels were present on admission in 47% of the population. Blood insulin level was significantly correlated to thrombolysis in myocardial infarction coronary perfusion score (Spearman Rank, 0.55, P < 0.0001). Abnormal insulinemia was normalized with reperfusion. Insulin was administered essentially to the 16 patients with hypoinsulinemia. Patients with hypoinsulinemia seem to have the most severe coronary lesions and highest Killip score. CONCLUSIONS: In ACS, insulin levels are altered in half of the patients. After the investigators noted its tight correlation with the thrombolysis in myocardial infarction coronary flow score, its determination could be important in ACS for triggering emergency coronary angiography for percutaneous coronary intervention. This could modify the critical pathways of ACS patients in the emergency department.

False positive carbohydrate-deficient transferrin results in chronic hemodialysis patients related to the analytical methodology.

OBJECTIVES: Chronic kidney disease stage V is associated with a metabolic acidosis, a disturbance also observed in heavy alcohol consumption. Carbohydrate-deficient transferrin is considered the most accurate biomarker for identifying chronic alcohol abuse. We tested whether increased CDT results occurred in patients on dialysis therapy. DESIGN AND METHODS: One hundred twenty-two samples from HD patients were analyzed by three different analytical methods and the results were compared with those obtained in 48 healthy volunteers. RESULTS: On the basis of the upper 97.5th percentile, positive CDT results were found in 25.4%, 9.8% and 12.3% of the HD patients with particle-enhanced immunonephelometry, capillary electrophoresis and HPLC, respectively. A significant correlation between CDT values and transferrin concentration was found for the particle-enhanced immunonephelometric test (r: -0.311; p: 0.0009). CONCLUSIONS: A high rate of positive CDT results was observed in HD patients with the particle-enhanced immunonephelometry and seems to be related to the low transferrin concentration.

[Biological variation of glycation and mean blood glucose have greater influence on Hba1c levels in type 1 young diabetic patients than glucose instability]. / La variation biologique de la glycation et la moyenne glycémique ont une plus grande influence sur l'HbA1c des jeunes diabétiques de type 1 que l'instabilité glycémique.

The aim of the study was to assess the relative influence of mean blood glucose (MBG), glucose instability (GI) and biological variation of glycohemoglobin (BVG) on HbA1c. The study included 378 unselected young type 1 diabetic patients with a diabetes duration > 1 year. There were 1,409 visits with simultaneous HbA1c determinations and self-monitoring of BG meter downloads. GI was quantified by measuring the standard deviation (SD) of the recorded BG values. A statistical model was developed to predict HbA1c from MBG. Hemoglobin glycation index (HGI) was calculated (HGI = observed HbA1c--predicted HbA1c) for each visit to assess BVG based on the directional deviation of observed HbA1c from that predicted by MBG in the model. Afterwards, the population was divided by thirds into high-, moderate-, and low-HGI groups, i.e. high-, moderate-, and low-glycators, reflecting BVG. A total of 246,000 preprandial BG measurements were analysed, with a mean of 177 per visit. Grand MBG +/- SD was 171 +/- 40 mg/dl. Predicted HbA1c was calculated from the equation: 3.8399 + 0.0242 x MBG (r = 0.66; p < 0.0001). A MBG change of 40 mg/dl corresponded to 1% change in HbA1c, within the range 6-12%. Multiple regression analysis showed no significant relationship between SD and HbA1c, after adjustment for MBG. MBG was 10 times more important than SD to predict HbA1c. MBG was not statistically different between the high- and low glycators, but HbA1c was significantly different. Multiple linear regression was used to predict HbA1c from MBG, SD and BVG (measured by HGI), adjusted for age, duration, gender and ethnic origin. BVG and MBG had large influences on HbA1c, the impact of BVG being 84% of the impact of MBG. On the other hand, GI had only 17% of the impact of MBG. In conclusion the effect of BVG on HbA1c is independent and much greater that the influence attributable to GI. Hemoglobin glycation phenotype, responsible for BVG, may be important for the clinical assessment of diabetic patients in order to avoid complications.

Plasma osteoprotegerin is an independent risk factor for mortality and an early biomarker of coronary vascular calcification in chronic kidney disease.

BACKGROUND: Cardiovascular disease is the major cause of morbidity and mortality in chronic kidney disease (CKD) and early biomarkers are required which can predict disease and death in such patients. The aim of our study was to investigate if osteoprotegerin (OPG) could be a predictor of coronary artery calcification (CAC) and mortality in CKD. METHODS: A total of 77 outpatients (32 with pre-dialysis CKD and 45 undergoing hemodialysis) were followed-up during 2 years. Measurements of CAC were performed using Siemens Multidetector CT software and calcium scores were measured according to the Agatston method. RESULTS: OPG was an independent predictor of the Agatston score for CAC and correlated with the degree of CAC in pre-dialysis patients. A two-sample t-test characterized survivors as having a better glomerular filtration rate, lower Agatston scores, and lower serum levels of OPG. Kaplan-Meier survival curves separated survivors from non-survivors at plasma OPG cut-off levels of <3.1 ng/mL. A multivariable logistic regression analysis showed that OPG was an independent predictor of mortality from all causes in CKD patients. CONCLUSIONS: OPG predicted mortality in CKD patients and could be a valuable biomarker in early detection of CAC in these patients.

Comparison of high-performance liquid chromatography with fluorescence detection versus enzymatic assay to measure blood pyruvate in clinical practice.

OBJECTIVES: Measurement of blood pyruvate allows the diagnosis of patients with mitochondrial disorders. The aim of this study was to assess the analytical performance of an HPLC and an enzymatic assay for quantifying pyruvate. METHODS: The criteria of analytical performance for each assay and the correlation between methods were evaluated. RESULTS: Both assays were linear over the range 0 to 500 micromol/L of pyruvate. The total precision of the HPLC and enzymatic method were <5% for pyruvate concentrations ranging from 28 and 213 micromol/L and 42 and 181 micromol/L, respectively. The limit of detection for the HPLC technique was determined to be 1 micromol/L and the limit of quantification was 5 micromol/L. The mean recovery for HPLC was 99%. Results for the enzymatic assay showed a limit of detection of 5 micromol/L and a limit of quantification of 10 micromol/L. The mean recovery was 90.4%. In the method comparison, the HPLC method gave values that were on average 24 micromol/L higher than the enzymatic assay. CONCLUSION: Both techniques demonstrated good analytical performance. The negative bias observed for the enzymatic assay can be explained by its lesser good recovery compared to the HPLC assay.

Immunonephelometric quantification of specific urinary proteins versus a simple electrophoretic method for characterizing proteinuria.

OBJECTIVES: The quantification of urinary proteins presenting different molecular sizes is useful in characterizing a proteinuria. We assessed the performance of an electrophoretic system, the Hydragel Urine Profile, which allows firstly the identification of proteinuria and secondly a qualitative detection of monoclonal free light chains (FLC). DESIGN AND METHODS: Initially, the proteinuria was characterized on 127 pathological urines by quantifying albumin, a1microglobulin, immunoglobulins G by immunonephelometric quantification technique and the results were compared with the protein pattern obtained by the electrophoretic method. Secondly, we assessed the sensitivity and specificity of this electrophoretic test for the detection and characterization of Bence Jones proteins. FLC were analyzed quantitatively by an immunonephelometric assay and qualitatively by the electrophoretic test in 150 urines. RESULTS: The agreement between the two methods was good with a percentage of homology for characterizing the proteinuria of 89%. For detecting a monoclonal FLC, the electrophoretic method demonstrated a lesser sensitivity but a higher specificity compared to the immunoassay. CONCLUSION: The Urine Profile kit is a reliable assay that can be used as a screening test to differentiate the type of proteinuria.

Assessment of the analytical performance and the sensitivity of serum free light chains immunoassay in patients with monoclonal gammopathy.

OBJECTIVES: A new immunoassay which quantifies Kappa, Lambda free light chains (FLC) and a ratio of Kappa to Lambda FLC has been reported to be sensitive for detecting a variety of FLC diseases. We assessed the analytical criteria and the diagnostic performance of this immunoassay in patients who present a monoclonal gammopathy. DESIGN AND METHODS: Quantification of FLC, serum protein electrophoresis (SPE) and immunofixation (IFE) were performed on patients who present a monoclonal gammopathy of undetermined significance (MGUS), an intact immunoglobulin multiple myeloma (IIMM) or a light chain multiple myeloma (LCMM). RESULTS: The monoclonal component was identified by IFE in the sera of all patients. Based on the diagnostic reference range, the ratio of Kappa to Lambda FLC was abnormal in 25% of the tested population, compared to 94% for SPE in MGUS patients. For IIMM and LCMM, the FLC ratio was abnormal in 70% and 100% of the population, compared to 85% and 40% for SPE, respectively. CONCLUSION: SPE and IFE have a higher sensitivity for identifying MGUS and IIMM.