Determination of reference intervals for serum magnesium

AbstractBiochemical measurements in “special fluids” are complicated with the problem of reference intervals. Reference intervals are difficult to establish for these types of samples since they are usually only collected in patients with clinical suspicion of disease. Determination of neurotransmitter metabolites in cerebrospinal fluid illustrates this difficulty. This paper will review the factors and circumstances that have been identified or are suspected to modifythe concentration of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid. In addition to obvious parameters such as age-related variation that can affect the concentration of 5-HIAA and HVA in cerebrospinal fluid, a varietyof other factors can explain the wide range of “control” group sizes reported in the literature. Reference intervals must take into account the purpose of cerebrospinal fluid examinations, whether they be prospective studies to explore physio-pathologic relationships or for diagnostic purposes. In the latter case, certain neurological disorders cannot be excluded if a single measured value is within the reference interval.

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Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2011.776 ◽

2012 ◽

Vol 50 (5) ◽

Author(s):

Hallvard Lilleng ◽

Stein Harald Johnsen ◽

Tom Wilsgaard ◽

Svein Ivar Bekkelund

Keyword(s):

Creatine Kinase ◽

General Population ◽

Reference Interval ◽

Reference Intervals ◽

Control Analysis ◽

Age Group ◽

Background Population ◽

Norwegian Population ◽

Reference Limits ◽

Laboratory Reference

AbstractLaboratory reference intervals are not necessarily reflecting the range in the background population. This study compared creatine kinase (CK) reference intervals calculated from a large sample from a Norwegian population with those elaborated by the Nordic Reference Interval Project (NORIP). It also assessed the pattern of CK-normalization after standardized control analyses.New upper reference limits (URL) CK values were calculated after exclusion of individuals with risk of hyperCKemia and including individuals with incidentally detected hyperCKemia after they had completed a standardized control analysis. After exclusion of 5924 individuals with possible causes of hyperCKemia, CK samples were analyzed in 6904 individuals participating in the 6th survey of The Tromsø Study. URL was defined as the 97.5 percentile.New URL in women was 207 U/L. In men <50 years it was 395 U/L and in men ≥50 years 340 U/L. In individuals with elevated CK, normalization grade after control analysis was inversely correlated to the CK level (p<0.04).URL CK values in women and in men <50 years of age were in accordance with URL CK values given by the NORIP. In men ≥50 years, a higher URL was found and the findings suggest an upward adjustment of URL in this age group.

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Experience with the Urinary Tetrasaccharide Metabolite for Pompe Disease in the Diagnostic Laboratory

Metabolites ◽

10.3390/metabo11070446 ◽

2021 ◽

Vol 11 (7) ◽

pp. 446

Author(s):

Jennifer T. Saville ◽

Maria Fuller

Keyword(s):

Pompe Disease ◽

Late Onset ◽

Reference Interval ◽

Laboratory Diagnosis ◽

Reference Intervals ◽

Confirmatory Test ◽

Diagnostic Laboratory ◽

Age Related ◽

Initial Drop ◽

Monitoring Treatment

Following clinical indications, the laboratory diagnosis of the inherited metabolic myopathy, Pompe disease (PD), typically begins with demonstrating a reduction in acid alpha-glucosidase (GAA), the enzyme required for lysosomal glycogen degradation. Although simple in concept, a major challenge is defining reference intervals, as even carriers can have reduced GAA, and pseudodeficiencies complicate interpretation. Here, we developed a mass spectrometric assay for quantification of a urinary glycogen metabolite (tetrasaccharide) and reported on its utility as a confirmatory test for PD in a diagnostic laboratory. Using two age-related reference intervals, eight returned tetrasaccharide concentrations above the calculated reference interval but did not have PD, highlighting non-specificity. However, retrospective analysis revealed elevated tetrasaccharide in seven infantile-onset (IOPD) cases and sixteen late-onset (LOPD) cases, and normal concentrations in one heterozygote. Prospective tetrasaccharide analysis in nine individuals with reduced GAA confirmed IOPD in one, LOPD in six and identified two heterozygotes. Using this metabolite as a biomarker of therapeutic response was not overly informative; although most patients showed an initial drop following therapy initiation, tetrasaccharide concentrations fluctuated considerably and remained above reference intervals in all patients. While useful as a confirmation of PD, its utility as a biomarker for monitoring treatment warrants further investigation.

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Impact of age, body weight and metabolic risk factors on steroid reference intervals in men

Acta Endocrinologica ◽

10.1530/eje-19-0928 ◽

2020 ◽

Vol 182 (5) ◽

pp. 459-471

Author(s):

Marco Mezzullo ◽

Guido Di Dalmazi ◽

Alessia Fazzini ◽

Margherita Baccini ◽

Andrea Repaci ◽

...

Keyword(s):

Risk Factors ◽

Reference Intervals ◽

Metabolic Risk Factors ◽

Specific Reference ◽

Metabolic Risk ◽

Cross Sectional ◽

Cholesterol Ratio ◽

Age Related ◽

Reference Limits ◽

17 Hydroxyprogesterone

Objective To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men. Design Cross-sectional study. Methods Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation. Thirteen steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts. Results We observed lower steroid precursors and testosterone and increase in estrone levels in men with higher BMI ranges. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, DHEA, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29 nmol/L lower (P = 0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (−0.34 nmol/L, P = 0.045), cortisol (−87 nmol/L, P = 0.045–0.002) and corticosterone (−10.1 nmol/L, P = 0.048–0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively. Conclusions Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.

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Determination of high sensitive cardiac troponin I 99th percentile upper reference limits in a healthy Pakistani population

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.36.6.2328 ◽

2020 ◽

Vol 36 (6) ◽

Author(s):

Kulsoom Bahadur ◽

Aamir Ijaz ◽

Momin Salahuddin ◽

Aftab Alam

Keyword(s):

Cardiac Troponin ◽

Troponin I ◽

Laboratory Data ◽

Cardiac Troponin I ◽

Medical Institute ◽

Pakistani Population ◽

Reference Limits ◽

Males And Females ◽

Gender Specific

Objective: This study aims to establish the 99th percentile upper reference limits of high sensitive cardiac troponin I in a healthy Pakistani population. Methods: It was an Observational cohort study carried out in Department of Chemical Pathology and Endocrinology Rehman Medical Institute Peshawar, over the period of one year (January 2019- December 2019). Total 299 cardio-healthy males and females were interviewed and taken past medical history. Based on history, clinical examination, echocardiogram and laboratory data including results of estimated glomerular filtration rate (eGFR) and N-terminal pro-B-type natriureteric peptide (NT-proBNP), subjects with possible subclinical diseases were excluded. High Sensitive Cardiac Troponin I (hs-cTtrop I) was analysed on Abbot ARCHITECT STAT ci8200 using chemiluminescent immunoassay technique. The 99th percentile upper reference limit (URL) of hs-cTtrop I was determined using a non-parametric statistic, while gender specific results were compared. Results: In this study, 178 males (59.5%) and 121 females (40.5%) were included. The median Interquartile ranges (IQR) of age was 57 (11.6) for males and 56 (13) for females. The 99th percentile URL hs-cTtrop I was found to be 33.9 ng/L, while gender specific values were 38.41ng/L and 15.73ng/L for males and females, respectively (p= 0.0045). Conclusion: High sensitivity cardiac troponin I 99th percentile URL in our study population was found to be 33.9 ng/L with gender specific values being 38.41 ng/L and 15.73ng/L for males and females respectively. Troponin I in males was substantially high in comparison with females. doi: https://doi.org/10.12669/pjms.36.6.2328 How to cite this:Bahadur K, Ijaz A, Salahuddin M, Alam A. Determination of high sensitive cardiac troponin I 99th percentile upper reference limits in a healthy Pakistani population. Pak J Med Sci. 2020;36(6):---------. doi: https://doi.org/10.12669/pjms.36.6.2328 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Establishment of variation source and age-related reference interval models for 22 common biochemical analytes in older people using real-world big data mining

Age and Ageing ◽

10.1093/ageing/afaa096 ◽

2020 ◽

Vol 49 (6) ◽

pp. 1062-1070

Author(s):

Chaochao Ma ◽

Liangyu Xia ◽

Xinqi Chen ◽

Jie Wu ◽

Yicong Yin ◽

...

Keyword(s):

Big Data ◽

Older People ◽

Real World ◽

Reference Interval ◽

Reference Intervals ◽

Ageing Population ◽

Factors Affecting ◽

Age Related ◽

The Status ◽

Source Models

Abstract Background the ageing population has increased in many countries, including China. However, reference intervals (RIs) for older people are rarely established because of difficulties in selecting reference individuals. Here, we aimed to analyse the factors affecting biochemical analytes and establish RI and age-related RI models for biochemical analytes through mining real-world big data. Methods data for 97,220 individuals downloaded from electronic health records were included. Three derived databases were established. The first database included 97,220 individuals and was used to build age-related RI models after identifying outliers by the Tukey method. The second database consisted of older people and was used to establish variation source models and RIs for biochemical analytes. Differences between older and younger people were compared using the third database. Results sex was the main source of variation of biochemical analytes for older people in the variation source models. The distributions of creatinine and uric acid were significantly different in the RIs of biochemical analytes for older people established according to sex. Age-related RI models for biochemical analytes that were most affected by age were built and visualized, revealing various patterns of changes from the younger to older people. Conclusion the study analysed the factors affecting biochemical analytes in older people. Moreover, RI and age-related RI models of biochemical analytes for older people were established to provide important insight into biological processes and to assist clinical use of various biochemical analytes to monitor the status of various diseases for older people.

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SUN-222 Pre- and Post-Pubertal Reference Ranges for Oxygenated Androgens in Saliva

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.629 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Joanne Adaway ◽

Graeme Eisenhofer ◽

Angela Huebner ◽

Nils Krone ◽

Malcolm McTaggart ◽

...

Keyword(s):

Reference Interval ◽

Reference Intervals ◽

Range Data ◽

Reference Ranges ◽

Non Invasive ◽

Premature Adrenarche ◽

Upper Limits ◽

Males And Females ◽

Monitoring Treatment ◽

Ovarian Syndrome

Abstract Oxygenated androgens such as 11 β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) contribute significantly to the androgen pool in humans and their measurement has been shown to be useful in diagnosing disorders such as polycystic ovarian syndrome or premature adrenarche and also in monitoring treatment of congenital adrenal hyperplasia, alongside the classical androgens. Their measurement in saliva is particularly advantageous due to the non-invasive nature of sampling, meaning samples can easily be taken regularly to monitor treatment; however reference range data is not currently available for 11OHA4 and 11KT, limiting their clinical use. These analytes were measured in saliva samples from pre and post-pubertal males and females to inform reference ranges for these analytes. Samples collected into salivettes as part of the PRIMMS study (Technische Universität Dresden) were used for this work. A total of 130 samples (35 from pre-pubertal females, 43 from post-pubertal females, 42 from pre-pubertal males and 20 from post-pubertal males) were analysed for 11OHA4 and 11KT by LC-MS/MS. The ages of the participants ranged from 3.77 to 14.0 years in the pre-pubertal samples and 13.9-17.9 years in the post-pubertal samples. Pubertal status was determined clinically. The upper cut-off of the reference interval for 11OHA4 was 560 pmol/L in pre-pubertal females and 590 pmol/L in males, whilst 11KT had an upper limit of 216 pmol/L in females and 205 pmol/L in males. The upper limits of the ranges were higher in post-pubertal samples, with ranges of up to 1542 pmol/L in females and 1775 pmol/L in males for 11OHA4; the ranges for 11KT were up to 654 pmol/L for post pubertal females and 585 pmol/L for post-pubertal males. The data shows, as expected, a rise in the 11 oxygenated androgens post puberty. The upper limits of reference intervals for both analytes were very similar in males and females both pre- and post pubertally. These data can be used to inform clinical interpretation of the 11-oxygenated androgens; further work is required with larger cohorts of samples to develop more robust reference ranges.

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Reference intervals for 21 clinical chemistry analytes in arterial and venous umbilical cord blood

Clinical Chemistry ◽

10.1093/clinchem/39.6.1041 ◽

1993 ◽

Vol 39 (6) ◽

pp. 1041-1044 ◽

Cited By ~ 16

Author(s):

S L Perkins ◽

J F Livesey ◽

J Belcher

Keyword(s):

Alkaline Phosphatase ◽

Umbilical Cord ◽

Clinical Chemistry ◽

Venous Blood ◽

Reference Interval ◽

Reference Intervals ◽

Nonparametric Analysis ◽

Term Infants ◽

Male And Female ◽

Gamma Glutamyltransferase

Abstract Reference intervals were determined for 21 clinical chemistry analytes in umbilical cord arterial and venous blood from healthy term infants. Nonparametric analysis (rank number) was used to determine the central 95% reference interval. No significant differences were observed between male and female infants. Reference intervals for glucose, urea, creatinine, urate, phosphate, calcium, albumin, total protein, cholesterol, triglycerides, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, gamma-glutamyltransferase, and magnesium all were significantly different from adult values.

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Reference intervals for thyreotropin and thyroid hormones for healthy adults based on the NOBIDA material and determined using a Modular E170®

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2008.258 ◽

2008 ◽

Vol 46 (9) ◽

Cited By ~ 5

Author(s):

Lennart Friis-Hansen ◽

Linda Hilsted

Keyword(s):

Thyroid Hormones ◽

Reference Interval ◽

Reference Intervals ◽

Healthy Adults ◽

Free Triiodothyronine ◽

Thyroglobulin Antibodies ◽

Men And Women ◽

Blood Samples ◽

Upper Limit

Abstract: The aim of the present study was to establish Nordic reference intervals for thyreotropin (TSH) and the thyroid hormones in heparinized plasma.: We used 489 heparinized blood samples, collected in the morning, from the Nordic NOBIDA reference material, from healthy adults without medication. TSH, thyroxine, free thyroxine, triiodothyronine, free triiodothyronine, and thyroglobulin antibodies (Tg-ab) were measured using assays for Roche Modular E170: The measured concentrations for the thyroid hormones, but not TSH, followed a Gaussian distribution. There were more TPO-ab and Tg-ab positive women than men. After exclusion of the TPO-ab and the Tg-ab positive individuals, the reference interval TSH was 0.64 (0.61–0.72) to 4.7 (4.4–5.0) mIU/L. The exclusion of these ab-positive samples also minimized the differences in TSH concentrations between the sexes and the different Nordic countries. For the thyroid hormones, there were only minor differences between the reference intervals between the Nordic populations and between men and women. These reference intervals were unaffected by removal of the TPO-ab and TG-ab positive samples.: The upper limit of the TSH reference interval in our study is high compared to some other recent reports. This could be due to blood sampling in the morning. Furthermore, the Roche platform gives slightly higher results than other platforms. The number and distribution of the samples in the NOBIDA material makes it suitable for the determination of hormone Nordic reference intervals.Clin Chem Lab Med 2008;46:1305–12.

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Partitioning biochemical reference data intosubgroups: comparison of existing methods

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2004.123 ◽

2004 ◽

Vol 42 (7) ◽

Cited By ~ 14

Author(s):

Ari Lahti

Keyword(s):

Reference Data ◽

Reference Interval ◽

Reference Intervals ◽

New Method ◽

Poor Correlation ◽

Specific Reference ◽

Common Reference ◽

Reference Limits ◽

The Common ◽

The Ideal

AbstractFour existing methods for partitioning biochemical reference data into subgroups are compared. Two of these, the method of Sinton et al. and that of Ichihara and Kawai, are based on a quotient of a difference between the subgroups and the reference interval for the combined distribution. The criterion of Sinton et al. appears rather stringent and could lead to recommendations to apply a common reference interval in many cases where establishment of group-specific reference intervals would be more useful. The method of Ichihara and Kawai is similar to that of Sinton et al., but their criterion, based on a quantity derived from between-group and within-group variances, seems to lead to inconsistent results when applied to some model cases. These two methods have the common weakness of using gross differences between subgroup distributions as an indicator of differences between their reference limits, while distributions with different means can actually have equal reference limits and those with equal means can have different reference limits. The idea of Harris and Boyd to require that the proportions of the subgroup distributions outside the common reference limits be kept reasonably close to the ideal value of 2.5% as a prerequisite for using common reference limits seems to have been a major improvement. The other two methods considered, that of Harris and Boyd and the “new method” follow this idea. The partitioning criteria of Harris and Boyd have previously been shown to provide a poor correlation to those proportions, however, and the weaknesses of their method are summarized in a list of five drawbacks. Different versions of the new method offer improvements to these drawbacks.

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