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

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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EXPRESS: Method dependent variation in TSH and FT4 reference intervals in pregnancy: a systematic review

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/00045632211026955 ◽

2021 ◽

pp. 000456322110269

Author(s):

O E Okosieme ◽

Medha Agrawal ◽

Danyal Usman ◽

Carol Evans

Keyword(s):

Systematic Review ◽

Reference Interval ◽

First Trimester ◽

Reference Intervals ◽

Assay Method ◽

Specific Reference ◽

Upper Limits ◽

Wide Range ◽

Assay Methods ◽

In Pregnancy

Background: Gestational TSH and FT4 reference intervals may differ according to assay method but the extent of variation is unclear and has not been systematically evaluated. We conducted a systematic review of published studies on TSH and FT4 reference intervals in pregnancy. Our aim was to quantify method-related differences in gestation reference intervals, across four commonly used assay methods, Abbott, Beckman, Roche, and Siemens. Methods: We searched the literature for relevant studies, published between January 2000 and December 2020, in healthy pregnant women without thyroid antibodies or disease. For each study, we extracted trimester-specific reference intervals (2.5â97.5 percentiles) for TSH and FT4 as well as the manufacturer provided reference interval for the corresponding non-pregnant population. Results: TSH reference intervals showed a wide range of study-to-study differences with upper limits ranging from 2.33 to 8.30 mU/L. FT4 lower limits ranged from 4.40â13.93 pmol/L, with consistently lower reference intervals observed with the Beckman method. Differences between non-pregnant and first trimester reference intervals were highly variable, and for most studies the TSH upper limit in the first trimester could not be predicted or extrapolated from non-pregnant values. Conclusions: Our study confirms significant intra and inter-method disparities in gestational thyroid hormone reference intervals. The relationship between pregnant and non-pregnant values is inconsistent and does not support the existing practice in some laboratories of extrapolating gestation references from non-pregnant values. Laboratories should invest in deriving method-specific gestation reference intervals for their population.

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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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DETERMINING REFERENCE RANGES FOR TREC AND KREC ASSAYS IN IMMUNE DEFICIENCY SCREENING OF NEWBORNS IN RUSSIAN FEDERATION

Medical Immunology (Russia) ◽

10.15789/1563-0625-2019-3-527-538 ◽

2019 ◽

Vol 21 (3) ◽

pp. 527-538

Author(s):

M. A. Gordukova ◽

I. A. Korsunsky ◽

Yu. V. Chursinova ◽

M. M. Byakhova ◽

I. P. Oscorbin ◽

...

Keyword(s):

Reference Interval ◽

Reference Population ◽

Dried Blood Spots ◽

Reference Intervals ◽

Asymmetric Distribution ◽

Reference Ranges ◽

Individual Values ◽

Experimental Values ◽

Deficiency Screening ◽

Guthrie Cards

In this work, we used a reference population of newborns and sampled dried blood spots on Guthrie cards of 2,739 individual samples to determine the reference intervals for TRECs and KRECs values, in order to diagnose primary immunodeficiency by means of neonatal screening. The median absolute values for TRECs and KRECs were 195 (CI95%: 185-206) and 185 (CI95%: 176-197) copies per μl, respectively; the normalized value for TRECs was 2780 (CI95%: 2690-2840), and for KRECs, 2790 (CI95%: 2700-2900) copies per 2 × 105 copies of the albumin gene or 105 cells. The reference interval was calculated for 99 and 99.9 percentiles of total TRECs and KRECs individual values. Due to asymmetric distribution of data, the outliers were filtered off, using the Tukey’s criterion applied after logarithmic transformation of the data. When analyzing absolute values for TREC/KREC (per μL of blood), no “drop-down” TRECs values were identified; for KRECs, 18 experimental values were excluded from further analysis (from 9.8 to 13.5). The outlying values were not identified among the normalized values of TRECs/KRECs. The obtained reference values for TRECs and KRECs (at the 0.1 percentile level) were, respectively, 458 and 32 per 105 cells, or 23 and 17 per μl of blood samples from neonates.

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First- and Second-Trimester Reference Intervals for Thyroid Hormones during Pregnancy in “Rhea” Mother-Child Cohort, Crete, Greece

Journal of Thyroid Research ◽

10.4061/2011/490783 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 16

Author(s):

Polyxeni Karakosta ◽

Leda Chatzi ◽

Emmanouil Bagkeris ◽

Vasiliki Daraki ◽

Dimitris Alegakis ◽

...

Keyword(s):

Thyroid Hormones ◽

Reference Interval ◽

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Specific Reference ◽

Reference Ranges ◽

Thyroid Function Tests ◽

Second Trimester ◽

Free Triiodothyronine ◽

Reference Limit

Estimation and interpretation of thyroid function tests in pregnant women is of utmost importance for maternal, fetal and neonatal health. Our objective was to calculate laboratory- and geography-specific reference intervals for thyroid hormones during pregnancy in an iodine-sufficient area of the Mediterranean, Crete, Greece. This project was performed in the context of “Rhea” mother-child cohort. Fulfillment of extensive questionnaires and estimation of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and antithyroid antibodies were performed. The reference population was defined using inclusion criteria regarding thyroidal, obstetric, and general medical status of women. Reference interval for TSH was 0.05–2.53 μIU/mL for the first and 0.18–2.73 μIU/mL for the second trimester. 6,8% and 5,9% of women in the first and second trimester, respectively, had TSH higher than the upper reference limit. These trimester-specific population-based reference ranges are essential in everyday clinical practice for the correct interpretation of thyroid hormone values and accurate classification of thyroid disorders.

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Reference ranges for clinical electrophysiology of vision

Documenta Ophthalmologica ◽

10.1007/s10633-021-09831-1 ◽

2021 ◽

Author(s):

C. Quentin Davis ◽

Ruth Hamilton

Keyword(s):

Reference Values ◽

False Negative ◽

Reference Interval ◽

Reference Intervals ◽

Clinical Electrophysiology ◽

Reference Ranges ◽

Physiological Measurement ◽

Negative Results ◽

Reference Limits ◽

Suitable Reference

Abstract Introduction Establishing robust reference intervals for clinical procedures has received much attention from international clinical laboratories, with approved guidelines. Physiological measurement laboratories have given this topic less attention; however, most of the principles are transferable. Methods Herein, we summarise those principles and expand them to cover bilateral measurements and one-tailed reference intervals, which are common issues for those interpreting clinical visual electrophysiology tests such as electroretinograms (ERGs), visual evoked potentials (VEPs) and electrooculograms (EOGs). Results The gold standard process of establishing and defining reference intervals, which are adequately reliable, entails collecting data from a minimum of 120 suitable reference individuals for each partition (e.g. sex, age) and defining limits with nonparametric methods. Parametric techniques may be used under some conditions. A brief outline of methods for defining reference limits from patient data (indirect sampling) is given. Reference intervals established elsewhere, or with older protocols, can be transferred or verified with as few as 40 and 20 suitable reference individuals, respectively. Consideration is given to small numbers of reference subjects, interpretation of serial measurements using subject-based reference values, multidimensional reference regions and age-dependent reference values. Bilateral measurements, despite their correlation, can be used to improve reference intervals although additional care is required in computing the confidence in the reference interval or the reference interval itself when bilateral measurements are only available from some of subjects. Discussion Good quality reference limits minimise false-positive and false-negative results, thereby maximising the clinical utility and patient benefit. Quality indicators include using appropriately sized reference datasets with appropriate numerical handling for reporting; using subject-based reference limits where appropriate; and limiting tests for each patient to only those which are clinically indicated, independent and highly discriminating.

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Reference Intervals for Potassium, Sodium and Chloride among Libyan Healthy People

International Journal of Diabetes & Metabolic Disorders ◽

10.33140/ijdmd.05.03.05 ◽

2020 ◽

Vol 5 (3) ◽

Keyword(s):

Population Based ◽

Reference Intervals ◽

Healthy People ◽

Sodium Potassium ◽

Direct Potentiometry ◽

Percentile Method ◽

Upper Limits ◽

Males And Females ◽

Blood Specimens ◽

Lower Limits

Background: In Libya, all laboratories use reference intervals (RIs) derived from other country’s populations, which differ from Libyan population in many aspects such as daily habits and race. Due to these differences, it is assumed that those RIs are not applicable to Libyans. Aim: The aim of this study was to establish RIs of sodium, potassium and chloride in serum of Libyan people. Materials and Methods: Two hundred and fifty-seven blood specimens of healthy people (males and females) were collected using venipuncture untreated tubes. The specimens were centrifuged for 15 minutes and the obtained sera were analyzed for their content of sodium, potassium and chloride using direct potentiometry method. Results and Discussion: The non-parametric percentile method was applied to establish the RIs of sodium, chloride and potassium, which were found to be: 135-143.3; 103-110; 3.7-5.2 mmol/L, respectively. There were no considerable differences in lower limits and/or upper limits of all established RIs between males and females, except that the upper limit of Cl− for females was slightly higher than that for males. Conclusion: As there are evident regional differences in RIs, the established RIs in this study will be more favorable in Libya than those listed in the manufacturer’s kit or those adopted from other population-based references.

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Determination of reference intervals for serum magnesium

Clinical Chemistry ◽

10.1093/clinchem/36.5.756 ◽

1990 ◽

Vol 36 (5) ◽

pp. 756-758 ◽

Cited By ~ 8

Author(s):

G O Duncanson ◽

H G Worth

Keyword(s):

Alkaline Phosphatase ◽

Gaussian Distribution ◽

Parametric Analysis ◽

Serum Magnesium ◽

Reference Interval ◽

Reference Intervals ◽

Age Related ◽

Reference Limits ◽

Males And Females

Abstract Using a discrete analyzer and a dye-binding method, we measured magnesium in 800 patients' samples received for routine analysis. By excluding data from samples for which the calcium and (or) alkaline phosphatase values were outside defined reference limits, we established a reference interval for magnesium. Because the data showed a gaussian distribution, we could use parametric analysis to establish age-related intervals for both males and females.

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Use of laboratory information system data for indirect estimation of reference interval for vitamin B12

LaboratoriumsMedizin ◽

10.1515/labmed-2015-0045 ◽

2015 ◽

Vol 39 (6) ◽

Author(s):

Mufide Oncel ◽

Emel Sahin ◽

Aysel Kiyici ◽

Bahattin Adam

Keyword(s):

Information System ◽

Vitamin B12 ◽

Clinical Laboratory ◽

Reference Interval ◽

Serum Levels ◽

Reference Intervals ◽

National Committee ◽

Reference Ranges ◽

Laboratory Information System ◽

The One

AbstractIn common, clinical laboratories use reference intervals recommended by the manufacturers. Various factors affect laboratory tests such as age, sex, diet and genetics. So, it is recommended for each laboratory to determine its own reference ranges for each test used. We aimed to establish our reference interval for vitamin B12.The data archive of laboratory information system was searched for a 1-year period between January and December, 2013. Among 2526 subjects searched for vitamin B12, 2368 remained (1–70 years old, 512 male and 1856 female) when we excluded the outliers for estimation of reference range for vitamin B12 with nonparametric method according to National Committee for Clinical Laboratory Standards (NCCLS) C28-A3 guidelines. Serum levels of vitamin B12 were determined with electrochemiluminescent technique.New reference interval for vitamin B12 derived from our results was 101–702 pg/mL, and was not affected by gender.New reference interval was different from the one recommended by the manufacturer. We suggest that established reference interval reflects our population better than the values recommended by the manufacturer.

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Regional adjustment of thyroid hormone reference intervals

LaboratoriumsMedizin ◽

10.1515/labmed-2014-0008 ◽

2014 ◽

Vol 38 (5) ◽

Author(s):

Mira Ganslmeier ◽

Claudia Castrop ◽

Klemens Scheidhauer ◽

Ina-Christine Rondak ◽

Peter B. Luppa

Keyword(s):

Reference Values ◽

Reference Interval ◽

Population Based ◽

Reference Intervals ◽

Clinical Findings ◽

Reference Ranges ◽

History Of ◽

Study Population ◽

Roche Diagnostics

AbstractWe conducted a study in a metropolitan area to establish regional reference intervals for thyreotropin (TSH) and the thyroid hormones free triiodthyronine (fT3) and free thyroxine (fT4). This was due to the different reference ranges, based on varying regional trials, presented for a widely used electrochemiluminescence immunoassay system.We investigated 292 apparently healthy adult subjects and excluded those with known history of thyroid disease, abnormal findings in the ultrasonographic examination of the thyroid gland, or elevated thyroid autoantibodies in serum. Accordingly, 204 of 292 subjects were included as the reference collective. We measured serum concentrations of TSH, fT3, and fT4 using the Elecsys assays from Roche Diagnostics and calculated the 2.5th and 97.5th percentiles.The nonparametrically calculated reference values for TSH and fT4 were 0.58–3.49 mIU/L and 11.58–20.46 pmol/L, respectively. Statistically remarkable is the finding of a normal Gaussian distribution of the fT3 serum concentration, leading to the parametric reference interval of 3.56–5.88 pmol/L.The established reference values for this regional collective showed tighter intervals than the reference ranges provided by the manufacturer. A carefully selected study population, based on the correspondent National Academy of Clinical Biochemistry criteria, ensured a valid set of reference ranges for TSH, fT3, and fT4, providing a basis for accurate in vitro thyroid testing. The 2.5th percentile for the fT3 is now in better accordance with clinical findings.

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Adult Reference Ranges for Serum Cystatin C, Creatinine and Predicted Creatinine Clearance

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456320003700101 ◽

2000 ◽

Vol 37 (1) ◽

pp. 49-59

Author(s):

Hazel Finney ◽

David J Newman ◽

Christopher P Price

Keyword(s):

Serum Creatinine ◽

Creatinine Clearance ◽

Cystatin C ◽

Blood Donors ◽

Reference Range ◽

Reference Interval ◽

Reference Intervals ◽

Reference Ranges ◽

Serum Cystatin C ◽

Serum Cystatin

Serum cystatin C measurement has been previously shown by ourselves and others to be a better indicator of changes in glomerular filtration rate (GFR) than serum creatinine. However, the available literature on reference values for cystatin C concentration remains surprisingly sparse; we thus set out to determine an adult reference range. Blood was taken from 309 healthy blood donors and creatinine and cystatin C concentrations were measured using commercially available automated methodologies. In addition, predicted creatinine clearances were calculated using the Cockcroft and Gault formula. The 95% reference intervals for creatinine, predicted creatinine clearance and cystatin C for all blood donors, regardless of gender, were 68–118 μmol/L, 58–120 ml/min/1·73 m2 and 0·51–0·98 mg/L, respectively. For women, the intervals were 68–98 μmol/L, 60–119 ml/min/1·73 m2 and 0·49–0·94 mg/L; for men, they were 78–123 μmol/L, 57–122 ml/min/1·73 m2 and 0·56–0·98 mg/L. The mean 95% reference interval for cystatin C in all donors under 50 years of age was 0·53–0·92 mg/L; for those over 50 years of age it was 0·58–1·02 mg/L. The small difference between male and female ranges meant that a single reference range for cystatin C could be established for all adults under 50 years of age without adjustment for body surface area. Serum cystatin C measurement offers a simpler and more sensitive screening test than serum creatinine for early changes in GFR.

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