Intra- and interindividual biological variation of five analytes used in assessing thyroid function: implications for necessary standards of performance and the interpretation of results.

1986 ◽  
Vol 32 (6) ◽  
pp. 962-966 ◽  
Author(s):  
M C Browning ◽  
R P Ford ◽  
S J Callaghan ◽  
C G Fraser
Keyword(s):  
Reference Range ◽  
Population Based ◽  
Biological Variation ◽  
Reference Ranges ◽  
Hormone Concentration ◽  
Free Triiodothyronine ◽  
Mean Values ◽  
Optimal Patient Care ◽  
Total Triiodothyronine ◽  
The Mean

Abstract Intra- and interindividual components of biological variation have been determined for total thyroxin (TT4), free thyroxin (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyrotropin (TSH). Calculated analytical goals (CV, %) for the precision required for optimal patient care are: TT4 less than or equal to 2.5, FT4 less than or equal to 4.7, TT3 less than or equal to 5.2, FT3 less than or equal to 3.9, and TSH less than or equal to 8.1. The marked degree of individuality demonstrated for all hormones indicates that, if conventional population-based reference ranges are used uncritically, major changes in hormone concentration may not be correctly identified for some patients because observed values continue to lie within the reference range. At analyte concentrations approximating the mean values found in this study, and for analytical performance meeting the appropriate analytical goal, the differences required for consecutive results to be significantly different (p less than or equal to 0.5) have been calculated as: TT4, 14.7 nmol/L; FT4, 5.7 pmol/L; TT3, 0.6 nmol/L; FT3, 1.3 pmol/L, and TSH, 0.7 milli-int. unit/L.

Intra-individual variation of thyroxin, triiodothyronine, and thyrotropin in treated hypothyroid patients: implications for monitoring replacement therapy.

1988 ◽  
Vol 34 (4) ◽  
pp. 696-699 ◽  
Author(s):  
M C Browning ◽  
W M Bennet ◽  
A J Kirkaldy ◽  
R T Jung
Keyword(s):  
Primary Hypothyroidism ◽  
Free Triiodothyronine ◽  
Post Dose ◽  
Strict Adherence ◽  
Mean Values ◽  
Specimen Collection ◽  
Total Triiodothyronine ◽  
The Mean ◽  
Random Fluctuations ◽  
Hypothyroid Patients

Abstract We measured total thyroxin (TT4), free thyroxin (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyrotropin (TSH) in serum sampled before and 1, 2, 4, 6, and 8 h after administration of prescribed doses of thyroxin to 12 patients with proven primary hypothyroidism. At 2, 4, and 6 h post-dose, the mean values for TT4 and FT4 and also that at 8 h for FT4 significantly (P less than 0.05) exceeded the corresponding pre-dose values. No significant changes were found for TT3, FT3, or TSH. The mean intra-individual CVs over the study period were TT4 4.9%, FT4 5.7%, TT3 8.7%, FT3 8.7%, and TSH 20.2%. Individual subjects showed small but predictable changes in TT4 and FT4. Changes in TT3 and FT3 were greater but random. Fluctuations in TSH were greatest, but in all subjects with detectable concentrations the variations were of similar magnitude. We conclude that strict adherence to timing of specimen collection in relation to dosage is probably unnecessary.

scholarly journals Reference Ranges and Determinants of Thyroid Function During Early Pregnancy: The SELMA Study

2018 ◽  
Vol 103 (9) ◽  
pp. 3548-3556 ◽  
Author(s):  
Arash Derakhshan ◽  
Huan Shu ◽  
Maarten A C Broeren ◽  
Ralph A de Poortere ◽  
Sverre Wikström ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Population Based ◽  
Reference Ranges ◽  
Free Triiodothyronine ◽  
Free T4 ◽  
Serum Cotinine ◽  
Child Asthma ◽  
Mother And Child ◽  
Total Triiodothyronine ◽  
Main Determinants

Abstract Context Establishing reference ranges as well as identifying and quantifying the determinants of thyroid function during pregnancy is important for proper clinical interpretation and optimizing research efforts. However, such data are sparse, specifically for triiodothyronine measurements, and most studies do not take into account thyroid antibodies or human chorionic gonadotropin. Objective To determine reference ranges and to identify/quantify determinants of TSH, free T4 (FT4), free triiodothyronine (FT3), total T4 (TT4), and total triiodothyronine (TT3). Design, Setting, and Participants This study included 2314 participants of the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study, a population-based prospective pregnancy cohort of mother-child pairs. Reference ranges were calculated by 2.5th to 97.5th percentiles after excluding thyroperoxidase antibody (TPOAb)–positive and/or thyroglobulin antibody (TgAb)–positive women. Intervention None. Main Outcome Measures TSH, FT4, FT3, TT4, and TT3 in prenatal serum. Results After exclusion of TPOAb-positive women, reference ranges were as follows: TSH, 0.11 to 3.48 mU/L; FT4, 11.6 to 19.4 pmol/L; FT3, 3.72 to 5.92 pg/mL; TT4, 82.4 to 166.2 pmol/L; and TT3, 1.28 to 2.92 nmol/L. Additional exclusion of TgAb-positive women did not change the reference ranges substantially. Exposure to tobacco smoke, as assessed by questionnaires and serum cotinine, was associated with lower TSH and higher FT3 and TT3. Body mass index (BMI) and gestational age were the main determinants of TSH (only for BMI), FT4, FT3, TT4, and TT3. Conclusions We show that the exclusion of TgAb-positive women on top of excluding TPOAb-positive women hardly affects clinical reference ranges. We identified various relevant clinical determinants of TSH, FT4, FT3, TT4, and TT3 that could reflect endocrine-disrupting effects and/or effects on thyroid hormone transport or deiodination.

Can ETP Be Used As a Clinical Assay in a Clinically Laboratory Setting

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2304-2304
Author(s):  
Mayra Telesca ◽  
De-Hui Ku ◽  
Priti Patel ◽  
Yale S. Arkel ◽  
Nehal Patel
Keyword(s):  
Reference Range ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Reference Ranges ◽  
Normal Reference Range ◽  
Mean Values ◽  
Clinical Assay ◽  
Normal Reference ◽  
The Mean

Abstract Abstract 2304 We initiated a study to look at the consistency of the data using the thrombinoscope/Diagnostica Stago- Calibrated Automated Thrombogram™ (CAT) system. The CAT is a thrombin generation method described previously by Hemker. The goal of this phase of the study was to determine whether this test can be used as a clinical assay. First, we tried to determine the stability of the sample along with the normal reference range of the assay. For this, we collected samples from 20 normal healthy subjects to determine the stability of the sample and the normal reference range. The collected samples were tested at 0, 1 and 2 hours after collection. These samples had been kept at room temperature throughout the testing. Part of the aliquot samples were frozen at −80°C, and then the frozen sample tubes were thawed and analyzed at 2, 3, 4, and 8 weeks. The ETP determined in the 0, 1, and 2 hours after collection revealed no statistical significance in the mean values. This would indicate that a delay in starting the testing procedure in the freshly collected specimens up to 2 hours does not statistically affect the results. This would tend to indicate that blood samples drawn in the physician's office or satellite labs distally located from the core hospital labs may be suitable for testing if the specimen could be brought to the testing laboratory within 2 hours after the specimen has been centrifuged. The plasma aliquot specimens that were frozen for 2, 3, 4, and 8 weeks were then thawed and run as described for the 0 hour plasma sample. The 2 and 3 week specimens had statistically significant higher mean values compared to the mean values of the 0 hour mean value. However the 4 and 8 week values were not statistically different from the 0 hour run specimen. From these observations it appears that the process of freezing over the 2–3 week period, had an increased potential to form thrombin, but the longer freezing period of 4 to 8 weeks the data revealed no statistical difference from the 0 hour mean values. Secondly, we tried to see if the reference ranges are different between the different populations. We have used the 4 week frozen sample ETP as our normal reference range (2149.3 nM/min +/− 455.2) in order to compare with other populations. For this, we performed the ETP from sample collected from patient with either factor V Leiden or prothrombin G20210A mutations, with a total of 15 patients included. The mean ETP was 2663.4 nM/min +/− 605, which was statistically different from the normal population (P<0.01). We also tried to see if the ETP from a lupus inhibitor (LI) patient is different from the normal reference range, with a total of 55 LI positive patients included. The mean ETP was 2284.6 nM/min +/− 539.8, which was not statistically significantly different from the normal reference range. We also tried to determine the therapeutic range for the ETP in a patient on warfarin therapy. The patients in the study were LI negative, and neither the factor V Leiden nor the prothrombin G20210A mutations were detected. We grouped these patients into three categories: INR 1.3 to 1.9 (N=15), INR20–3.0(N=21) and INR>3.0 (N=8). The ETP values for these three groups were 1229.7 nM/min +/− 237.5, 916.6 nM/min +/−256.8 and 558.7 nM/min +/− 212.6. Based on our data, we postulated that the ETP between 650 – 1200 nM/min fall in the 2.0 – 3.0 INR range, which is the generally accepted therapeutic range. In conclusion, the data indicate that the ETP assay can be used as a clinical assay. However, there is a need to establish the reference range for each of the patient populations under investigation. So far we only determined reference ranges for the LI patients and patients with inherited hypercoagulable disorders. We hope to establish the reference ranges for other subpopulations, such as pregnant women and hemophiliacs in the future. Disclosures: No relevant conflicts of interest to declare.

Effects of Age and Health on the Euthyroid Reference Ranges for Serum Free Thyroxine and Free Triiodothyronine

1985 ◽  
Vol 24 (02) ◽  
pp. 57-65 ◽  
Author(s):  
J. E. M. Midgley ◽  
K. R. Gruner
Keyword(s):  
Lower Limit ◽  
Healthy Subjects ◽  
Thyroid Dysfunction ◽  
Reference Range ◽  
Free Thyroxine ◽  
Reference Ranges ◽  
Free Triiodothyronine ◽  
Serum Free ◽  
Young Subjects ◽  
Age Range

SummaryAge-related trends in serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations were measured in 7248 euthyroid subjects (age-range 3 months to 106 years). 5700 were patients referred to hospitals for investigation of suspected thyroid dysfunction, but who were diagnosed euthyroid. 1548 were healthy blood donors (age-range 18-63 years) with no indication of thyroid dysfunction. FT4 concentrations were little affected by the age, the sex or the state of health of the subjects in either group. Serum FT3 concentrations were significantly affected by both age and health factors. The upper limit of the euthyroid reference range for young subjects up to 15 years was about 20% higher (10.4 pmol/1) than for adult subjects older than 25 years (8.8 pmol/1). The change in the upper limits typical of young subjects to that typical of adults occurred steadily over the decade 15–25 years. After this age, little further change occurred, especially in healthy subjects. Additionally, the lower limit of the euthyroid range for FT3 was extended by the inclusion in the reference group of patients referred to hospitals. Compared with the lower limit of the FT3 range for healthy subjects (5 pmol/1), the corresponding limit for referred subjects (young or adult) was 3.5–3.8 pmol/1. Broadening of the FT3 reference range was probably brought about by a significant number of patients in the hospital-referred group with the “1OW-T3 syndrome” of mild non-thyroidal illness. Accordingly, FT3 was inferior to FT4 in the discrimination of hypothyroidism, as FT4 was unaffected by this phenomenon. Effects of age and non-thyroidal illness on serum FT3 concentrations require great care when selecting subjects for a laboratory euthyroid reference range typical of the routine workload. Constraints on the choice of subjects for FT4 reference ranges are less stringent.

scholarly journals Plasma mineral (selenium, zinc or copper) concentrations in the general pregnant population, adjusted for supplement intake, in relation to thyroid function

2020 ◽  
Vol 125 (1) ◽  
pp. 71-78
Author(s):  
Victor Pop ◽  
Johannes Krabbe ◽  
Wolfgang Maret ◽  
Margaret Rayman
Keyword(s):  
Thyroid Function ◽  
Reference Range ◽  
First Trimester ◽  
Future Research ◽  
Thyroid Peroxidase ◽  
Reference Ranges ◽  
Lower Plasma ◽  
The Mean ◽  
The Impact ◽  
Supplement Intake

AbstractThe present study reports on first-trimester reference ranges of plasma mineral Se/Zn/Cu concentration in relation to free thyroxine (FT4), thyrotropin (TSH) and thyroid peroxidase antibodies (TPO-Ab), assessed at 12 weeks’ gestation in 2041 pregnant women, including 544 women not taking supplements containing Se/Zn/Cu. The reference range (2·5th–97·5th percentiles) in these 544 women was 0·72–1·25 µmol/l for Se, 17·15–35·98 µmol/l for Cu and 9·57–16·41 µmol/l for Zn. These women had significantly lower mean plasma Se concentration (0·94 (sd 0·12) µmol/l) than those (n 1479) taking Se/Zn/Cu supplements (1·03 (sd 0·14) µmol/l; P < 0·001), while the mean Cu (26·25 µmol/l) and Zn (12·55 µmol/l) concentrations were almost identical in these sub-groups. Women with hypothyroxinaemia (FT4 below reference range with normal TSH) had significantly lower plasma Zn concentrations than euthyroid women. After adjusting for covariates including supplement intake, plasma Se (negatively), Zn and Cu (positively) concentrations were significantly related to logFT4; Se and Cu (but not Zn) were positively and significantly related to logTSH. Women taking additional Se/Zn/Cu supplements were 1·46 (95 % CI 1·09, 2·04) times less likely to have elevated titres of TPO-Ab at 12 weeks of gestation. We conclude that first-trimester Se reference ranges are influenced by Se-supplement intake, while Cu and Zn ranges are not. Plasma mineral Se/Zn/Cu concentrations are associated with thyroid FT4 and TSH concentrations. Se/Zn/Cu supplement intake affects TPO-Ab status. Future research should focus on the impact of trace mineral status during gestation on thyroid function.

scholarly journals The Relationship between Thyroid Function and Depressive Symptoms—the FIN-D2D Population-Based Study

2015 ◽  
Vol 8 ◽  
pp. CMED.S24111 ◽  
Author(s):  
Juha Saltevo ◽  
Hannu Kautiainen ◽  
Pekka Mäntyselkä ◽  
Antti Jula ◽  
Sirkka Keinänen-Kiukaanniemi ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Depressive Symptoms ◽  
Thyroid Function ◽  
Participation Rate ◽  
Population Based ◽  
Thyroid Stimulating Hormone ◽  
Free Triiodothyronine ◽  
Population Based Study ◽  
The Mean ◽  
The Relationship

The association between thyroid function and depression is controversial. Both conditions express many similar symptoms, but the studies done give conflicting results. This study draws on a random, population-based sample of 4500 subjects aged 45–75 years old from Finland. The basic clinical study was done in 2007 for 1396 men and 1500 women (64% participation rate). Thyroid stimulating hormone (TSH), free thyroxine (F-T4), and free triiodothyronine (F-T3) were measured in 2013 from frozen samples. The 21-item Beck Depression Inventory (BDI-21) was applied to assess depressive symptoms (score ≥10 points). The prevalence of depressive symptoms was 17.5% in women and 12.5% in men. In women, the mean levels of TSH, F-T4, and F-T3 without depressive symptoms vs. with the presence of depressive symptoms were 1.92/1.97 mU/L, 13.1/13.1 pmol/L, and 3.91/3.87 pmol/L (NS), respectively. In men, the levels were 1.87/1.94 mU/L, 13.5/13.7 pmol/L, and 4.18/4.12 pmol/L (NS), respectively. In multiple regression analysis, TSH had no relationship to BDI-21 total score. We found no association between depressive symptoms and thyroid values.

Interference of Plasma Fluorophores on the Red Blood Cell Zinc Protoporphyrin : Haemoglobin Ratio as Determined on a Haematofluorimeter

1989 ◽  
Vol 26 (4) ◽  
pp. 368-373 ◽  
Author(s):  
P C Bartels ◽  
P W Helleman ◽  
J B J Soons
Keyword(s):  
Blood Cells ◽  
Extraction Method ◽  
Isotonic Saline ◽  
Zinc Protoporphyrin ◽  
Reference Ranges ◽  
Reference Groups ◽  
Blood Samples ◽  
Mean Values ◽  
Good Relationship ◽  
The Mean

Direct measurement of the zinc protoporphyrin:haemoglobin ratio (ZPP: Hb ratio) in blood samples is performed by using a haematofluorimeter. Interference by non-specific fluorophores can be eliminated by removing the plasma and making the measurement on washed red blood cells (RBCs). After re-suspending RBCs in isotonic saline, haematofluorimeter readings for the ZPP: Hb ratios revealed higher stability in the course of time whereas a good relationship was found with results obtained by application of an extraction method. Separate reference ranges were established for adult male and female subjects. After washing, the mean values calculated for ZPP: Hb ratios of subjects belonging to the reference groups demonstrated a reduction of 0·04 μmol ZPP mol Hb, corresponding with approximately 30%. In the patients' group, application of washing resulted in a variable decrease of ZPP: Hb ratios.

scholarly journals Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects

2018 ◽  
Vol 56 (8) ◽  
pp. 1309-1318 ◽  
Author(s):  
Abdurrahman Coşkun ◽  
Anna Carobene ◽  
Meltem Kilercik ◽  
Mustafa Serteser ◽  
Sverre Sandberg ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Complete Blood Count ◽  
Hematological Parameters ◽  
Hemoglobin Concentration ◽  
Biological Variation ◽  
Mean Corpuscular Hemoglobin ◽  
Mean Values ◽  
Performance Specifications ◽  
The Mean ◽  
Variance Homogeneity

Abstract Background: The complete blood count (CBC) is used to evaluate health status in the contexts of various clinical situations such as anemia, infection, inflammation, trauma, malignancies, etc. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are required. The study aim was to define the BVs of CBC parameters employing a strict protocol. Methods: Blood samples, drawn from 30 healthy subjects (17 females, 13 males) once weekly for 10 weeks, were analyzed using a Sysmex XN 3000 instrument. The data were assessed for normality, trends, outliers and variance homogeneity prior to coefficient of variation (CV)-analysis of variance (ANOVA). Sex-stratified within-subject (CVI) and between-subjects (CVG) BV estimates were determined for 21 CBC parameters. Results: For leukocyte parameters, with the exception of lymphocytes and basophils, significant differences were found between female/male CVI estimates. The mean values of all erythrocyte-, reticulocyte- and platelet parameters differed significantly between the sexes, except for mean corpuscular hemoglobin concentration, mean corpuscular volume and platelet numbers. Most CVI and CVG estimates appear to be lower than those previously published. Conclusions: Our study, based on a rigorous protocol, provides updated and more stringent BV estimates for CBC parameters. Sex stratification of data is necessary when exploring the significance of changes in consecutive results and when setting analytical performance specifications.

Observational study to define reference ranges for the 3% oxygen desaturation index during sleep in healthy children under 12 years using oximetry motion-resistant technology

2020 ◽  
pp. archdischild-2020-320066 ◽  
Author(s):  
Jonathan Wen Yi Ong ◽  
Daniel Williams ◽  
Johanna C Gavlak ◽  
Natasha Liddle ◽  
Paula Lowe ◽  
...  
Keyword(s):  
Pulse Oximetry ◽  
Sleep Disordered Breathing ◽  
Oxygen Desaturation ◽  
Reference Ranges ◽  
Healthy Children ◽  
Mean Values ◽  
Desaturation Index ◽  
Oxygen Desaturation Index ◽  
The Mean ◽  
Pulse Oximeters

ObjectiveTo define reference ranges for the 3% oxygen desaturation index (DI3) in healthy children under 12 years old during sleep.DesignObservational.SettingHome.SubjectsHealthy children aged 6 months to 12 years of age.InterventionNocturnal pulse oximetry at home. Parents documented sleep times. Visi-Download software (Stowood Scientific) analysed data with artefact and wake periods removed.Main outcome measuresThe following oximetry parameters used in the assessment of sleep-disordered breathing conditions were measured: 3% (DI3) and 4% (DI4) oxygen desaturation indices—the number of times per hour where the oxygen saturation falls by at least 3% or 4% from baseline, mean saturations (SAT50), minimum saturations (SATmin), delta index 12 s (DI12s), and percentage time with saturations below 92% and 90%.ResultsSeventy-nine children underwent nocturnal home pulse oximetry, from which there were 66 studies suitable for analysis. The median values for DI3 and DI4 were 2.58 (95% CI 1.96 to 3.10) and 0.92 (95% CI 0.73 to 1.15), respectively. The 95th and 97.5th centiles for DI3 were 6.43 and 7.06, respectively, which inform our cut-off value for normality. The mean values for SAT50 and SATmin were 97.57% (95% CI 97.38% to 97.76%) and 91.09% (95% CI 90.32% to 91.86%), respectively.ConclusionIn children aged 6 months to 12 years, we define normality of the 3% oxygen desaturation index as <7 using standalone, motion-resistant pulse oximeters with short averaging times.

Lacking evidence for release of thyroid hormones from circulating thyroglobulin during subtotal thyroidectomy

1988 ◽  
Vol 117 (2) ◽  
pp. 219-224 ◽  
Author(s):  
J. Date ◽  
M. Blichert-Toft ◽  
U. Feldt-Rasmussen ◽  
V. Haas
Keyword(s):  
Thyroid Hormones ◽  
Mean Value ◽  
Thyroid Stimulating Hormone ◽  
Mean Values ◽  
Thyroid Resection ◽  
Free Thyroxine Index ◽  
Total Triiodothyronine ◽  
Total Thyroxine ◽  
The Mean ◽  
Peak Value

Abstract. The effect of subtotal thyroid resection for thyrotoxicosis on concentrations of serum thyroid hormones and thyroglobulin (Tg), was determined in 10 patients during operation and the subsequent 18 days. Mean serum Tg responded drastically, increasing from a pre-operative value of 0.30 nmol/l to a peak value of approximately 26 nmol/l during operation followed by a gradual decline to levels lower than before surgery on day 18. Mean serum total thyroxine was 114 nmol/l pre-operatively and free thyroxine index (FT4I) 105 units. Both fluctuated only slightly during operation. Postsurgically, the mean values decreased to below 50% of the pre-operative level. Mean serum total triiodothyronine (TT3) was 1.46 nmol/l pre-operatively. It decreased during operation, reaching a nadir of 0.55 nmol/l on day 2, whereafter the concentration increased slightly. Mean serum reverse T3 (rT3) was 0.45 nmol/l pre-operatively, increased 62% during surgery, and decreased postsurgically. The mean value of serum thyroid stimulating hormone (TSH) was 0.61 mU/l pre-operatively and remained below 1 mU/l during and after operation, but from day 10 concentration began to rise steadily. It is concluded that the vast release of Tg during thyroid resection did not contribute to the concentration of serum T4 to an extent of clinical relevance.

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