Reference intervals on the Abbot Architect for serum thyroid hormones, lipids and prolactin in healthy children in a population-based study

Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age- and gender- specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.     

Reference intervals on the Abbot Architect for serum thyroid hormones,lipids and prolactin in healthy children in a population-based study

Abstract

Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age- and gender- specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.     

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

Abstract Background: The aim of the present study was to establish Nordic reference intervals for thyreotropin (TSH) and the thyroid hormones in heparinized plasma. Methods: 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((R)) and thyroid peroxidase antibodies (TPO-ab) were measured using the Brahms Kryptor assay. Results: 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. Conclusions: 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.     

Reference intervals for reproductive hormones in prepubertal children on the automated Roche cobas e 411 analyzer

ObjectivesTo establish reference intervals for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P), total and free testosterone (T) and sex-hormone binding globulin (SHBG) in prepubertal children and to assess age- and gender-related differences.Design and methodsA total of 948 subjects, 480 girls and 468 boys, between 1 and 11 years of age, were included in this study. All assays were performed on a Roche cobas e 411 immunoassay analyzer. Reference intervals have been evaluated according to the most recent CLSI guidelines.ResultsMedian values of LH, FSH and T were significantly higher in subgroups ranging from ≥ 8 to < 11 years, for both genders. In girls of that age, reference values of E2 were significantly higher than in younger ones, and in boys of the corresponding age.ConclusionEstablished reference intervals are applicable to other laboratories that use the same instrumentation.     

Reference intervals for circulating angiogenic cytokines.

BACKGROUND: The levels of angiogenic cytokines are important in the definition of baseline characteristics of cancers and to predict patient prognosis; however, the reference intervals for angiogenic cytokines have received only limited attention. Herein, we obtained reference intervals for angiogenic cytokines, including vascular endothelial growth factor (VEGF), hepatocyte growth factor, basic fibroblast growth factor, interleukin-6, vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2. METHODS: We measured these materials in serum, plasma and urine of 131 controls, according to the guidelines of the Clinical and Laboratory Standards Institute. We analyzed the association between angiogenic cytokine levels and other laboratory parameters and explored whether polymorphisms in angiogenic cytokine genes affect the levels of cytokines. RESULTS/CONCLUSIONS: These data allowed us to construct reference intervals for angiogenic cytokines, and we also observed that concentrations of angiogenic cytokines generally do not vary with genotype or haplotype. An exception was serum VEGF concentration; this level was marginally affected by the -1154 VEGF polymorphism.     

Reference intervals for preterm thyroid function during the fifth to seventh day of life

BackgroundDue to the lack of reference intervals for serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in preterm neonates during the 5th to 7th day of life, we performed a retrospective study using the chemiluminescence immunoassay system.MethodsA total of 2040 preterm neonates with a gestational age (GA) of 26–35 weeks in the neonatal intensive care unit from 2014 to 2019 were included. Their serum FT3, FT4 and TSH values were calculated and analyzed to establish reference intervals for preterm neonates stratified by GA. The comparisons of FT3, FT4 and TSH were made by sex (males and females) and gestational age (26–28 weeks; 29–32 weeks; 33–35 weeks).ResultsThe reference intervals for FT3, FT4 and TSH in preterm neonates with a GA of 26–35 weeks were (1.65~5.21) pmol/L, (8.64~25.41) pmol/L, and (0.406~12.468) mlU/L, respectively. There were significant differences between serum FT3 and FT4 values and GA, while TSH levels were not significantly different (P < 0.01). The serum FT3 values of males were lower than those of females, especially in the 29–32 weeks group. No significant differences in serum values between sexes were found in FT4 or TSH (P > 0.05).ConclusionReference intervals of thyroid function tests were established to determine the early diagnostic criteria of thyroid diseases for neonates with a GA of 26–35 weeks and to avoid unnecessary retesting and interventions. The reference intervals of FT4 can be used as an indicator to regulate the doses of thyroid hormone supplement in the treatments of congenital hypothyroidism.     

New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid

BACKGROUND: The aim of our present study was to establish new reference intervals for thyrotropin (TSH) and thyroid hormones based on National Academy of Clinical Biochemistry (NACB) criteria and regular thyroid ultrasonography. We also assessed the effect of potentially confounding factors to modulate the limits of these intervals. METHODS: We investigated 870 apparently healthy persons and excluded, step by step, those with a family history of thyroid disease, pathologic thyroid ultrasonography results, and increased anti-thyroid peroxidase or anti-thyroglobulin antibodies. Accordingly, only 453 of the 870 persons in the entire group were finally included as reference collective. We measured serum concentrations of TSH, total and free thyroxine (T(4) and FT(4)), and total and free triiodothyronine (T(3) and FT(3)) of the whole and the reference collective on the ELECSYS system assays (Roche Diagnostics) and calculated the 2.5th and 97.5th percentiles for comparison. RESULTS: The calculated lower limit for TSH differed significantly between the reference intervals for healthy persons with an assessed normal thyroid gland vs the nonselected group of healthy blood donors. Age was the only independent factor and was significantly inversely associated with TSH (P <0.0001). Use of oral contraceptives was a significant predictor for variation in T(4) concentrations (P <0.001). Age and oral contraceptives were independently associated with T(3) variations (P <0.05). For FT(4) vs FT(3) variation, gender and (inversely) age (P <0.01) were independent modulating factors. CONCLUSIONS: The selection of healthy persons according to NACB criteria combined with sonographic confirmation of a normal thyroid gland provide a valid basis for the reference interval for TSH. Factors indicating a preclinical disease state, such as family history, pathologic ultrasonography result, or increased anti-thyroid peroxidase and anti-thyroglobulin antibodies, can be associated with normal hormone concentrations. Additionally, patient age and gender as well as use of contraceptives should be considered in diagnostic evaluation of thyroid diseases.     

Reference intervals for absolute and percentage immature platelet fraction using the Sysmex XN-10 automated haematology analyser in a UK population

Background: Immature platelet fraction (IPF) estimation is a non-invasive and sensitive test that is available on recently introduced Sysmex XN-series of automated haematology analysers. It is a direct cellular indicator of thrombopoiesis. The aim of this study was to establish reference intervals for IPF, for both absolute (A-IPF) and percentage (%-IPF) measurements.

Material and methods: A total of 2366 samples that met the inclusion criteria were assayed for full blood count on the Sysmex XN-10 and a non-parametric percentile method was used for calculating the reference intervals.

Results: After the outliers were excluded, the reference interval for %-IPF and A-IPF on Sysmex XN-10 were 1.6–10.1% and 4.37–23.21?×?10⁹/L in total individuals, respectively. There was a statistical significance noted between the sexes (p?=?.004) for %-IPF, therefore a sex-specific reference interval was established, which was 1.8–10.0% for the males and 1.5–10.1% for females. No significant difference in sex status for A-IPF and age status for both %-IPF and A-IPF was observed. A very poor correlation was estimated between age versus %-IPF, ρ?=?0.0156, and age versus A-IPF, ρ?=??0.0023, indicating that there is no overall biological relationship between age and these parameters. As expected, a strong correlation between %-IPF and A-IPF was noted which could be attributed to their inter-relatedness.

Conclusions: This large-scale study showed comparable reference intervals with the previous studies for %-IPF and A-IPF in a UK population. It found the need to establish sex-specific reference intervals for %-IPF, but not for A-IPF, whereas reference intervals were found to be stable across the age range.     

A model for a multicentre approach to the derivation of reference intervals for thyroid hormones and testosterone for laboratories using identical analysers.

Ideally, every laboratory should derive their own reference intervals for all analytes, but this is difficult in practice. A survey, by questionnaire, of UK laboratories using the Chiron Diagnostics ACS:180 (Chiron Diagnostics Limited, Halstead, Essex, UK), for thyroid function tests, showed that 10% of laboratories derived their own reference intervals, 60% quoted values "adapted" from intervals for previous methods, whilst the remaining 40% quoted (often incorrectly) reference intervals supplied by the manufacturer. In addition only 13% of respondent laboratories derived their own reference intervals for testosterone. As a result of this survey, a study was devised to enable the users of the Chiron Diagnostics ACS:180 immunoassay system to develop and use within-method, between-laboratory reference intervals for thyroid hormones and testosterone. Laboratory collaboration provided the recommended minimum number of data points by establishing a reference sample group. This sample group was used for the calculation of appropriate reference intervals for each hormone according to the guidelines published by the IFCC. We propose this approach as a model for laboratories using identical instrumentation to produce, through collaboration, within-method, between laboratory reference intervals.     

Reference intervals for the P-Albumin bromocresol purple method

Correct reference intervals are an important part of test results. As establishing own reference intervals is a very expensive task, the NORIP reference intervals are often transferred for use in Nordic laboratories. The NORIP reference interval on P-Albumin was here compared to current results for laboratories using the bromocresol purple (BCP) method for P-Albumin. External quality control reports were used to investigate the change in levels between the BCP and BCG methods on P-Albumin. An algorithm was built for extracting and isolating the laboratory’s healthy subject population. The algorithm was used to extract test results from the laboratory information system. Parametric and non-parametric statistical methods were used to evaluate the P-Albumin test result populations. The indirect method used here clearly shows that the NORIP reference intervals for P-Albumin are not fit for the current bromocresol purple methods. The method was also used to suggest new reference interval limits.     

Reference intervals for TSH and thyroid hormones are mainly affected by age, body mass index and number of blood leucocytes, but hardly by gender and thyroid autoantibodies during the first decades of life

Objectives

The purpose of our study was to establish reference intervals for thyroid function tests in children and adolescents and to identify factors that may influence the limits of these intervals.

Methods

TSH, FT3, FT4, T3, T4, t-uptake, TPO-antibody (TPO-Ab) and TG-antibody (TG-Ab) levels were determined in blood of 1004 infants, children and adolescents by the Elecsys system (Roche).

Results

A distinct overall age-dependent decrease of analyte levels was found for all parameters investigated. Puberty was accompanied by an increase of TSH, FT3 and T3 levels. Results of T4 and t-uptake were significantly higher in girls compared to boys. The exclusion of children with increased TPO-Ab and TG-Ab had no significant effect on the limits of the reference interval. We found that besides age, BMI-SDS but also white blood cells count and gender played a role in the prediction of analyte variation.

Conclusions

Covariates like BMI-SDS and white blood cell count should be taken into consideration when interpreting TSH and thyroid hormone measurements as well whereas gender and TPO-Ab or TG-Ab play a minor role.     

Gap analysis of pediatric reference intervals related to thyroid hormones and the growth hormone-insulin growth factor axis

Efficacy of laboratory medicine in assisting attending physicians in their diagnostic and follow-up endeavors is intimately linked to an access to meaningful and reliable reference values. Pediatrics is particularly sensitive to this problem as the processes, associated with growth and development, are imposing rapid discontinuous changes on the physiology of the individuals. Some developmental stages are more critical than others. The neonatal and the pubertal periods, for which we lack reference ranges, are two such examples. Beyond biological considerations, we realize that, over the last 2 decades, technology has evolved, both at the analytical and reagent levels. This technological evolution inexorably leads to the need in redefining reference values. It is for this reason that a group of clinical and medical biochemists have joined their efforts in creating the Canadian Laboratory Initiative in Paediatric Reference (CALIPER) which objective is to define a pan-Canadian set of reference values from birth to late adolescence. To illustrate the need of such a venture, a brief gap analysis for biochemical variables related to the thyroid function, and the growth hormone-insulin-like growth factors axis follows.     

Population-specific reference values for thyroid hormones on the Abbott ARCHITECT i2000 analyzer.

Reliable reference ranges are important in the interpretation of laboratory data, and it is incumbent on each laboratory to verify that the ranges they use are appropriate for the patient population they serve. The objective of this study was to determine population-specific reference ranges for thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and total triiodothyronine (TT3) on the Abbott ARCHITECT 12000 analyzer. For this study, we used human serum samples collected from a population in Castilla y León, Spain. Serum samples were collected from 304 individuals (male, n = 151; female, n = 153; age 12-94 years) representing outpatients (n=100), hospitalized patients (n = 104) and apparently healthy subjects (n = 100). Individuals taking any medications, with a history of thyroid disorder, or severe non-thyroidal illness were excluded from the study. For healthy subjects, the following reference intervals were determined: TSH, 0.51-5.95 mlU/l; fT4, 0.84-1.42 ng/dl (10.77- 18.21 pmol/l); fT3, 1.48-3.37 pg/ml (2.27-5.18 pmol/l); and TT3, 0.65-1.46 ng/ml (1.00-2.24 nmol/l). In this group, TSH and fT4 showed significant differences between men and women, but fT3 and TT3 did not. Conversely, fT3 and TT3 showed significant age-related differences, but TSH and fT4 did not. Within the outpatient group, no significant differences were seen between men and women for any of the hormones, but age-related differences were significant for fT3 and TT3. Within the hospitalized patient group, significant differences between men and women were found for TSH only, and age-related differences were significant for TSH, fT3 and TT3. Our findings are basically in accordance with previously published results for fT3, TT3 and TSH, but for fT4 our results differ from other data in the literature. This highlights the need for laboratories to confirm that the reference ranges they use are appropriate for the population they serve.