National Academy Of Clinical Biochemistry Research Articles

A-060 Thyroid Laboratory Database Assessment Shows that Total Triiodothyronine Significantly Decreases with Age

Abstract Introduction The effects of aging on human thyroid function are well studied in relationship to thyroid stimulating hormone (TSH) and free tiroxine (FT4); TSH increases, while FT4 decreases with age. Although animal studies show that total triiodotironine (TT3) is lower in aged male rats, these changes are still not clear enough in humans. The National Academy of Clinical Biochemistry (NACB) suggests that TT3 levels would be lower in subjects over 60 years (y.), but the number of elderly assessed was too small for a robust statistical analysis. In search on PubMed, crosschecking the terms elderly/age/aging, with triiodothyronine/T3/total T3, there are a few studies available using current assays with a significant number of patients. Therefore, the demonstration of how the TT3 performs with age is still an opened question. Objective The aim of this study was to observe if TT3 changes significantly with age. Methods We, retrospectively, analyzed blood samples requesting serum TT3 of unique patients, who had TSH measured on the same day; and thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), anti TSH receptor antibodies (TRAb) or TSH receptor-stimulating immunoglobulin (TSI) at any time since patient admission. Subjects were adults ≥20 y., admitted to a private reference clinical laboratory in Brazil, from January 01, 2014 to December 31, 2022, using anonymized data. Serum TT3 was measured in Cobas Roche, by electrochemiluminescence assay, reference interval 70–210 ng/dL. Exclusion criteria were (and/or): tests performed in hospitals, use of drugs that could interfere on TT3 or TSH, TSH ≤ 0.1 mIU/L or ≥10.0 mIU/L, and any positive antibody at any time. The level of statistical significance was P < 0.05. Results Initially, 959 297 records from the database were surveyed. After applying the exclusion criteria, 141 819 subjects were eligible: mean age = 45 y.; median = 42 y., 62% female (F). Statistically significant differences - P < 0.05 for all comparisons between groups - were found by age and gender in TT3 mean values (in ng/dL). Regarding age: from 20 to 59 y. = 120 ± 26.6; 60 to 79 y. = 109 ± 20.7; and 80 y. and over = 97.2 ± 20.0. By gender: F = 120 ± 28.9; male = 114 ± 20.4. It was also observed that, in elderly, while TT3 decreases, TSH increases (results not shown). Comparing TT3 means by age groups, it is 9% lower in subjects aged 60–79 y. and 19% lower in those aged 80 y. and older, compared to younger (20–59 y.) subjects. Conclusion TT3 results is influenced by several factors, including age, gender and laboratory assay. As far as we know, searching in PubMed, this is the largest collection of data on the relationship between TT3 and age. The data obtained showed a statistically significant decrease in TT3 in elderly, and mainly in very elderly, and higher levels in women than in men. This finding draws call attention to the fact that these parameters should taken into account when evaluating TT3 levels.

Analysis of Sensitivity, Specificity, and Predictive Values of High-Sensitivity Troponin T in a Secondary Care Setting: A Retrospective Cohort Study.

Background High-sensitivity cardiac troponin (hs-cTn) assays have significantly improved the early detection of myocardial injury and the diagnosis of acute coronary syndrome(ACS). Different diagnostic algorithms exist for the interpretation of hs-cTn in the management of patients with suspected ACS. This study analysed the diagnostic efficacy of hs-cTn using serial and single measurements while also shedding light on the challenges associated with the use of this assay. Methods We reviewed 189 results belonging to 120 unique patient episodes and records for troponin tests performed in a two-week period obtained from the West Cumberland Hospital, North Cumbria Integrated Care (NCIC), Whitehaven, England. These troponin tests were carried out based on the NCIC trust guidelines for the use of troponin assays in the management of acute coronary syndrome(ACS). A positive troponin test is defined using the NCIC trust guidelines and the National Academy of Clinical Biochemistry (NACB) guidelines. The case notes of the unique patients were reviewed to determine the outcome, which is defined as the clinical diagnosis on discharge of the patient following a cardiologist review. These outcomes were then used to calculate the sensitivity, specificity, and predictive values. We also determined the alternate diagnosis for false-positive tests. Results Using both guidelines to assess the clinical effectiveness of the troponin assay yields slightly varying results, with the single positive test of NACB demonstrating a higher sensitivity of 92.8% (>71.4%) and a slightly better negative predictive value of 97.8% (>96%). However, using the serial troponin measurements as per the NCIC trust guideline demonstrates a better specificity of 95.2% (>42.4%) and a positive predictive value of 66% (>17.5%). False positive results are identified, which are due to alternate diagnoses such as stable angina, myocarditis, heart failure, sepsis, and malignancy. Conclusion High-sensitivity troponin (hs-cTn) assays play a crucial role in the early detection and management of patients with suspected ACS. This study supports evidence that serial troponin measurements are more diagnostically accurate than single troponin measurements. Although hs-cTn assays offer significant advantages, there remain challenges and limitations that require careful interpretation and clinical correlation.

The issues and challenges with cancer biomarkers.

A biomarker is a measurable indicator used to distinguish precisely/objectively either normal biological state/pathological condition/response to a specific therapeutic intervention. The use of novel molecular biomarkers within evidence-based medicine may improve the diagnosis/treatment of disease, improve health outcomes, and reduce the disease's socio-economic impact. Presently cancer biomarkers are the backbone of therapy, with greater efficacy and better survival rates. Cancer biomarkers are extensively used to treat cancer and monitor the disease's progress, drug response, relapses, and drug resistance. The highest percent of all biomarkers explored are in the domain of cancer. Extensive research using various methods/tissues is carried out for identifying biomarkers for early detection, which has been mostly unsuccessful. The quantitative/qualitative detection of various biomarkers in different tissues should ideally be done in accordance with qualification rules laid down by the Early Detection Research Network (EDRN), Program for the Assessment of Clinical Cancer Tests (PACCT), and National Academy of Clinical Biochemistry. Many biomarkers are presently under investigation, but lacunae lie in the biomarker's sensitivity and specificity. An ideal biomarker should be quantifiable, reliable, of considerable high/low expression, correlate with the outcome progression, cost-effective, and consistent across gender and ethnic groups. Further, we also highlight that these biomarkers' application remains questionable in childhood malignancies due to the lack of reference values in the pediatric population. The development of a cancer biomarker stands very challenging due to its complexity and sensitivity/resistance to the therapy. In past decades, the cross-talks between molecular pathways have been targeted to study the nature of cancer. To generate sensitive and specific biomarkers representing the pathogenesis of specific cancer, predicting the treatment responses and outcomes would necessitate inclusion of multiple biomarkers.

852-P: Precision of the Afinion HbA1c Dx Point-of-Care Test in CLIA Waived Settings

There is limited data on the performance of point of care HbA1c assays when fingerstick samples are tested by intended users in CLIA waived settings. This study evaluated the precision of the Afinion HbA1c Dx (Afinion) when performed at CLIA waived sites (N=5) by operators with no laboratory training. The operators (N=12) self-trained using the materials provided with test purchase, had no prior Afinion system experience, and did not observe one another during testing. For each subject enrolled in the study (N=115) , 2 operators each obtained 2 fingerstick samples (4 total fingersticks per subject) and tested one sample on each of 2 Afinion instruments. The repeatability, between-operator, and between-instrument components of variance were calculated using the REML method for each of 4 HbA1c concentration intervals. The total imprecision was calculated as a composite of 6 relevant components of variance, including a) the components of variance estimated here (repeatability, between-operator, and between-instrument) , and b) components of variance estimated in prior studies (between-run, between-day, and between-lot) . The repeatability was the dominant component, ranging from 0.83-1.14% CV across the HbA1c concentration intervals. The between-operator component was 0.00% CV for 3 out of the 4 HbA1c intervals, and was only 0.19% CV in the remaining interval, indicating the precision of the test is not operator dependent. The between-instrument component ranged from 0.22-0.39% CV. When combined with the other components of variance estimated in prior studies, the total imprecision does not exceed 1.80% CV, which is below the National Academy of Clinical Biochemistry’s (NACB) recommendation for a single method, interlaboratory CV of <3%. The results were similar to those obtained by trained operators testing fingerstick samples with the Afinion system. These results indicate that the precision of the Afinion is comparable to many laboratory HbA1c assays, and suitable for use in CLIA waived settings. Disclosure M.Clendenin: Employee; Abbott. N.Ahmed: Employee; Abbott. K.Kupfer: Employee; Abbott. C.L.Green: Employee; Abbott Diagnostics, Siemens. K.S.Fortner: Employee; Abbott. T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker's Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. S.Brick: None. S.I.Smiley: None. G.S.Strauss: None. A.A.Thorsell: None.

The Analytical Reliability of the Oral Glucose Tolerance Test for the Diagnosis of Gestational Diabetes: An Observational, Retrospective Study in a Caucasian Population.

The Oral Glucose Tolerance Test (OGTT) is currently the gold standard reference test for the diagnosis of gestational diabetes mellitus (GDM). Several critical issues related to analytical variables have challenged its reproducibility and accuracy. This study aimed to assess the analytical reliability of the OGTT for the diagnosis of GDM. A total of 1015 pregnant women underwent a 2 h 75 g OGTT between 24 and 28 weeks of gestation. As recommended by National Academy of Clinical Biochemistry, we considered the total maximum allowable error for glucose plasma measurement as <6.9%. Assuming the possibility of analytical errors within this range for each OGTT glucose plasma value, different scenarios of GDM occurrence were estimated. GDM prevalence with standard criteria was 12.2%, and no hypothetical scenarios have shown a comparable GDM prevalence. Considering all the three OGTT values estimated at the lowest or the highest allowed value according to total maximum allowable error, GDM prevalence significantly varied (4.5% and 25.3%, respectively). Our results indicate that the OGTT is not completely accurate for GDM diagnosis.

Reference Intervals for Serum Thyroid-Stimulating Hormone Based on a Recent Nationwide Cross-Sectional Study and Meta-Analysis.

ObjectiveThe aim of our study was to compare the reference intervals (RIs) [median (2.5th-97.5th percentiles)] for thyroid-stimulating hormone (TSH) between subgroups stratified by ethnicity and iodine status in a global context.Design and MethodsPrimary data were derived from a recently published cross-sectional study in mainland China. Secondary data were obtained from online databases. The RIs for TSH were calculated in the reference population according to the National Academy of Clinical Biochemistry (NACB) standard and in the disease-free population. A meta-analysis of ethnicity- and iodine status-specific TSH RIs was performed.ResultsThe primary data showed that the TSH RI (mU/L) in the disease-free population was 2.33 (0.67, 7.87), which is wider than the published RI [2.28 (0.74, 7.04)] in the reference population. The meta-analysis showed that whether in the reference or disease-free population, the RIs in Yellows were much higher than those in Caucasians. In the reference population, the median and 2.5th percentile in the iodine-sufficient subgroup were both lower than the iodine-deficient or more-than-adequate subgroup, while the 97.5th percentile showed a positive trend with increasing sufficiency of iodine. However, in the disease-free population, the iodine-sufficient subgroup had a lower median and 97.5th percentile but higher 2.5th percentile than the iodine-deficient subgroup.ConclusionYellows have a higher TSH RI than Caucasians. In the reference population, both the median and 2.5th percentile TSH in the iodine-sufficient population were the lowest among the different iodine status subgroups, while the 97.5th percentile of TSH showed an upward trend with increasing iodine sufficiency.

Estimated change in prevalence of abnormal thyroid-stimulating hormone levels in China according to the application of the kit-recommended or NACB standard reference interval.

BackgroundBoth the kit-recommended and United States National Academy of Clinical Biochemistry (NACB) standard thyroid-stimulating hormone (TSH) reference intervals (RIs) are used to determine thyroid dysfunction in clinical practice and epidemiological surveys in China. However, a number of kit-recommended RIs were derived from the European or United States reference population.MethodsA nationally representative cross-sectional study with 78,470 enrolled participants aged 18 years or older from China was performed. Serum concentrations of thyroid hormones, TSH, thyroid antibodies (by Roche Diagnostics), and urine iodine concentration (UIC) were measured.FindingsThe abnormal TSH weighted prevalence was 15.33% (95% CI, 14.24% to 16.49%) according to the kit-recommended RI and 6.89% (6.46% to 7.34%) according to the NACB standard RI. The NACB standard prevalence of abnormal TSH was associated with an absolute change in abnormal TSH prevalence of −11.20% (−12.23% to −10.18%) among women. When estimating the proportion of supranormal TSH levels according to background characteristics, the NACB standard definition decreased the prevalence by more than 10% in some categories, with the highest absolute difference of −13.92% (−15.52% to −12.33%) observed among the elderly, −12.85% (−13.68% to −12.02%) among those with UIC ≥300 μg/L, and −12.15% (−13.02% to −11.28%) among non-smokers. For subnormal TSH, with the highest absolute difference of 3.17% (2.74% to 3.61%) observed among regular smokers, 3.11% (2.49% to 3.74%) among the elderly, and 2.53% (2.29% to 2.77%) among those with BMI <25.InterpretationFor adults in China, the NACB standard RI of TSH reveals a lower estimated prevalence of supranormal TSH levels than the kit-recommended RI. Because of the public health significance of overt and subclinical hypothyroidism and the very large population base in China, the TSH RI should be further assessed.FundingNational Health Commission of the People's Republic of China and National Natural Science Foundation of China.

A Thyroid Stimulating Hormone Reference Range: Iranian Thyroid Cohort study.

Background:Current reference values for thyroid function tests are derived from data from different ethnicities and geographical areas. In this article, we aim to select criteria from the guidelines proposed by the National Academy of Clinical Biochemistry (NACB) and to determine the TSH and T4 reference limits in the iodine-sufficient area of Isfahan, a metropolitan city in Iran.Materials and methods:This study was conducted within the framework of “Isfahan Thyroid Study (ITS)”, an ongoing prospective cohort that started in 2006 (n=2523) until 2011 (n=711) and included participants above the age of twenty. We measured TSH, total T4, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb).Results:Recruitment was based on the NACB criteria, 1899 participants were included in 2006(58.5% male) and 377 in 2011(62.3% male). The mean± SD age was 39.66 ±12.71 and 48.96±12.35 years in 2006 and 2011, respectively. The mean± SD for TSH was 2.0±1.19 and 2.11±1.11 mU/L and T4 was 6.67±1.47 and 8.3±2.95 μg /dl in 2006 and 2011, respectively. In 2006, the 2.5th percentile of serum TSH levels was 0.4 mU/L (males: 0.4 mU/L, females: 0.5 mU/L) and the 97.5th percentile of serum TSH was 4.96 mU/L (males: 4.72 mU/L, females: 5. 3 mU/L). In 2011, the 2.5th percentile of serum TSH levels was 0.7 mU/L (males: 0.6 mU/L, females: 0.77 mU/L) and 97.5th percentiles of serum TSH was 4.9 mU/L (males: 5.7 mU/L, females: 5. 57 mU/L).Conclusion:This study determined age and sex specific TSH and T4 reference ranges in the Isfahanian population, which could theoretically enable clinicians to classify patients more accurately. (www.actabiomedica.it)

Determination of age and sex specific TSH and FT4 reference limits in overweight and obese individuals in an iodine-replete region: Tehran Thyroid Study (TTS)

ABSTRACT Introduction: To determine age and sex-specific thyrotropin (TSH) and free thyroxine (FT4) reference ranges according to body mass index (BMI) categories. Methods: With regards to the National Academy of Clinical Biochemistry (NACB) criteria, a total of 2818 individuals from the Tehran Thyroid Study population was selected and categorized in three BMI groups. Results: TSH levels did not differ significantly between BMI groups (p = .054). Females had statistically higher TSH levels than males in all BMI categories (p < .001). According to age-specific analyses, the youngest category (20–29 years) had the highest median values of serum TSH in all BMI groups. With increasing BMI, the 2.5th percentile of TSH remained approximately unchanged and the 97.5th percentile showed an increasing pattern. FT4 level was significantly higher in the normal weight group compared to obese individuals (p < .001); females had significantly lower FT4 levels than males in normal weight and obese groups (p < .001). According to age categories, the youngest group (20–29 years) had higher levels of FT4 than the elderly group in all BMI categories. A decreasing pattern in both 2.5th and 97.5th percentiles of FT4 was observed along with increasing BMI. Conclusions: Compared to the normal weight population, obese individuals have slightly lower FT4 concentrations accompanied by similar TSH levels. With increasing BMI, upper limits of TSH and FT4 show increasing and decreasing patterns, respectively.

Reference Intervals of the Ratio of Urine Iodine to Creatinine in Pregnant Women in an Iodine-Replete Area of China.

The assessment method of iodine nutrition for pregnant women lacks strong evidence-based medicine. The prevalence of iodine deficiency in pregnant women may be overestimated using urinary iodine concentration (UIC). The reference intervals of UIC-to-urinary creatinine concentration ratio (UIC/UCr) were established using a self-sequential longitudinal study of pregnant women with singleton gestation who were recruited using the criteria of the National Academy of Clinical Biochemistry in Dandong City, which is a long-term iodine-replete area. Nine thousand one hundred sixty-four pregnant women in the first trimester from Dalian City, Dandong City, and Shenyang City were included to verify our proposed reference intervals. UIC and concentrations of urinary creatinine, serum iodine, TSH, FT4, TPOAb, and TgAb were measured. The reference intervals of UIC/UCr were 38.63-489.46μg/g for the first trimester, 58.48-644.03μg/g for the second trimester, and 56.27-644.93μg/g for the third trimester. The prevalence of iodine deficiency was 49.50% using UIC as the indicator (< 150μg/L), while the prevalence was 3.28% using UIC/UCr (< 38.63μg/g). The prevalence of iodine excess was 3.21% using UIC as the indicator (> 500μg/L) while the prevalence was 1.45% using UIC/UCr (> 489.46μg/g). The highest prevalence of overt hypothyroidism and positive thyroid antibodies was in the group with UIC/UCr < 38.63μg/g. In contrast to the place of residence and age, BMI was an influencing factor for UIC/UCr. The reference intervals of UIC/UCr were established. UIC/UCr may eliminate the effect of urine volume and reflect the actual prevalence of iodine deficiency in pregnant women.

Biological variation of cardiac troponins in chronic kidney disease.

Background Patients with chronic kidney disease often have increased plasma cardiac troponin concentration in the absence of myocardial infarction. Incidence of myocardial infarction is high in this population, and diagnosis, particularly of non ST-segment elevation myocardial infarction (NSTEMI), is challenging. Knowledge of biological variation aids understanding of serial cardiac troponin measurements and could improve interpretation in clinical practice. The National Academy of Clinical Biochemistry (NACB) recommended the use of a 20% reference change value in patients with kidney failure. The aim of this study was to calculate the biological variation of cardiac troponin I and cardiac troponin T in patients with moderate chronic kidney disease (glomerular filtration rate [GFR] 30–59 mL/min/1.73 m2). Methods and results Plasma samples were obtained from 20 patients (median GFR 43.0 mL/min/1.73 m2) once a week for four consecutive weeks. Cardiac troponin I (Abbott ARCHITECT® i2000SR, median 4.3 ng/L, upper 99th percentile of reference population 26.2 ng/L) and cardiac troponin T (Roche Cobas® e601, median 11.8 ng/L, upper 99th percentile of reference population 14 ng/L) were measured in duplicate using high-sensitivity assays. After outlier removal and log transformation, 18 patients’ data were subject to ANOVA, and within-subject (CVI), between-subject (CVG) and analytical (CVA) variation calculated. Variation for cardiac troponin I was 15.0%, 105.6%, 8.3%, respectively, and for cardiac troponin T 7.4%, 78.4%, 3.1%, respectively. Reference change values for increasing and decreasing troponin concentrations were +60%/–38% for cardiac troponin I and +25%/–20% for cardiac troponin T. Conclusions The observed reference change value for cardiac troponin T is broadly compatible with the NACB recommendation, but for cardiac troponin I, larger changes are required to define significant change. The incorporation of separate RCVs for cardiac troponin I and cardiac troponin T, and separate RCVs for rising and falling concentrations of cardiac troponin, should be considered when developing guidance for interpretation of sequential cardiac troponin measurements.

Establishing thresholds and effects of gender, age, and season for thyroglobulin and thyroid peroxidase antibodies by mining real-world big data

BackgroundThyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) are cornerstone biomarkers for autoimmune thyroid diseases, and establishment of appropriate thresholds is crucial for physicians to appropriately interpret test results. Therefore, we established the thresholds of TG-Ab and TPO-Ab in the Chinese population through analysis of real-world big data, and explored the influence of age, gender, and seasonal factors on their levels. MethodsThe data of 35,869 subjects downloaded from electronic health records were analyzed after filtering based on exclusion criteria and outliers. The influence of each factor on antibody levels was analyzed by stratification. Thresholds of TG-Ab and TPO-Ab were established through Clinical Laboratory Standards Institute document C28-A3 and National Academy of Clinical Biochemistry (NACB) guidelines, respectively. ResultsThere were significant differences according to gender after age stratification; the level of TG-Ab gradually increased with age in females. There were significant differences in TG-Ab and TPO-Ab distributions with respect to age after gender stratification. Moreover, differences were observed between seasons for TG-Ab and TPO-Ab. The thresholds of TG-Ab and TPO-Ab were 107 [90% confidence interval (CI):101–115] IU/mL and 29 (90% CI: 28–30) IU/mL, respectively, using C28-A3 guidelines, but were 84 (90% l CI: 50–126) IU/mL and 29 (90% CI: 27–34) IU/mL, respectively, using NACB guidelines. ConclusionThe levels of TG-Ab and TPO-Ab were significantly affected by gender, age, and season. The thresholds for TG-Ab and TPO-Ab for the Chinese population were established by big data analysis.

The influence of different thyroid stimulating hormone cut-offs to diagnose subclinical hypothyroidism during the first trimester of pregnancy

Objective: To analyze the influence of different thyroid stimulating hormone (TSH) cut-offs to diagnose subclinical hypothyroidism (SCH) in the first trimester of gestation. Methods: A total of 896 pregnant women were enrolled in Peking University International Hospital between October 2016 and March 2018. Among them, 421 pregnant women with single fetus who were conformed to the criteria of National Academy of Clinical Biochemistry (NACB), without adverse pregnancy outcomes and obstetric complications, were selected to establish their self-sequential longitudinal reference ranges of thyroid function. Then, SCH was diagnosed in the first trimester, using different TSH cutoffs, such as the upper limit of the first trimester-specific reference range, 4.0 mU/L recommended by the 2017 Guidelines of American Thyroid Association (ATA), 5.17 mU/L (Roche reagent) recommended by 2012 Guidelines of Chinese Society of Endocrinology and Chinese Society of Perinatal Medicine, and 2.5 mU/L recommended by 2011 Guidelines of ATA, respectively. Results: The TSH reference range was 0.12-4.16 mU/L in the first trimester. Using TSH>4.16, 4.0, 5.17 and 2.5 mU/L to diagnose SCH in the first trimester, the prevalence rates were 4.35% (39/896), 5.92% (53/896), 1.56% (14/896) and 20.87% (187/896), respectively. There was no statistically significant difference between the prevalence rates of SCH using the TSH upper reference limit of 4.0 mU/L and 4.16 mU/L (P=0.134). When TSH was defined as>4.0 mU/L to diagnose SCH, the sensitivity, specificity and Youden index was 97.4%, 98.2%, and 0.956, respectively. Conclusions: The TSH upper reference limit of 4.0 mU/L recommended by 2017 Guidelines of ATA can be used as a cut-off to diagnose SCH in first trimester for the areas without trimester-specific reference ranges for TSH in China.

An Age-Specific Serum Thyrotropin Reference Range for the Diagnosis of Thyroid Diseases in Older Adults: A Cross-Sectional Survey in China.

Background: The fact that serum thyrotropin (TSH) levels increase with age may influence the diagnosis of thyroid diseases in older adults. This study aimed to establish an age-specific serum TSH reference range, examine the prevalence of thyroid diseases in older adults ≥65 years, and analyze the risk factors. Methods: A cross-sectional study of adult populations in 10 cities in China was conducted from 2010 to 2011. A total of 15,008 subjects were randomly selected and completed the present study. Urinary iodine concentration, serum TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) titers were measured. Thyroid ultrasonography and questionnaires were completed by all the subjects. When the TSH level was abnormal, free thyroxine and/or free triiodothyronine levels were measured. Results: When the reference range of the general population was used, the prevalence rates of overt hypothyroidism (Ohypo) and subclinical hypothyroidism (Shypo) in older adults ≥65 years were significantly higher than those in younger adults <65 years (2.09% vs. 0.80% and 19.87% vs. 16.23%, respectively; p < 0.001). Positive TPOAb and positive TgAb were associated with the prevalence of Shypo in older adults. An age-specific serum TSH reference range was formulated according to guidelines set forth by the National Academy of Clinical Biochemistry. Both the median and upper limit values of serum TSH in older adults were higher than those in younger adults (2.58 [0.75-8.86] mIU/L vs. 2.38 [0.76-6.57] mIU/L; p < 0.001). Using the age-specific serum TSH reference range, the prevalence of Shypo in older adults was 3.3%, which was significantly lower than the prevalence based on the reference range of the general population (3.3% vs. 19.87%). The prevalence rates of Ohypo, overt hyperthyroidism (Ohyper), and subclinical hyperthyroidism (Shyper) did not change much (Ohypo: 1.6% vs. 2.09%; Ohyper: 0.7% vs. 0.52%; and Shyper: 3.8% vs. 0.73%). Positive TPOAb, but not positive TgAb, was also associated with the prevalence of Shypo as diagnosed with the age-specific serum TSH reference range. Conclusion: The serum TSH level increases with age, which may represent a normal compensatory phenomenon in older adults ≥65 years. To prevent misdiagnosis and mistreatment, the use of an age-specific serum TSH reference range is recommended in older adults for the diagnosis of thyroid diseases.

Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro.

American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L. In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine.

This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB,8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: (a) quality control (QC) utilization, (b) validation of the lower reportable analytical limits, (c) units to be used in reporting measurable concentrations for patients and QC materials, (d) 99th percentile sex-specific upper reference limits to define the reference interval; (e) criteria required to define hs-cTn assays, (f) communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, (g) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, (h) harmonizing and standardizing assay results and the role of commutable materials, (i) time to reporting of results from sample receipt and sample collection, and (j) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections.

KEUNTUNGAN DAN KERUGIAN PENJAMINAN MUTU BERDASARKAN UJI MEMASTIKAN KECERMATAN (POCT)

Laboratory examination especially for critical care such as emergency care, intensive care has been developed near the site of patientcare which is referred to point-of-care testing (POCT). As to the definition of POCT, there are many synonyms such as ancillary testing,satellite testing, and bedside testing, near patient testing, home testing, self-management, patient self-management, remote testing andphysician's office laboratories. Based on evidence-based POCT, the National Academy of Clinical Biochemistry (NACB) has recommendedsome POCT such as coagulation tests, transcutan bilirubin testing, marker for acute coronary syndromes, diabetes mellitus, drugsand ethanol, Infectious disease testing, occult blood test, pH testing, renal function test, intraoperative PTH, renal function test andreproduction test. Some researchers conclude that performing POCT for critical care is efficient, while others found it not efficient,therefore, careful assessment of the advantages and disadvantages is important when implementing POCT. Nurses are the personnelin the acute care unit who often perform POCT; however they desire that laboratory personnel take the responsibility, therefore it isimportant to discuss which personnel are appropriate to conduct quality control of POCT.

Where does subclinical hypothyroidism start? Implications for the definition of the upper reference limit for thyroid stimulating hormone

The upper limit of the TSH reference range is currently under discussion. In its recent guidelines, the National Academy of Clinical Biochemistry (NACB) recommended the use of approximately 2.5 mIU/L, rather than approximately 4 mIU/L, due to the fact that reference populations, on which the definition of the reference range is based, contain persons undergoing an initial phase of autoimmune thyroid disease. This will skew the upper reference limit of TSH. Ultrasonography, in addition to measurement of thyroid autoantibodies, should be used to exclude these persons. The present study investigates whether the NACB recommendation also applies for a region of mild iodine deficiency. According to NACB criteria, a reference population (713 persons) was defined out of a total study population of 1442. The TSH reference range was calculated in this reference group and in further subgroups by percentiles. The results were compared with the total study population and the NACB recommendation. All assays used were provided by BRAHMS Diagnostica AG, Hennigsdorf, Germany. As expected, all median TSH values, excluding the median of the group with a hypoechogenic thyroid were close to 1.2 mIU/L. The 97.5th percentile in the reference population was 3.35 mIU/L. However, there was no difference compared to the total study population. The upper reference limit for TSH based on a reference population according to NACB criteria came down to 3.35 mIU/L, but not to approximately 2.5 mIU/L. Interestingly, there is no difference compared to the total study population.

Executive Summary: American Association of Clinical Chemistry Laboratory Medicine Practice Guideline-Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients.

The AACC Academy, formerly the National Academy of Clinical Biochemistry, has developed a laboratory medicine practice guideline (LMPG)10 for using laboratory tests to monitor drug therapy in pain management patients. The purpose of this guideline was to compile evidence-based recommendations for the use of laboratory and point-of-care (POC) urine drug tests for relevant over-the-counter medications, prescribed and nonprescribed drugs, and illicit substances in pain management patients. The exact process of preparing and publishing the LMPG is shown in Table 1. View this table: Table 1. Process of preparing and publishing a laboratory medicine practice guideline. Briefly, a multidisciplinary LMPG committee was established to include clinical laboratory professionals, clinicians practicing in pain management, and other relevant stakeholders, healthcare professionals, and clinical experts. The experts on the committee are listed in the guideline and represented the AACC Academy (L.J. Langman, P.J. Jannetto); Clinical and Laboratory Standards Institute, which is jointly preparing an expert opinion guideline on laboratory testing for pain management (C.A. Hammett-Stabler, L.J. Langman, G.A. McMillin); College of American Pathologists (S.E. Melanson); Evidence-Based Laboratory Medicine Committee (W.A. Clark); clinical laboratories performing pain management testing (L.J. Langman, P.J. Jannetto, C.A. Hammett-Stabler, G.A. McMillin, S.E. Melanson); AACC (C.A. Kassed); American Academy of Pain Medicine (T.J. Lamer, R.J. Hamill-Ruth, N. Bratanow); active pain management clinicians (T.J. Lamer, R.J. Hamill-Ruth, …

AACC Academy's Pain Management LMPG: Verification of Drug Dosing with Quantitative Urine Drug Testing?

Clinical practice guidelines have become a mainstay for streamlining medical practices and function to ensure uniformity. Clinical practice guidelines are relevant in the world of laboratory medicine, given the large number of medical decisions that are based on the result of a clinical laboratory test. The first set of guidelines was created in 1995 by the National Academy of Clinical Biochemistry (now the AACC Academy) and was called “Standards of Laboratory Practice.” The topic was the laboratory support of thyroid disease, and the guidelines were first published as a series of papers (1) and then widely distributed as a monograph. Later, guidelines were produced under the label “Laboratory Medicine Practice Guidelines” (LMPGs). In this issue of JALM , the Academy's latest LMPG addresses laboratory tests to monitor drug therapy in pain management patients (2). As an author of several other LMPGs, including one on laboratory tests to support cases of drug poisoning (3), a coauthor of a recently released toxicology guideline, the Clinical Laboratory Standards Institute Guideline on Toxicology and …