Reference Intervals for Plasma Amyloid β in Korean Adults Without Cognitive Impairment

Amyloid β (Aβ) peptides are important components of plaques in patients with Alzheimer's disease (AD). Recent studies suggest that a low plasma ratio of Aβ42 to Aβ40 may precede the development of the sporadic form of AD. The aim of this study was to establish reference intervals for plasma Aβ in Korean adults. A total of 370 apparently healthy individuals (181 males and 189 females aged 40-69 yr) without cognitive impairment were enrolled. Plasma concentrations of Aβ40 and Aβ42 were measured by using a human amyloid β assay kit (Immuno-Biological Laboratories, Japan). Reference intervals were established according to the "CLSI guidelines for defining, establishing, and verifying reference intervals in the clinical laboratory". There was no need to partition the data with respect to gender or age group. The 95th percentile reference intervals for Aβ40 and Aβ42 were 127-331 pg/mL and 2.31-19.84 pg/mL, respectively. The reference interval for the Aβ42/Aβ40 ratio was 0.011-0.092. Plasma Aβ concentrations obtained in this study could be used as reference intervals for clinical purposes.

Establishment of Trimester-Specific Reference Intervals for Thyroid Hormones in Korean Pregnant Women

BACKGROUND: Establishment of trimester- and assay-specific reference intervals for every population is recommended. The aim of this study was to establish a trimester- and assay-specific reference interval for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in Korean pregnant women. METHODS: From April 2012 to December 2012, 531 pregnant women receiving prenatal care and 238 age-matched, non-pregnant women were enrolled in this study. After excluding patients with pregnancy-associated complications or thyroid-specific autoantibody, 465 pregnant and 206 non-pregnant women were included. Non-parametric analysis (2.5-97.5th percentile) was performed to determine the reference interval. Levels of TSH and FT4 were determined by electrochemiluminescence immunoassay (Elecsys thyroid tests, Roche Diagnostics, Germany). RESULTS: The TSH reference intervals were 0.01-4.10, 0.01-4.26, and 0.15-4.57 mIU/L for the first, second, and third trimester, respectively. From the first trimester to the third trimester, the median TSH levels showed a significantly increasing trend (P<0.0001). The FT4 reference intervals were 0.83-1.65, 0.71-1.22, and 0.65-1.13 ng/dL for the first, second, and third trimester, respectively, showing a significantly decreasing trend (P<0.0001). CONCLUSIONS: Establishing trimester-specific reference intervals in pregnant women is essential for accurate assessment of thyroid function. Our population-specific and method-specific reference intervals will be useful for screening Korean pregnant women for thyroid disease.

HbA1c: A Review of Analytical and Clinical Aspects

After the relationship between glycemic control and the HbA1c concentration was demonstrated, many tests have been developed to determine the HbA1c concentration. The test results are standardized to the International Federation of Clinical Chemistry (IFCC) Reference Measurement Procedure (RMP) in harmony with the efforts of the National Glycohemoglobin Standardization Program (NGSP). The longitudinal use of the test requires strict quality management including accreditation of the laboratory, a dedicated internal control design, participation in an external quality assessment (EQA) program (proficiency test), and careful consideration of pre- and post-analytical aspects of the test. Performance goals for optimizing determination of the HbA1c concentration have been described. As an index of long-term glycemic control and a risk predictor, the HbA1c concentration is an indispensable part of routine management of diabetes. Because of the improving quality of the test, the HbA1c concentration is being increasingly applied in the diagnosis of diabetes. There are, however, concerns of this application in point-of-care settings. The HbA1c concentration is also used to achieve stringent control in pregnant diabetic patients. Strict standardization enables the definition of universal reference values and clinical decision limits. This review describes the present status of analytical and clinical aspects of determining the HbA1c concentration and highlights the challenges involved.

Does undetectable basal Tg measured with a highly sensitive assay in the absence of antibodies and combined with normal ultrasonography ensure the absence of disease in patients treated for thyroid carcinoma? / Tireoglobulina basal indetectável medida com ensaio ultrassensível na ausência de anticorpos e combinada com ultrassonografia normal assegura ausência de doença em pacientes tratados de câncer de tireoide?

It has been proposed that, in patients treated for well-differentiated thyroid carcinoma, undetectable basal thyroglobulin (Tg) levels measured with a highly sensitive assay in the absence of anti-thyroglobulin antibodies (TgAb) and combined with negative neck ultrasonography (US) ensured the absence of disease. We report a series of five patients with well-differentiated (papillary) carcinoma submitted to total thyroidectomy with apparently complete tumor resection, followed by remnant ablation with 131I (100-150 mCi), who had no distant metastases upon initial post-therapy whole-body scanning. When tumor recurrence or persistence was detected, these patients presented undetectable basal Tg (0.1 ng/mL) in the absence of TgAb, and US showed no anomalies. Two patients had lymph node metastases, one had mediastinal metastases, bone involvement was observed in one patient, and local recurrence in one. We conclude that further studies are needed to define in which patients undetectable basal Tg (negative TgAb) combined with negative US is sufficient, and no additional tests are required.

Tem sido proposto que em pacientes tratados de carcinoma bem diferenciado da tireoide o encontro de valores basais indetectáveis de tireoglobulina (Tg), dosada por ensaios ultrassensíveis, na ausência de anticorpos antitireoglobulina (TgAc), e combinado à ultrassonografia (US) cervical negativa, asseguraria ausência de doença. Reportamos aqui uma série de cinco pacientes com carcinoma bem diferenciado (papilífero), submetidos à tireoidectomia total, com ressecção tumoral aparentemente completa, seguida da ablação de remanescentes com 131I (100-150 mCi), sem metástases distantes na pesquisa de corpo inteiro pós-dose inicial, que, na ocasião em que a recorrência ou persistência tumoral foi detectada, apresentavam Tg basal indetectável (0.1 ng/ml), TgAc negativos e US sem anormalidades. Dois pacientes tinham metástases linfonodais, um tinha mediastinal, outro acometimento ósseo e um recorrência local. Concluímos que mais estudos são necessários para a definição de que pacientes com Tg basal indetectável (sem TgAc) combinada à US sem anormalidades seria suficiente, dispensando testes adicionais.

Troponina en el diagnóstico de infarto al miocardio: consideraciones desde el laboratorio clínico / Troponin in the diagnosis of myocardial infarction: an approach from the clinical laboratory

Among the many biomarkers studied to evaluate myocardial damage, troponin is considered the most sensitive and specific. However, current methodologies present pre-analytical, analytical and post-analytical problems, of which the more significant are the lack of standardization and a high uncertainty in the level of decision or cut-off. It is hoped that a new generation of assays called "ultra sensitive" will improve analytical performance characteristics of the technique and achieve compliance with the internationally recommended quality specifications.

Entre los múltiples biomarcadores estudiados para evaluar daño miocárdico, la troponina se considera el más sensible y específico. Sin embargo, la mayoría de las metodologías actuales utilizadas para su determinación presentan problemas tanto pre-analíticos, analíticos como post-analíticos, de los cuales los más relevantes son la falta de estandarización y una imprecisión alta en el nivel de decisión o de corte. Se espera que una nueva generación de ensayos para la determinación de troponina, denominados ultrasensibles, mejoren las características de desempeño de la técnica y logren cumplir con las especificaciones de calidad recomendadas internacionalmente.

Diagnóstico de la infección poe Helicobacter pylori en niños mediante la detección de antígenos en deposiciones / Diagnosis of Helicobacter pylori infection in children based on stool antigen test

Background: During infancy, preventive, diagnostic and therapeutic efforts for Helicobacter pylori infection should be made. Aim: To evaluate non-invasive diagnostic methods such as stool antigen test (HpSA) and serum anti-H pylori antibody detection (IgG e IgA), compared to endoscopy-based invasive methods (histology and urease test) for the diagnosis of Helicobacter pylori infection. Patients and Methods: Thirty nine children (aged 3 to 14 years, 20 males) referred for upper gastrointestinal endoscopy, were studied. The gold standard to diagnose Helicobacter pylori infection was defined as a positive invasive diagnostic test (histology and/or urease test). Sensitivity (S), specificity (E) and positive (PPV) and negative (NPV) predictive values were obtained for HpSA and serum antibodies. Results: Ten children (26 percent) were infected with H pylori. S, E, PPV and NPV for HpSA were 90, 100, 100 and 97 percent, respectively. The figures for serum IgG were 81, 97, 89 and 93 percent, respectively and for IgA, 90, 76, 36 and 96 percent, respectively. Conclusions: HpSA was sensitive and specific as a clinical and epidemiological tool to evaluate H pylori infection in children. Serology was not as accurate, but IgG had a better performance than IgA.

External quality assurance in diagnostic immunology: a twenty-year experience in Korea.

External Quality Assurance (EQA) Program in diagnostic immunology was founded in 1982 in Korea, starting from proficiency testing for HBsAg and serological tests for syphilis. Proficiency testing for antisteptolysin O (ASO) and Widal tests was started in 1983, rheumatoid factor (RF), C-reactive protein (CRP) and anti-HBs tests in 1986, anti-HIV in 1992, and anti-HCV in 1993, now assessing total nine immunological tests. EQA surverys are performed twice annually and about 400 laboratories have been participating now. Over 75% of participating laboratories have used immunoassays including enzyme immunoassay for HBsAg, anti-HBs, anti-HCV and anti-HIV, and less than 20% of laboratories used hemagglutination tests. Overall error rate for HBsAg was less than 5%, those for anti-HBs and anti-HCV about 3% and anti-HIV less than 0.5%. Only negative samples are now used for anti-HIV proficiency testing and two levels (negative and weakly positive or positive) of samples should be included in proficiency testing to assure the results. Thirty-five to forty-five percentages of participating laboratories have used nephelometry or turbidimetric immunoassay for CRP, RF and ASO. When comparing two kinds of nephelometry reagents most popularly used in Korea, quantitative results for CRP and RF by one kind were statistically different from the other. The reason for these discrepancies was not clear yet, however, standardization should be required. In the future, EQA in diagnostic immunology in Korea not only includes laboratory performance evaluation, but also evaluation of method performance and reagent evaluation.

The 'hook effect' on serum prolactin estimation in a patient with macroprolactinoma.

Large quantities of antigen in an immunoassay system impair antigen-antibody binding, resulting in low antigen determination. This is called the 'high dose hook effect'. We report this phenomenon in a patient with a large macroprolactinoma. In this patient, the correct estimate of serum prolactin (PRL) was obtained only after appropriate dilution of serum. We suggest that in order to avoid the high dose hook effect, the serum PRL be estimated in appropriate dilution in all patients with large pituitary tumours. This is particularly important when the clinical suspicion of high PRL is strong, as in women with amenorrhoea-galactorrhoea and men with long standing hypogonadism.