Total hCG tests

IntroductionThere are 12 types of automated total hCG tests sold today, the Abbott Architect, Abbott AxSym, the Beckman Access 2. Beckman DxI 800, the Ortho Vitros EciQ, Roche Elecsys hCG + β, Siemens ACS180, Siemens Centaur, Siemens Dimension, Siemens Immulite and Siemens Stratus, and the Tosoh A1A. All tests claim to be total hCG tests but do not define what total means. Total hCG test needs to detect all hCG variants in order to be used for all hCG test clinical applications. Here we assess this ability.MethodsCoded samples of pure hCG, nicked hCG, hyperglycosylated hCG, nicked hCG missing C-terminal peptide, nicked hyperglycosylated hCG, asialo hCG, hCGβ, nicked hCGβ and β-core fragment were tested blindly in serum and urine at 10 independent laboratories.ResultsWhile the Siemens Immulite total hCG test detected 8 of 9 hCG variant standards, other assays poorly detected important determinants such as nicked hCG missing the C-terminal peptide, β-core fragment, hyperglycosylated hCG, nicked hCG, asialo hCG, and hCGβ. Four assay appropriately detected 4 of 9 variants, 2 assays detected 3 of 9, 4 assays detected 2 of 9 and 1 assay only appropriately detected 1 of 7 hCG variants.DiscussionCare is needed in selecting a total hCG test. The Siemens Immulite tests performed best at detecting all the hCG variants making it appropriate for all applications. Nine assays had limited applications, 3 of the assays were appropriate for advanced pregnancy testing only.     

Quantitative, wide-range, 5-minute point-of-care immunoassay for total human chorionic gonadotropin in whole blood

BACKGROUND: Human chorionic gonadotropin (hCG) is among the most common analytes available for point-of-care immunotesting, with most assays currently based on simple manual assay devices. However, as the importance of good analytical performance of rapid assays is increasingly emphasized, more sophisticated immunoassay techniques are needed to meet the future challenges of rapid yet quantitative POC testing. METHODS: We developed a simple, dry-reagent, all-in-one immunoassay for the quantitative measurement of hCG in whole blood, plasma, or serum. The noncompetitive assay equally measures intact, nicked, and hyperglycosylated hCG as well as nonnicked and nicked hCG beta-subunit with a rapid and simple procedure consisting of a 5-min, one-step incubation and, subsequent to washing, the measurement of time-resolved fluorescence directly from a wet well surface. RESULTS: The assay had a detection limit (background + 3 SD) of 0.4 IU/L hCG. The within-run CV was <15% down to 2 IU/L, and the assay was linear to 6000 IU/L. The within- and between-run CVs in heparinized whole blood and plasma were 相似文献   

Utility of commonly used commercial human chorionic gonadotropin immunoassays in the diagnosis and management of trophoblastic diseases

BACKGROUND: Patients with trophoblastic diseases produce ordinary and irregular forms of human chorionic gonadotropin (hCG; e.g., nicked hCG, hCG missing the beta-subunit C-terminal segment, hyperglycosylated hCG, and free beta subunit) that are recognized to differing extents by automated immunometric hCG (or hCG beta) assays. This has led to low or false-negative results and misdiagnosis of persistent disease. False-positive hCG immunoreactivity has also been detected, leading to needless therapy for trophoblastic diseases. Here we compare seven commonly used hCG assays. METHODS: Standards for five irregular forms hCG produced in trophoblastic diseases, serum samples from 59 patients with confirmed trophoblastic diseases, and serum samples from 12 women with previous false-positive hCG results (primarily in the Abbott AxSYM assay) were blindly tested by commercial laboratories in the Beckman Access hCG beta, the Abbott AxSYM hCG beta, the Chiron ACS:180 hCG beta, the Baxter Stratus hCG test, the DPC Immulite hCG test, the Serono MAIAclone hCG beta tests, and in the hCG beta RIA. RESULTS: Only the RIA and the DPC appropriately detected the five irregular hCG standards. Only the Beckman, DPC, and Abbott assays gave results similar to the RIA in the patients with confirmed trophoblastic diseases (values within 25% of RIA in 49, 49, and 54 of 59 patients, respectively). For samples that were previously found to produce false-positive hCG results, no false-positive results were detected with the DPC and Chiron tests (5 samples, median <2 IU/L), but up to one-third of samples were false positive (>10 IU/L) in the Beckman (1 of 5), Serono (2 of 9), and Baxter assays (1 of 5), and the hCG beta RIA (3 of 9; median for all assays, <5 IU/L). These samples, which produced false-positive results earlier in the Abbott AxSYM assay, continued to produce high values upon reassessment (median, 81 IU/L). CONCLUSIONS: Of six frequently used hCG immunometric assays, only the DPC detected the five irregular forms of beta hCG, agreed with the RIA, and avoided false-positive results in the samples tested. This assay, and similarly designed assays not tested here, seem appropriate for hCG testing in the diagnosis and management of trophoblastic diseases.     

The analytical specificity of human chorionic gonadotropin assays determined using WHO International Reference Reagents

BackgroundHuman chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with considerable molecular heterogeneity. There is uncertainty regarding which hCG variants are detected by different hCG assays. The analytical specificity of 8 hCG assays was investigated.MethodsWHO International Reference Reagents for hCG, nicked hCG (hCGn), beta subunit (hCGβ), nicked beta subunit (hCGβn), and beta core fragment (hCGβcf) were individually added to hCG-free human serum. Specimens were analyzed with 8 commercially available hCG assays. Equimolar detection of hCG variants was defined as a recovery of 90–110%.ResultsAll assays detected hCG and hCGn with mean recoveries of 98.3 and 94.6%, respectively. Seven assays detected hCGβ (mean recovery 103.8%) but with high variation, and equimolar detection was observed only in four. The mean recovery of hCGβn was 85.5% but was highly variable with only two assays showing equimolar detection. With a mean recovery of 53.4%, two assays detected hCGβcf and both underestimated it considerably. Information provided by the assay manufacturer regarding hCG variant analytical specificity was inadequate or unclear in 75% of the assays.ConclusionshCG assays vary considerably in their ability to detect different hCG variants. Manufacturers of hCG assays should clearly indicate the hCG variant specificity of their reagent systems.     

The hCG assay or pregnancy test

This review examines human chorionic gonadotropin (hCG) or pregnancy tests from multiple perspectives. It first investigates the molecule hCG and shows that the term represents five independent molecules differing in carbohydrate and meric structure that share a common amino acid sequence. The review goes on to show that multiple degradation produces also the need to be tested for an hCG or pregnancy test to be optimally efficient. The review then carefully examines the literature showing the sensitivity and specificity of automated laboratory tests. Point-of-care pregnancy tests are then investigated along with over-the-counter pregnancy tests. Appropriate detection of hyperglycosylated hCG, nicked hCG, nicked hCG missing the β-subunit C-terminal peptide and nicked hyperglycosylated hCG is a limitation on all pregnancy tests. In the opinion of the author, just one automated laboratory test, the Siemen’s Immulite, one point-of-care test, the Beckman-Coulter Icon 25, and one brand of over-the-counter device, First Response, are suitable for early pregnancy detection and possibly other applications.     

Detection of early pregnancy forms of human chorionic gonadotropin by home pregnancy test devices.

BACKGROUND: Home pregnancy testing devices claim >99% diagnostic accuracy for pregnancy and utility on the first day of the missed menses or earlier. We investigated the forms of human chorionic gonadotropin (hCG) in early pregnancy urines, the diagnostic accuracy claim, and the abilities of 15 devices to detect the different forms of hCG. METHODS: We measured the concentrations of regular hCG and hyperglycosylated hCG (H-hCG, a large hCG variant) in 592 urines. Fifteen home devices were tested according to manufacturers' instructions with regular hCG and H-hCG diluted in urine. RESULTS: H-hCG was the principal hCG-related molecule in pregnancy urine in the 2 weeks following the missed menses (61% and 50% of total immunoreactivity in the 4th and 5th completed weeks of pregnancy, respectively). Of 15 home test devices, 2 had a detection limit of 6.3 IU/L for regular hCG, but poorer detection of H-hCG. Two devices detected 13 IU/L regular hCG, one with similar detection and one with poorer detection of H-hCG. Ten devices detected 25 IU/L regular hCG, 6 with poorer detection of H-hCG. One device detected 50 IU/L regular hCG, but better detected H-hCG. Overall, 9 of 15 devices did not detect H-hCG as well as regular hCG. CONCLUSIONS: H-hCG is the principal hCG immunoreactivity in early pregnancy urine. Home tests vary widely in detection limits for regular hCG (6.3-50 IU/L), and 9 of 15 devices (60%) had poorer detection limits for H-hCG than for hCG. The variation in analytical detection limits appears contradictory to the common claim for all devices of >99% detection of pregnancy on the first day of the missed menses or earlier. We suggest that manufacturers calibrate devices for both hCG and H-hCG and determine the detection rates for pregnancy rather than the proportion of positive results at arbitrary hCG concentrations.     

Human chorionic gonadotropin in pregnancy diagnostics

Human chorionic gonadotropin (hCG) is a 237 aminoacid glycoprotein hormone composed of two dissimilar α and β subunits noncovalently linked by charge interactions, which are both required for the biological activity of the hormone. Due to structural heterogeneity, hCG exists in biological fluids as a mixture of different isoforms, i.e., intact active hormone (hCG), nicked hCG (hCGn), free β subunits (hCGβ), free α subunit (hCGα), β-core fragment (hCGβcf, predominantly detected in urine and containing amino acids 6-40 and 55-92 linked by disulphide bridges) and nicked free β-subunit (hCGβn). Although the measurement of hCG might be useful in a kaleidoscope of clinical conditions, such as diagnosis, monitoring and follow-up of pregnancy-related disorders, prenatal screening and gynecological cancers, the leading application is still the diagnosis of pregnancy, where it can be measured quantitatively either in serum or urine, in the latter case also using qualitative and rapid immunoassays. Since there is still debate as to whether serum or urine tests are to be preferred for establishing a diagnosis of pregnancy, we discuss here the main analytical and clinical aspects of hCG measurement for the diagnosis of pregnancy, highlighting the advantages and limitations of assessing hCG in urine and serum.     

Hyperglycosylated hCG (invasive trophoblast antigen, ITA) a key antigen for early pregnancy detection

OBJECTIVES: Hyperglycosylated human chorionic gonadotrophin (hCG) is an hCG variant with extra-large O-linked oligosaccharides, produced by phenotypically invasive cytotrophoblast cells in choriocarcinoma and pregnancy. It is the principal form of hCG produced in the first weeks of gestation. We investigated the importance of hyperglycosylated hCG in pregnancy testing and its detection by current hCG tests. DESIGN AND METHODS: We measured the concentration of hyperglycosylated hCG and total hCG in 512 pregnancies throughout gestation. We assessed and compared the abilities of 14 commonly used commercial laboratory hCG tests and 18 home pregnancy tests to detect regular and hyperglycosylated hCG. RESULTS: Hyperglycosylated hCG is the principal source of hCG-related immunoreactivity in early pregnancy. In the week following missing menses, hyperglycosylated hCG measurements may be more sensitive than regular hCG measurements in detecting pregnancy. Of 14 commercial laboratory hCG tests, 3 appropriately detected hyperglycosylated hCG standard. Of 18 different home pregnancy products 11 poorly or very poorly detected this key antigen. CONCLUSIONS: Hyperglycosylated hCG may be the key molecule in the detection of early pregnancy. However, the majority of tests poorly detected or failed to detect this key antigen. New pregnancy tests are needed that either solely detect hyperglycosylated hCG or equally detect regular hCG and hyperglycosylated hCG.     

Discordant results in human chorionic gonadotropin assays.

Discordance has been reported in human chorionic gonadotropin (hCG) concentrations measured by different immunoassay kits. We examined the results for 40 serum samples assayed with 10 different hCG immunoassay kits. Results varied considerably. Individual sample results varied by as much as 58-fold. Average results for different kits varied by as much as 1.4-fold for pregnancy (20 samples) and 2.2-fold for trophoblast disease (20 samples) serum. We investigated the causes of this discordance. hCG or hCG beta are general names for mixtures of hCG, hCG alpha, or hCG beta immunoreactive molecules in serum. These mixtures include regular hCG, nicked hCG (missing peptide linkages at beta 44-45 or beta 47-48), carbohydrate variants of hCG, hCG missing the beta-subunit C-terminal segment, free beta-subunit, beta-core fragment, and free alpha-subunit. We prepared standards for each of these major variants and measured their reactivities in the 10 hCG immunoassay kits. Free beta-subunit reactivity varied from nonrecognition (anti-beta:anti-alpha type kits; Hybritech Tandem-R and others) to overrecognition (one kit had five-fold greater affinity for free beta than for hCG). Kits with antibodies to beta-subunit C-terminal segment (Organon NML and others) failed to recognize hCG missing this segment, a component of serum hCG in trophoblast disease. Kits with anti-hCG antibodies (Serono MAIA-clone and others) had minimal recognition of nicked hCG (12%), a component of all serum hCG samples, and consistently gave the lowest values with all serum samples. We conclude that differences in recognition of nicked hCG, free beta, and these other hCG variants cause discordance in hCG immunoassay results.     

Preparation and characterization of new WHO reference reagents for human chorionic gonadotropin and metabolites

BACKGROUND: The currently used standards for human chorionic gonadotropin (hCG) and its alpha and beta subunits (hCGalpha and hCGbeta) contain substantial amounts of contaminating variants of hCG and other impurities. Furthermore, some partially degraded forms of hCG and its subunits have become of potential clinical importance, e.g., "nicked" forms of hCG (hCGn) and hCGbeta (hCGbetan), which contain cuts in the peptide backbone between amino acids 44-45 or 47-48 in hCGbeta, and a fragment of hCGbeta (hCGbetacf) consisting of amino acids 6-40 and 55-92 bound together by disulfide bridges. The IFCC appointed a working group with the aim of preparing new standards for hCG and related substances to improve standardization of their immunoassays. METHODS: Large amounts of hCG and its subunits as well as of hCGn, hCGbetan, and hCGbetacf were prepared by previously developed purification methods in combination with hydrophobic interaction chromatography and reversed-phase HPLC. Each preparation was characterized on the basis of amino acid and sequence analyses, carbohydrate composition, and electrophoretic patterns. Immunoassays for relevant contaminating proteins were also performed. RESULTS: The major preparations were homogeneous and free of contaminating proteins. Concentrations of the final preparations were determined by amino acid analysis. CONCLUSIONS: Calibrated in substance concentrations (mol/L) based on amino acid analyses, these preparations will facilitate improved standardization of immunoassays for hCG and its metabolites. The six preparations have now been established by the WHO as new 1st Reference Reagents for immunoassays with the following codes: hCG 99/688, hCGbeta 99/650, hCGalpha 99/720, hCGn 99/642, hCGbetan 99/692, and hCGbetacf 99/708. In contrast to the 3rd International Standard (75/537), the clinically most important Reference Reagent for hCG (99/688) contains no hCGn and negligible amounts of free subunits.     

Charge variants in serum and urine hCG

BACKGROUND: All serum and urine pregnancy tests sold in the United States are calibrated against the WHO 3rd and 4th International Standards (3rd and 4th I.S.) of Human Chorionic Gonadotropin (hCG). These standards have been isolated from pregnancy urine; however, they are used to calibrate, and generate antibodies used in both urine and serum hCG tests. hCG molecules may vary in sialic acid content; this changes the acidity of the molecule. Published studies have shown that these carbohydrate elements may alter recognition of hCG in different serum and urine hCG tests. We investigated the charge variants of hCG in serum and urine samples, and in hCG standards. METHODS: Samples were analyzed by preparative isoelectric focusing. Charge variants of hCG were quantitated using the DPC Immulite hCG assay. RESULTS: A difference was observed in the proportion of charge variants in urine and serum samples. There was a significantly higher proportion of more-acidic variants in the urine samples. CONCLUSIONS: Urine-derived standards may not be representative of serum hCG and therefore may not be appropriate for calibrating serum assays. Variation among hCG test results when using different immunoassays has been a persistent problem for years. Additional studies are needed to focus on the molecular dissimilarity of urine and serum hCG, as well as other factors, to determine their significance and contribution to the problem of interassay variation when comparing hCG results.     

Standardization of two immunoassays for human glandular kallikrein 2

BACKGROUND: Measurement of human kallikrein 2 (hK2) has improved early detection and staging of prostate cancer. However, reported concentrations of hK2 among currently used assays have not been standardized in any way. We compared two hK2 assays and five different recombinant hK2 variants (rhK2) and suggest a common calibrator as an important step and putative reference substance in hK2 assay standardization. METHODS: We measured 146 sera by two hK2 assays, using assay-specific calibrators to assess the difference between the two assays. Serial dilutions of five rhK2 preparations were measured repeatedly, with one preparation assigned as calibrator and the others as unknowns to define which variant provided the closest match between the two assays. This rhK2 variant was used to recalibrate both assays. We measured hK2 concentrations in the same 146 patients to evaluate the change in the difference. RESULTS: Use of assay-specific calibrators for comparison of the two assays yielded a Deming regression equation of: y = 0.789 (95% confidence interval, 0.674-0.922)x + 0.014 (0.004-0.025) micro g/L; R(2) = 0.667. Analysis of five rhK2 variants revealed that the enterokinase (ek)-rhK2 form provided the best match between both assays. Using the ek-rhK2 as a common calibrator, we observed a change in the slope of the regression curve to: y = 1.106 (0.872-1.340)x + 0.006 (-0.002 to 0.016) micro g/L; R(2) = 0.648, suggesting an increase in the mean estimate of agreement between the two assays. CONCLUSION: Calibration with a common calibrator substantially increased agreement between the assays. The ek-rhK2 variant provided the best performance of all tested rhK2 variants and should undergo mass spectrometry and amino acid analysis for exact mass determination and value assignment to evaluate its potential as a reference material for immunoassays for hK2.     

Comparison of two assays measuring human chorionic gonadotrophin serum concentrations in pregnancy termination and trophoblastic or non-trophoblastic tumours

Background: Differences in human chorionic gonadotrophin (hCG) results provided by the commercial immunoassays reflect the heterogeneity of antibodies and the use of suboptimal standards. As a consequence, the principal forms of hCG and metabolites are differentially detected and the hCG tests are not suited for the same clinical applications. Conflicting results are available in the literature regarding which hCG variants are recognized by the Roche Elecsys hCG?+?β test. The aim of our study was to compare the hCG concentrations provided by the Siemens Immulite 2000 test and the Roche test as well as to assess the concordance between both assays.

Methods: In this purpose, 152 samples obtained from women and 44 samples from men were analysed by both tests during the follow-up of pregnancy termination, gestational trophoblastic disease and malignancies. The intermediate precision of the Roche test was also investigated on a pool with a low hCG concentration.

Results and conclusions: The hCG concentrations measured with the Roche test were slightly lower compared with the Siemens assay; mean biases of ?34.2% and ?8% were respectively obtained for hCG values ≤100?UI/L and higher than 100?UI/L. The overall agreement between both assays was 96.1% for women and 97.7% for men. By using an upper reference limit of 3.2?UI/L for women and 1.6 UI/L for men, the Roche test demonstrated a respective concordance of 98.7% and 100%. This test also yielded an excellent precision with a coefficient of variation of 2.8% at a mean hCG concentration of 7?UI/L.     

Establishment, value assignment, and characterization of new WHO reference reagents for six molecular forms of human chorionic gonadotropin

BACKGROUND: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group to investigate means of improving the comparability of immunoassays for human chorionic gonadotropin (hCG), which was selected as a prototype glycoprotein analyte. The Working Group identified development of unambiguous nomenclature and production of new highly purified International Reference Reagents calibrated in substance concentrations as its primary objectives. METHODS: Preparations of intact hCG, nicked hCG, hCG beta-subunit, nicked hCG beta-subunit, hCG alpha-subunit, and hCG beta-core fragment were purified from a crude urinary hCG preparation, ampouled, lyophilized, and assigned values in substance concentrations (mol/L). Value assignment and accelerated degradation studies were carried out in accordance with WHO protocols for International Reference Reagents. RESULTS: The ampouled standards were assigned final values based on the recovery of immunoreactive material after reconstitution. The degradation studies showed that the standards were highly stable. CONCLUSIONS: The nomenclature of hCG-related molecules and immunoassays has been adopted by the IFCC, and the standards prepared and characterized by the Working Group have been formally adopted by the WHO as the First International Reference Reagents for six hCG-related molecules. These developments will enable better understanding of what assays for hCG measure and should ultimately help to improve the clinical application of these assays.     

Diagnostic considerations in the measurement of human chorionic gonadotropin in aging women

BACKGROUND: Human chorionic gondadotropin (hCG) screening tests are performed on nearly all female patients of childbearing age before any medical intervention. Although older women usually have negative hCG test results, positive results do occur and may cause clinical confusion. We examined changes with age in serum hCG concentrations in nonpregnant women and investigated the use of serum follicle-stimulating hormone (FSH) measurements as an aid to interpreting higher than expected ("positive") hCG results. METHODS: We used 240 serum specimens for each of 4 female cohorts: pregnant, > or =18 years; nonpregnant, 18-40 years (premenopausal); nonpregnant, 41-55 years (perimenopausal); and nonpregnant, >55 years (postmenopausal). Patients were excluded if they had an ectopic pregnancy, a history of trophoblastic disease or a germ-cell tumor, or if no chart was available for review. Quantitative hCG and FSH tests were performed on each specimen. RESULTS: Serum hCG concentrations in nonpregnant women increased with the age of the women. hCG results were higher and significantly different (P < 0.0001) for nonpregnant women >55 years (<2.0 to 13.1 IU/L) compared with nonpregnant women 18-40 years (<2.0 to 4.6 IU/L) and 41-55 years (<2.0 to 7.7 IU/L). Nineteen nonpregnant women >40 years of age had hCG concentrations > or = 5.0 IU/L, all with an FSH concentration >32.4 IU/L. The highest FSH concentration in pregnancy was 7.3 IU/L. CONCLUSIONS: Serum hCG increases with age in nonpregnant women. A cutoff of 14.0 IU/L should be used when interpreting hCG results in women >55 years of age. Pregnancy is unlikely in perimenopausal women 41-55 years of age with an hCG between 5.0 and 14.0 IU/L if serum FSH is >20.0 IU/L.     

hCG, five independent molecules

INTRODUCTION: The hCG amino acid sequence supports 5 glycoproteins. All are called hCG forms. This review examines all 5 molecules, the hormone as produced by the placental syncytiotrophoblast cells, the sulfated hormone produced by the pituitary gonadotrope cells, the hyperglycosylated hCG autocrine made by placental cytotrophoblast cells, and the autocrine cancer promoters hyperglycosylated hCG, hCG? and hyperglycosylated hCG? as made by all malignancies. This review examines all the molecules and multiple proven functions, ranging from evolution to cancer promotion to hormone action. RESULTS AND DISCUSSION: hCG forms are critical super-growth factors in humans, with an exceptional wide range of functions.     

False positive immunometric assays caused by anti-immunoglobulin antibodies: a case report

A serological phenomenon causing aberrant results with monoclonal immunoenzymetric assays (IEMA's) is reported. Two different commercial IEMA kits detected low levels of choriogonadotropin (hCG) in the serum of a non-pregnant woman. These assays detected between 32 and 55 IU/l of serum hCG over a 3-wk period; however, an RIA for beta-subunit and two monoclonal immunoradiometric assays (IRMA's) detected no hCG (less than 5 IU/l). An IEMA measurement of creatine kinase MB isozyme was also elevated. Antisera to either human immunoglobulin or specifically to human IgM, added to the serum prior to assay, substantially decreased these IEMA reactions. Addition of either mouse serum or purified mouse IgG totally abolished them. It is concluded that these spurious reactions were most likely caused by an IgM antibody which binds to native and enzyme-labelled mouse IgG, but not to iodinated IgG.     

Use of serum FSH to identify perimenopausal women with pituitary hCG

BACKGROUND: Human chorionic gonadotropin (hCG) tests are performed on many female patients before performing medical procedures or administering medications that may harm a fetus. hCG of pituitary origin has been shown to increase with age. Therefore, mild increases in serum hCG in an older patient can be of pituitary origin and does not necessarily indicate pregnancy. The inability to rule out pregnancy in perimenopausal women can create clinical confusion and may delay needed therapies. Our objective was to determine the diagnostic utility of serum follicle-stimulating hormone (FSH) concentrations to rule out hCG of placental origin in perimenopausal women with a low concentration of serum hCG (5.0-14.0 IU/L). METHODS: Seven testing centers performed 39 742 physician-ordered serum quantitative hCG tests over a 15-month period. From these, 100 samples from women 41-55 years of age with serum hCG concentrations 5-14 IU/L were identified. We performed FSH testing and patient chart review for each sample. RESULTS: Twenty-three patients were found to have hCG of placental origin (pregnancy, resolving abortion, or gestational trophoblastic disease), and in those cases serum FSH was 0.4-43.8 IU/L. An FSH cutoff of 45.0 IU/L identified hCG of placental origin with 100% sensitivity and 75% specificity. FSH >45 IU/L was never observed when hCG was of placental origin (negative predictive value). CONCLUSIONS: These data indicate that quantitative serum FSH can be used to rule out pregnancy and hCG of placental origin in women 41-55 years of age with mild increase in serum hCG concentrations.     

Retrospective evaluation of 99th percentile hCG results to adjust clinical decision points

While accurate measurement of chorionic gonadotropin (hCG) is necessary, so are appropriate clinical decision points (CDPs) for patients of all ages. The CDP for hCG is intended to identify early pregnancy in patients of child bearing age; non-pregnant patients who are older frequently yield hCG results > 5 IU/L, making the use of a low hCG CDP problematic for these patients. Using a retrospective review of all hCG results generated over a 32-month period, 8507 hCG results from non-pregnant females of all ages were analyzed. Patients < 40 years of age comprised 74% of hCG measurements, and produced hCG results ≥ 5 IU/L 1% of the time, but this frequency increased in patients 40–49 (17% of hCG results; 4% ≥5 IU/L) and ≥50 (9% of hCG results; 20% ≥ 5 IU/L). While only 3% of hCG results were ≥5 IU/L in the overall data set, all (24/24) of hCG results 10–14 IU/L came from patients ≥ 40 years of age and all (3/3) hCG results ≥ 15 IU/L came from patients ≥ 50 years of age. The 99th percentile hCG results in the population were 3 IU/L in patients < 40, 7 IU/L in patients 40–49, and 13 IU/L in patients ≥ 50 years of age. These findings demonstrate a progressive increase in measurable hCG correlating to patient age and demonstrate a proof-of-concept that institutions could assess 99th percentile hCG results to assign more appropriate method-dependent CDPs to different age groups.     

Determination of lipase catalytic activity in two reference materials: BCR 693 and BCR 694 by titrimetry at constant pH.

Because routine assays for pancreatic lipase catalytic activity are not yet standardized, between-method comparability is very poor. This is mainly due to the lack of reference materials (RMs). The aim of this study was to assign values of catalytic concentration to two human pancreatic lipase RMs, one prepared from human pancreatic juice (BCR 693), the other obtained by recombinant technology (BCR 694). Lipase catalytic activity was assayed in five experienced laboratories, using aliquots from the same lot of triolein emulsion and a standardized titrimetric procedure, optimized with regard to substrate, cofactors and pH. The accepted sets of data (n = 4) gave a mean +/- the corresponding uncertainty expressed as the 0.95 confidence interval of 1732 +/- 72 U/l and 1043 +/- 60 U/l for BCR 693 and 694, respectively. Transferability of the whole operating procedure proved to be quite satisfactory. The authors conclude that both RMs can be used to verify the correct implementation of the standardized measurement procedure and to assign values to secondary lipase materials (commercial calibrators, control products) which, in turn, ensures traceability to the standardized procedure in this study, and contributes to the harmonization of laboratory results according to the Directive for in vitro Diagnostic Medical Devices.