Discordant Results in Human Chorionic Gonadotropin Assays

1992 ◽  
Vol 38 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Laurence A Cole ◽  
Andrew Kardana
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Terminal Segment ◽  
Beta Subunit ◽  
Alpha Subunit ◽  
Individual Sample ◽  
Serum Samples ◽  
Subunit C ◽  
Core Fragment ◽  
Alpha Type

Abstract 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.

Free α-Subunit, Free β-Subunit of Human Chorionic Gonadotropin (hCG), and Intact hCG in Sera of Healthy Individuals and Testicular Cancer Patients

1992 ◽  
Vol 38 (3) ◽  
pp. 370-376 ◽  
Author(s):  
S Madersbacher ◽  
R Klieber ◽  
K Mann ◽  
C Marth ◽  
M Tabarelli ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Beta Subunit ◽  
Alpha Subunit ◽  
Serum Concentrations ◽  
Healthy Individuals ◽  
Pathological Conditions

Abstract To determine the serum concentrations of human chorionic gonadotropin (hCG), its free beta-subunit (hCG beta), and the free alpha-subunit (free alpha) common to all human glycoprotein hormones under physiological and pathological conditions, we developed monoclonal antibody-based immunoenzymometric assays. Free alpha-subunit was detected in the sera of all healthy individuals of both sexes; hCG was measurable in sera of 54% of the men, and 46% were positive for free hCG beta; in nonpregnant women, 69.5% were positive for hCG, 68.4% for the free beta-subunit. Pathological conditions, i.e., hCG-producing tumors, were studied in vitro and in vivo. In vitro, the concentrations of hCG, free hCG beta, and free alpha in tissue-culture supernates of a choriocarcinoma cell-line ("JAR") showed a parallel pattern during time-course analysis. In vivo, in long-term follow-up studies of 13 patients with testicular cancer, serum concentrations of the three analytes paralleled each other, whether the disease was in remission or not. Because of a selective increase of free hCG beta and free alpha in 27% of seminomatous tumor patients and in 13% of the nonseminomatous patients, the percentage of tumor-marker-positive sera was increased from 15% to 42% and 57% to 70%, respectively, by the additional measurement of free hCG beta and free alpha. Thus hCG, free hCG beta, and free alpha are physiologically present in a high percentage of the sera from healthy men, and the determination of free hCG beta and free alpha, although not of prognostic value, improves the diagnostic possibilities in patients with testicular cancer.

scholarly journals Ability of human chorionic gonadotropin β-subunit to inhibit the steroidogenic response to lutropin

1979 ◽  
Vol 180 (3) ◽  
pp. 573-578 ◽  
Author(s):  
R R Dighe ◽  
K Muralidhar ◽  
N R Moudgal
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Beta Subunit ◽  
Alpha Subunit ◽  
Immature Rat ◽  
Progesterone Production ◽  
Pregnant Mare Serum Gonadotropin ◽  
Serum Gonadotropin ◽  
Constant Dose ◽  
Human Chorionic Gonadotropin Beta

Ability of the beta-subunit of human chorionic gonadotropin to inhibit the response to lutropin (luteinizing hormone, LH) was tested in the immature rat ovarian system and pregnant-mare-serum-gonadotropin-primed rat ovarian system with progesterone production being used as the response. Human chorionic gonadotropin beta-subunit was found to inhibit human and ovine lutropin-stimulated progesterone production. At a constant dose of lutropin, inhibition was dependent on the concentration of beta-subunit. When concentration of the beta-subunit was kept constant at 5.0 microgram/ml and the concentration of lutropin was varied, the inhibition was maximum at the saturating concentration of the native hormone. The alpha-subunit of the human chorionic gonadotropin did not inhibit the response to lutropin. The lutropin/beta-subunit ratio required to produce an inhibition of response was much lower than that required to bring about an observable inhibition of binding.

scholarly journals Substantial urinary concentrations of material resembling beta-core fragment of chorionic gonadotropin beta-subunit in mid-menstrual cycle

1993 ◽  
Vol 39 (9) ◽  
pp. 1857-1860 ◽  
Author(s):  
P Neven ◽  
R K Iles ◽  
I Howes ◽  
K Sharma ◽  
J H Shepherd ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Luteinizing Hormone ◽  
Tumor Marker ◽  
Molecular Mass ◽  
Chorionic Gonadotropin ◽  
Beta Subunit ◽  
Alpha Subunit ◽  
Core Fragment ◽  
Prolonged Excretion

Abstract We measured the day-to-day variations in concentrations of beta-core, luteinizing hormone (LH), and alpha-subunit in urine during the menstrual cycle. The alpha-subunit concentrations showed a pattern similar to that of the LH concentrations. beta-Core-like material was increased during and up to 3 to 4 days after the surge in urine LH. The urine LH concentration was associated with the presence of beta-core immunoreactivity during the urine LH peak. Chromatography showed that, at the peak LH concentration and at 2 days after the LH peak, beta-core immunoreactivity could be accounted for by the presence of a peptide of low molecular mass similar to the beta-core molecule of hCG, but probably originating from the degradation of LH. The prolonged excretion of gonadotropin metabolites in the midcycle must be considered when beta-core is being assessed as a tumor marker.

Simultaneous assay of alpha-fetoprotein and free beta subunit of human chorionic gonadotropin by dual-label time-resolved immunofluorometric assay

1993 ◽  
Vol 39 (10) ◽  
pp. 2084-2089 ◽  
Author(s):  
K Pettersson ◽  
H Alfthan ◽  
U H Stenman ◽  
U Turpeinen ◽  
M Suonpää ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Alpha Fetoprotein ◽  
Beta Subunit ◽  
Published Data ◽  
Freezing And Thawing ◽  
Serum Samples ◽  
Time Resolved ◽  
Repeated Freezing ◽  
Dual Label

Abstract We developed a simple, rapid two-step dual-label assay for the noncompetitive determination of alpha-fetoprotein (AFP) and beta subunit of human chorionic gonadotropin (hCG beta) in serum. Monoclonal antibodies to detect AFP and hCG beta were labeled with europium (Eu) and samarium (Sm), respectively. Highly fluorescent chelates were developed by using the Delfia enhancement principle. The detection limits for AFP and hCG beta were approximately 0.02 kIU/L and approximately 0.2 IU/L, respectively. The within-run precision was < 5% over the whole range of AFP (1-500 kIU/L) and hCG beta (1-200 IU/L) concentrations tested. Cross-reaction of intact hCG was < 0.03%. The AFP concentrations determined with the dual-label assay correlated well with those obtained by Delfia AFP single-label kit. The concentrations of hCG beta were in good agreement with recently published data. Storing the serum samples for 24 h or 1 week at room temperature increased the hCG beta concentration by 4% and 26%, respectively. At 35 degrees C this dissociation of hCG increased 30-40-fold. Repeated freezing and thawing had no effect on the hCG beta concentration.

scholarly journals Falsely Decreased Human Chorionic Gonadotropin (hCG) Results Due to Increased Concentrations of the Free β Subunit and the β Core Fragment in Quantitative hCG Assays

2010 ◽  
Vol 56 (12) ◽  
pp. 1839-1844 ◽  
Author(s):  
David G Grenache ◽  
Dina N Greene ◽  
Anand S Dighe ◽  
Corinne R Fantz ◽  
Daniel Hoefner ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
False Negative ◽  
Normal Pregnancy ◽  
Serum Samples ◽  
Core Fragment ◽  
Negative Results ◽  
Fixed Concentration ◽  
False Negative Results ◽  
High Concentrations

BACKGROUND Earlier studies have shown that increased concentrations of certain human chorionic gonadotropin (hCG) variants can cause false-negative results in some qualitative hCG devices. The objective of this study was to determine if increased concentrations of hCGβ and hCGβ core fragment (hCGβcf) cause falsely decreased results on 9 commercially available quantitative hCG assays. METHODS Several concentrations of purified hCGβ and hCGβcf were added to 2 sets of 6 serum samples with and without a fixed concentration of intact hCG. We examined 9 widely used immunoassays to measure immunoreactive hCG. Falsely decreased results were defined as those in which the measured hCG concentration was ≤50% of expected. RESULTS High concentrations of hCGβ (≥240 000 pmol/L) produced falsely decreased hCG measurements in 2 assays known to detect this variant. Similarly, high concentrations of hCGβcf (≥63 000 pmol/L) produced falsely decreased hCG measurements in 3 assays that do not detect purified hCGβcf. Two assays were identified that detected both hCGβ and hCGβcf, and neither produced falsely decreased results in the presence of high concentrations of these variants. CONCLUSIONS Extremely high concentrations of hCG variants can cause falsely decreased results in certain quantitative hCG assays. Of the 9 assays examined, none exhibited falsely decreased results in the presence of hCGβ concentrations typically associated with hCGβ-producing malignancies. Two assays exhibited decreased (>50%) hCG results in the presence of hCGβcf concentrations found during normal pregnancy.

Human Chorionic Gonadotropin and CA 15-3 Producing Adenocarcinoma

1998 ◽  
Vol 37 (08) ◽  
pp. 297-298 ◽  
Author(s):  
A. Özet ◽  
A. Arpaci ◽  
S. Kömiircü ◽  
G. Üçkaya
Keyword(s):  
Lung Adenocarcinoma ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Carbohydrate Antigen ◽  
Beta Subunit ◽  
Cancer Antigen ◽  
First Report ◽  
Primary Lung Adenocarcinoma ◽  
Adenocarcinoma Of Lung

Summary50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (βHCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although βHCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

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