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Determination of gestational age by serum concentrations of human chorionic gonadotropin.

To examine the accuracy and predictability of human chorionic gonadotropin concentrations in determining gestational age, serum concentrations of human chorionic gonadotropin (beta-subunit) were measured during the first 157 days after last menses. Using the regression curve generated, human chorionic gonadotropin concentrations obtained during the first 60 days accurately predicted the day of gestation. The difference (mean +/- SD) between the human chorionic gonadotropin-predicted estimated date of confinement and the estimated date of confinement established by known dates of last menses was 3.1 +/- 2.3 days. In patients followed to parturition, the difference between human chorionic gonadotropin-estimated gestational age and gestational age by physical assessment of the neonate was 8.1 +/- 7.1 days. After 60 days' gestation, human chorionic gonadotropin concentrations vary widely and are of little value in predicting gestational age. In addition to documenting conception, early human chorionic gonadotropin determinations accurately date the gestation and complement other clinical and biophysical methods for determining gestational age that are frequently used later in pregnancy.

Chorionic Gonadotropin↗

[Selective action of chorionic gonadotropin on lymphocyte subpopulations].

Influence of chorionic gonadotropin on induction and formation of specific T-suppressors, TDTH-effectors and spontaneous killer cells, depending on its doses and schema of injections was studied. It is shown that chorionic gonadotropin has a stimulating effect on precursors of T-suppressors, not affecting the mature specific T-suppressors, causes damage to the TDTH-effectors and spontaneous killer cells, that permits chorionic gonadotropin to be recognized as an immunomodulating agent.

Animals↗

The effects of various hormones on human chorionic gonadotropin production in early and late placental explant cultures.

Although human chorionic gonadotropin production peaks in early pregnancy, little is known of the factors regulating it at this time. We have compared human chorionic gonadotropin output in placental explants of 6 to 12 and 37 to 40 weeks' gestational age after addition of hormones on days 4 and 5 of 8 days of culture. Human chorionic gonadotropin production was sevenfold greater in early versus late cultures. In early cultures human chorionic gonadotropin output was increased threefold to fourfold by progesterone, dehydroepiandrosterone, and cortisol whereas late cultures responded only to progesterone and dehydroepiandrosterone. The output of combinations of steroids was additive or better (up to fifteenfold). Gonadotropin-releasing hormone increased human chorionic gonadotropin output only slightly (onefold to twofold) while testosterone was inhibitory (early) or ineffective (late). Estradiol had no effect. These studies demonstrate that explants of early placental tissue provide a useful model for study of human chorionic gonadotropin production, that there are many similarities but some clear differences between early and late secretion, and that steroids exert significant effects on human chorionic gonadotropin production of placental cultures.

Chorionic Gonadotropin↗

Second-trimester serum chorionic gonadotropin concentrations and complications and outcome of pregnancy.

BACKGROUND: Maternal serum chorionic gonadotropin is measured to screen for fetal chromosomal abnormalities. Whether the results can also be used to predict the risk of complications or an adverse outcome of pregnancy is not known. METHODS: We reviewed the medical records of 28,743 girls and women in whom chorionic gonadotropin was measured during the second trimester of pregnancy (between July 1, 1995, and January 31, 1997), seeking information about the complications and outcome of their pregnancies. We excluded girls and women who had preexisting risk factors for complications or an adverse outcome of pregnancy. RESULTS: Higher serum chorionic gonadotropin concentrations were associated with higher rates of stillbirth (odds ratio for every increase in chorionic gonadotropin of 1 multiple of the median, 1.4; 95 percent confidence interval, 1.1 to 1.9). There was no relation between higher serum chorionic gonadotropin concentrations and the risk of gestational diabetes, premature rupture of membranes or intrauterine growth retardation or small size for gestational age (odds ratio, 1.1; 95 percent confidence interval, 0.9 to 1.2). Higher serum chorionic gonadotropin concentrations were associated with a risk of placental abnormalities (odds ratio, 1.5; 95 percent confidence interval, 1.3 to 1.7), pregnancy-induced hypertension (odds ratio, 1.4; 95 percent confidence interval, 1.3 to 1.5), and preterm delivery without pregnancy-induced hypertension (odds ratio, 1.1; 95 percent confidence interval, 1.0 to 1.2). Inclusion in certain racial or ethnic categories (black, Filipino or Pacific Islander, unknown race or ethnic group, and "other," which included those of Middle Eastern descent and Native Americans) was a better predictor of the risk of an adverse outcome than serum chorionic gonadotropin values. CONCLUSIONS: Measurements of serum chorionic gonadotropin are of little clinical value for predicting the risk of complications and the outcome of pregnancy.

Adolescent↗

Ectopic production of the beta-subunit of human chorionic gonadotropin in osteosarcoma.

Production of human chorionic gonadotropin by sarcomas is an uncommon phenomenon that has rarely been documented. A case of a 26-year-old woman with osteosarcoma of the left fibula and high levels of serum beta-human chorionic gonadotropin (beta-HCG) is described. Immunoperoxidase staining showed numerous tumor cells reacting with the beta-HCG antibody. Immunohistochemical studies performed on ten additional osteosarcomas demonstrated another case in which some tumor cells presented immunoreactivity for beta-HCG. These results indicate that beta-HCG may be used as a marker of persistent or recurrent disease in those uncommon cases of osteosarcoma in which serum levels of beta-HCG are elevated at the onset of treatment.

Adult↗

Cerebrospinal fluid human chorionic gonadotropin levels in normal pregnancy and choriocarcinoma.

We measured human chorionic gonadotropin levels simultaneously in the serum and cerebrospinal fluid of 36 normal pregnant women and of six patients with choriocarcinoma. During normal pregnancy, human chorionic gonadotropin levels in the cerebral spinal fluid correlated well with those in the serum in both the first and third trimesters. A serum-cerebral spinal fluid human chorionic gonadotropin ratio of less than 60 has previously been reported as a sensitive diagnostic test for trophoblastic central nervous system involvement. However, we found this ratio to be less than 60 in one patient undergoing first trimester abortion and in one patient with nonmetastatic choriocarcinoma. Furthermore, two patients with documented trophoblastic cerebral metastases had serum-cerebral spinal fluid human chorionic gonadotropin ratios in excess of 60. Results of our study, thus, indicate that determination of a single serum-cerebral spinal fluid human chorionic gonadotropin ratio may not conclusively prove or exclude trophoblastic central nervous system metastases. Unless it is corroborated by other diagnostic means, a single decreased serum-cerebral spinal fluid human chorionic gonadotropin ratio is insufficient evidence to initiate multimodality treatment for presumptive central nervous system involvement.

Brain Neoplasms↗

Antigenic similarities to HCG subunits among chorionic gonadotropins of nonhuman primates.

Comparison of antigenic similarity between human chorionic gonadotropin (HCG) subunits and the chorionic gonadotropins of six species of nonhuman primates indicates marked similarity of antigenic determinants between both subunits of HCG and the chorionic gonadotropins of chimpanzees, gorillas, and orangutans. Antisera to HCG subunits (alpha or beta) did not cross-react with the chorionic gonadotropins of baboons, macaques, or marmosets. Because of the relative availability of chimpanzees for laboratory studies, we suggest that chimpanzees may be the optimal nonhuman primate model for determining the advisability of vaccinations in man using conjugates of HCG fragments to achieve fertility control or for suppression of HCG-producing neoplasms.

Animals↗

The free beta-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma.

The free beta-subunit of human chorionic gonadotropin beta is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human chorionic gonadotropin beta expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin beta in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin beta in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin beta, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin beta were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin beta levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l(-1), P=0.0029). In multivariate analysis human chorionic gonadotropin beta, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin beta is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin beta in serum may be used to identify patents with increased risk of progressive disease.

Adult↗

Selecting human chorionic gonadotropin immunoassays: consideration of cross-reacting molecules in first-trimester pregnancy serum and urine.

OBJECTIVE: We investigated the variation in human chorionic gonadotropin results found with different commercial kits. Levels of human chorionic gonadotropin and related molecules were determined in pregnancy serum and urine and compared with the specificities of different laboratory, office, and home test kits. STUDY DESIGN: Total human chorionic gonadotropin (nicked+nonnicked), nonnicked human chorionic gonadotropin, free beta subunit, and beta core fragment were measured in 242 serum samples and 125 urine samples from early pregnancies. RESULTS: In serum, in the 2 weeks after the missed period when most pregnancy tests are performed, median levels of total, nonnicked, and beta human chorionic gonadotropin (total+free beta+beta core) were similar (< or = 12% difference). Individual values, however, varied significantly. For nonnicked human chorionic gonadotropin, values ranged from 41% to 145% and for beta from 101% to 145% of the total human chorionic gonadotropin level. In urine individual nonnicked values varied from < 1% to 148% and beta values from 102% to 547% of the total human chorionic gonadotropin level. A survey of 29 kits revealed that 10 were types detecting total human chorionic gonadotropin, five detecting nonnicked only, and 14 were beta assays. CONCLUSIONS: Results from total, nonnicked, and beta human chorionic gonadotropin kits are not necessarily interconvertible. Individual variations in levels of nicked human chorionic gonadotropin, free beta and beta core, and differences in their recognition by immunoassays causes discordant results.

Chorionic Gonadotropin↗

Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty.

To elucidate whether the cause of sexual maturation arrest in thalassaemia is of gonadal or pituitary etiology, 10 males with thalassaemia and delayed puberty and 10 with constitutional delay of growth and pubertal maturation (CSS) were extensively studied. Their spontaneous nocturnal gonadotropin secretion and gonadotropin response to intravenous 100 micrograms gonadotropin-releasing hormone (GnRH) were evaluated. Circulating testosterone concentration and clinical response were evaluated after 3 days, 4 weeks and 6 months of intramuscular administration of human chorionic gonadotropin (HCG) (2500 U/m2/dose). Thalassaemic boys had significantly lower circulating concentrations of testosterone compared to those with constitutional delay of growth and sexual maturation (CSS) at the same pubertal stage. Short- and long-term testosterone response to administrations of HCG was markedly decreased in thalassaemic boys. After 6 months of HCG administration 50 per cent (5/10) of the boys did not show significant testicular enlargement or genital changes. Despite the low circulating concentrations of testosterone, none of the patients had high basal or exaggerated gonadotropin response to gonadotropin releasing hormone (GnRH) stimulation. Luteinizing hormone (LH) peak responses to GnRH were significantly lower as compared to controls. Follicle-stimulating hormone (FSH) peak responses to GnRH did not differ among the two study groups. The mean nocturnal LH and FSH secretion was significantly decreased in all thalassaemic boys as compared to boys with CSS at the same pubertal stage (testicular volume). These data proved that hypogonadotropic hypogonadism is the main cause of delayed/failed puberty in adolescents with thalassaemia major. MRI studies revealed complete empty sella (n = 5), marked diminution of the pituitary size (n = 5), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 8) in thalassaemic patients, denoting a high incidence of structural abnormalities (atrophy) of the pituitary gland. Moreover, in many of the thalassaemic boys, the defective testosterone response to long-term (6 months) HCG therapy denoted significant testicular atrophy and/or failure secondary to siderosis. It appears that testosterone replacement might be superior to HCG therapy in these patients. This therapy should be introduced at the proper time in these hypogonadal patients to induce their sexual development and to support their linear growth spurt and bone mineral accretion.

Adolescent↗

The effect of low-dose aspirin on pregnancies complicated by elevated human chorionic gonadotropin levels.

OBJECTIVE: Our purpose was to determine whether elevated second-trimester human chorionic gonadotropin levels identify women likely to benefit from low-dose aspirin therapy. STUDY DESIGN: We evaluated second-trimester human chorionic gonadotropin levels obtained from healthy nulliparous women before screening for participation in a double-blind randomized trial of aspirin therapy: 262 women took 60 mg of aspirin daily and 420 did not. RESULTS: Among women who did not take aspirin, those with human chorionic gonadotropin levels > or = 2.0 multiples of the median had a significantly lower mean birth weight (2859 vs 3159 gm, p = 0.04) than did those with normal human chorionic gonadotropin levels. All women who took aspirin had a higher mean birth weight than women who did not, but women with human chorionic gonadotropin levels > or = 2.0 multiples of the median had the greatest increase (416.2 gm higher in those with human chorionic gonadotropin levels > or = 2.0 multiples of the median, p = 0.02; 96 gm higher in those with human chorionic gonadotropin levels > or 2.0 multiples of the median, p = 0.04). Regression analysis suggested that the higher birth weight was partly explained by a higher gestational age at delivery and partly by increased weight independent of gestational age. CONCLUSIONS: Aspirin therapy increased birth weight in all women, especially in women with high human chorionic gonadotropin levels, partly by increasing gestational age at delivery. This observation needs to be confirmed by further studies.

Adolescent↗

Human chorionic gonadotropin detected in urinary concentrates from patients with malignant tumors of the testis, prostate, bladder, ureter and kidney.

Human chorionic gonadotropin levels in concentrated 24-hour urine and serum were determined by a specific radioimmunoassay of beta-human chorionic gonadotropin in 47 patients with genitourinary carcinoma. Elevated human chorionic gonadotropin levels in urine were observed in 6 of 8 patients with active testicular tumor, 3 of 14 with prostatic cancer, 2 of 10 with bladder cancer, 1 of 2 with ureteral or renal pelvic tumors and 2 of 6 with renal cancer. Of the 14 patients with positive urinary human chorionic gonadotropin 4 had undetectable human chorionic gonadotropin levels in the serum. The tumors of all 8 patients with nontesticular cancer who had increased urinary human chorionic gonadotropin levels were in an advanced clinical stage or of poor histological differentiation. Our results suggest that some nontrophoblastic carcinomas of the genitourinary system are capable of ectopic production of human chorionic gonadotropin, particularly if the malignancy is advanced or poorly differentiated. The radioimmunoassay of beta-human chorionic gonadotropin in concentrated 24-hour urine specimens enhances the sensitivity of detection of ectopic human chorionic gonadotropin production.

Aged↗

Doubling times of human chorionic gonadotropin increase in early viable intrauterine pregnancies.

Although the doubling time of serum human chorionic gonadotropin has been assumed to be constant in early viable intrauterine pregnancy (prior to 6 to 7 weeks after menses), the range has varied between 1.4 and 3.5 days in the literature. To evaluate this variability of the doubling time, the mean doubling times at different ranges of human chorionic gonadotropin concentrations were determined in 49 normal pregnancies, and the doubling times at different intervals of gestation from both the day of the basal body temperature shift and the last menstrual period. The data obtained from the three different methods indicate that the doubling time of human chorionic gonadotropin is not constant but rather increases with increasing human chorionic gonadotropin concentration or gestational age. In addition, statistical analysis of the semilogarithmic plots of serum human chorionic gonadotropin concentrations indicated that the exponential rate of increase of serum human chorionic gonadotropin significantly decreases with gestational age. Since serum human chorionic gonadotropin doubling times increase and the exponential rate decreases with gestational age, estimates of normal values should be established for small sampling ranges and/or short intervals of gestation.

Chorionic Gonadotropin↗

Prospective evaluation of maternal serum human chorionic gonadotropin levels in 3428 pregnancies.

As part of a multicenter prospective study, second-trimester human chorionic gonadotropin and alpha-fetoprotein concentrations were evaluated. Data included maternal age, human chorionic gonadotropin level, alpha-fetoprotein level, weight, race, and pregnancy outcome of 3428 pregnancies at between 15 and 20 weeks' gestation. The results of the study indicate that human chorionic gonadotropin levels decrease as maternal weight increases, that weight-adjusted human chorionic gonadotropin levels for Oriental and black women are higher than for white or Hispanic women, and that twin pregnancies have higher human chorionic gonadotropin levels than singleton pregnancies. Of 255 pregnancies that did not have normal outcomes, 54 (21.2%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median and 26 (10.2%) had alpha-fetoprotein levels greater than 2.5 multiples of the median. Of 11 pregnancies with fetal aneuploidy, 6 (54.5%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median. It is concluded that in human chorionic gonadotropin screening programs for fetal Down syndrome, weight and race adjustments are necessary for accurate risk assessment.

Aneuploidy↗

Elevated beta-human chorionic gonadotropin and a search for cancer.

Elevated human chorionic gonadotropin levels may be an early, and occasionally the only, manifestation of embryonal cell carcinoma. A 24-year-old man presented with gynecomastia, galactorrhea, and elevated beta-human chorionic gonadotropin levels, which led to an extensive (but nonrevealing) search, including computed tomography and selective testicular vein catheterization, for malignancy. Since the testicle was considered as the most likely site of tumor, right orchiectomy and right common iliac lymph node biopsy were performed. The testicle was normal, but the lymph node contained elements of embryonal and choriocarcinoma. Following chemotherapy, beta-human chorionic gonadotropin levels were normalized and the patient appears "cured." This case emphasizes the need for an extensive search for malignancy and consideration of orchiectomy in such instances in order to achieve a favorable outcome.

Adult↗

Immunocytochemical discordance in localization of pregnancy specific beta-1 glycoprotein, alpha-fetoprotein and human chorionic gonadotropin in testicular cancers.

Immunocytochemical discordance of human chorionic gonadotropin, alpha-fetoprotein and pregnancy specific beta-1 glycoprotein was studied in formaldehyde-fixed tissues of 26 patients with germinal testicular cancer. The cellular localization of these 3 markers has been correlated with the serum markers in the 26 patients. Serum alpha-fetoprotein, human chorionic gonadotropin and specific beta-1 glycoprotein were elevated in 15 of 26 (58 per cent), 17 of 26 (65 per cent) and 7 of 26 (27 per cent) patients, respectively, and in 22 of 26 (85 per cent) when all markers were considered. The cellular alpha-fetoprotein was localized in 5 of 26 (19 per cent), human chorionic gonadotropin in 12 of 26 (46 per cent) and specific beta-1 glycoprotein in 9 of 26 (35 per cent) patients. When all the markers were considered 15 of 26 patients (58 per cent) had either alpha-fetoprotein, human chorionic gonadotropin or specific beta-1 glycoprotein localized in the cancer cells.

Choriocarcinoma↗