Progesterone, estradiol, and alpha-human chorionic gonadotropin secretion in patients with ectopic pregnancy

Plasma free alpha hCG, estradiol (E2), and progesterone (P4) concentrations were measured in 38 patients with histologically confirmed ectopic pregnancy (EP). The menstrual gestational ages ranged from 6-10 weeks. Free alpha hCG levels, although significantly lower than those in women with a normal intrauterine pregnancy, increased markedly during this time period, from 1.5 to 11 ng/ml, a 7-fold increase. In women with an intrauterine pregnancy, only 0.6-fold increase occurred during the same time period. Plasma P4 and E2 concentrations in patients with EP were significantly lower, except at 6 weeks for E2 and in the sixth and seventh weeks for P4. The ectopically implanted trophoblast undergoes impairment of its ability to synthesize beta hCG, but not alpha hCG. The lack of utilization of alpha hCG in EP causes it to increase, while the level of intact hCG is low. These observations suggest that the levels of alpha hCG are a sensitive marker for placental well-being, and that it could serve as an additional diagnostic tool for the early diagnosis of EP. The placenta is only partially able to compensate for the reduced ovarian production of E2 and P4.     

Monitoring of patients with non-seminomatous germ cell tumors of the testis by determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels and by computed tomography.

The results of a 7-year monitoring of 230 patients with non-seminomatous testicular tumors are reported with respect to the employment of radioimmunoanalysis of alpha-fetoprotein and beta-human chorionic gonadotropin levels and CT examinations of retroperitoneum and lungs. Prior to orchiectomy, elevated levels of at least one of these markers were found in 79% of patients. After orchiectomy, tumor marker levels were in 70.4% of patients in agreement with the results of CT examinations. After the completion of chemotherapy, in more than a half of patients normal tumor marker levels and positive CT findings were observed. These results were most often due to the presence of mature teratoma. In Stage I patients the advantages of tumor marker determinations and CT examinations in the early detection of tumor progression have fully been confirmed.     

Beta-core fragment is a major form of immunoreactive urinary chorionic gonadotropin in human pregnancy

A small mol wt fragment of the beta-subunit of hCG (beta-core fragment) is present in the urine, but not the serum, of pregnant women. We evaluated the relative proportions of this immunoreactive, but biologically inactive, fragment in urine from 15 women at different stages of pregnancy. Freshly voided urine was ultrafiltered and concentrated, and the molecular species of immunoreactive hCG were separated by Sephadex G-100 column chromatography. All urine samples contained the beta-core fragment, which eluted after the alpha-subunit of hCG. This fragment lacked the carboxy-terminal epitope of hCG, was inactive as an in vitro bioassay, and adsorbed to Concanavalin-A. The beta-core fragment was a major form the immunoreactive hCG in urine throughout pregnancy and accounted for over 90% of the immunoreactive hCG in urine from midpregnancy. The excretion pattern of the beta-core fragment can account for the low biological to immunological ratio of urinary hCG that occurs at different stages of pregnancy.     

Preintervention arterial remodeling as a predictor of intimal hyperplasia after intracoronary stenting: a serial intravascular ultrasound study.

BACKGROUND: The impact of vascular remodeling pattern on intimal hyperplasia (IH) after coronary stenting is unknown. HYPOTHESIS: The preintervention remodeling pattern of the lesion might be associated with IH after the coronary stenting procedure. METHODS: Serial (pre-, post-stent implantation, and follow-up) intravascular ultrasound (IVUS) images were obtained in 58 patients with single-stent implantation (GFX stents in 41 and NIR in 17). The matching IVUS image slices at the preintervention lesion site were selected for serial comparisons. The remodeling index (RI) was defined as lesion/proximal reference external elastic membrane cross-sectional area (CSA) at preintervention lesion site. Adequate remodeling was defined as a RI > 0.95 and inadequate remodeling as a RI < or = 0.95. Vessel stretching, percent vessel stretching, and percent IH CSA, as well as pre- and postintervention IVUS variables were evaluated according to the remodeling pattern. RESULTS: The percent IH CSA was 31% in adequate remodeling (n = 29, mean RI = 1.05) and 41% in inadequate remodeling (n = 29, mean RI = 0.88) (p = 0.049). Percent vessel stretching was 15% in adequate remodeling and 22% in inadequate remodeling (p = 0.007). The RI inversely correlated with percent vessel stretching (r = -0.435, p = 0.001). CONCLUSIONS: Compared with preintervention adequate remodeling, inadequate remodeling was associated with increased percent IH CSA, which might be related with more vessel stretching.     

Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma

Background—Human chorionic gonadotropin (hCG) isnormally produced and secreted by trophoblastic cells during pregnancyand from gestational trophoblastic neoplasms. It is also detected in ovarian, stomach, and colon adenocarcinomas, as well as in squamouscell carcinoma of the oesophagus. Recently, interest in its role in thepathogenesis of tumours has been enlivened after the presence of βhCGin the cell membrane of several malignant cells was shown in vitro.
Aims—To investigate the circulatingconcentrations of βhCG in patients with exocrine pancreaticadenocarcinoma and to examine its potential prognostic value.
Patients—Thirty six patients with exocrinepancreatic adenocarcinoma, 12 patients with chronic pancreatitis, and21 healthy volunteers were studied.
Methods—βhCG serum concentrations were detectedby the application of a radioimmunoassay technique.
Results—Fifteen of 36 patients with pancreaticadenocarcinoma and only one patient with chronic pancreatitis haddetectable plasma concentrations of βhCG (p<0.01). The patients withcirculating serum titres of βhCG had a worse outcome compared withthe group of βhCG negative patients: the difference was statisticallysignificant (p=0.01).
Conclusion—More than 40% of pancreatic exocrinetumours produce βhCG and its production is correlated with an adverseeffect on outcome.

Keywords:β-human chorionic gonadotropin; chorionicgonadotropin; pancreatic cancer; tumour marker; paraneoplasticsyndrome

     

Inhibition of implantation and termination of pregnancy in the rat by a human chorionic gonadotropin antagonist

Administration of varying doses (10-50 micrograms) of deglycosylated human CG (DG-hCG) which was previously shown to be a potent hormonal antagonist in vitro, to pregnant rats inhibited implantation and terminated gestation. When administered between days 1-5 implantation was inhibited as seen on day 10. Serum progesterone levels were also suppressed. Similar doses administered between days 8 and 11 resulted in complete fetal resorption when examined on day 16. This was also accompanied by a dramatic reduction in serum progesterone. A dose of 50 micrograms DG-hCG given during the second half of pregnancy between days 13 and 16 had no deleterious effect on pregnancy including the day of parturition but the number of pups delivered was reduced by 26% as compared to 3% loss in control groups. It is concluded that DG-hCG can successfully antagonize hormone action in vivo by blockade of ovarian receptor sites for LH in the pregnant rat.     

The origin of a human chorionic gonadotropin beta-subunit-core fragment excreted in the urine of patients with cancer

Immunoreactive human Chorionic Gonadotropin (hCG), its subunits and hCG beta-core fragment were analyzed, using Sephadex G-100 chromatography, in urine and tumour extracts from four patients with cancer. These patients were selected for investigation because they were excreting proportionally large amounts of the hCG beta-core fragment in their urine. Although 30-85% of the total immunoreactive urinary hCG was hCG beta fragment, traces of the fragment (2% of total hCG) were found in only two of the tumours and none in the other two. The predominant molecular form of hCG in the tumours was intact free beta-subunit of hCG. The conclusion is that the hCG beta-core fragment found in the urine of some patients with cancer is not a secretion product of the tumours. This fragment is very likely a peripheral degradation product of the free beta-subunit of hCG which is secreted by the tumours.     

Development of anti-human chorionic gonadotropin antibodies in patients with hypogonadotropic hypogonadism. A study of four patients

A young man with hypogonadotropic hypogonadism treated with hCG had resistance to this therapy and was found to have antibodies to hCG. We subsequently sought, using a sensitive radioimmunological method, anti-hCG antibodies in plasma from eight other hCG-treated children shown to have isolated hypogonadotropic hypogonadism. Antibodies to hCG were found in four of the nine. These antibodies were associated with the immunoglobulin fraction of plasma. In one patient antibodies were detected for 5 yr after therapy was discontinued. The titer and affinity constants of these antibodies were notably influenced by the therapeutic regimen used: the titer was significantly decreased and the affinity constant was lowered after reinstitution of therapy with larger hCG doses. In one patient the presence of anti-hCG antibody was associated with the failure to respond to hCG therapy.     

Estrogen mediates the protective effects of pregnancy and chorionic gonadotropin in a mouse model of vascular injury.

To determine why pregnancy protects against intimal proliferation in a mouse model of vessel injury, we administered chorionic gonadotropin to intact and ovariectomized female mice. Chorionic gonadotropin markedly suppressed intimal proliferation in intact but not in ovariectomized female mice, indicating that the protective effects of chorionic gonadotropin require ovarian function. To test whether estrogen or progesterone might mediate the protective effects of pregnancy and chorionic gonadotropin, we administered estrogen and progesterone to ovariectomized mice. Estrogen administration to ovariectomized mice to achieve the elevated levels seen in pregnancy was sufficient to reproduce the marked suppression of intimal proliferation in response to vessel injury. Progesterone administration reduced intimal proliferation to a lesser degree and was correlated with increases in estrogen to levels seen in nonpregnant female mice. Staining for proliferating cell nuclear antigen suggested that estrogen reduced medial and intimal cell proliferation. Both the classic estrogen receptor-alpha and the recently discovered estrogen receptor-beta are present in vascular tissue as assessed by immunohistochemistry, providing a possible mechanism for the effects of estrogen. These results suggest that the protective effects of estrogen do not plateau at levels seen in normal females but increase further with estrogen levels up through levels seen during pregnancy.     

Rate of bilirubin decrease as a risk predictor in hepato-biliary-pancreatic surgery.

BACKGROUND/AIMS: Although percutaneous transhepatic biliary drainage is widely performed for jaundice reduction, the clinical significance and mechanism responsible for delayed decrease of the bilirubin level remains unclarified. METHODOLOGY: The rate of bilirubin decrease was estimated in 104 consecutive patients who underwent drainage. Morbidity and mortality after major and minor operations for hepato-biliary-pancreatic diseases in groups showing slow and rapid bilirubin decrease were estimated. The risk factors for slow bilirubin decrease were also examined by uni- and multivariate analyses. RESULTS: A statistically significant difference between the slow and rapid bilirubin decrease groups was found only in the morbidity rates of major surgery (73% vs 28%, p < 0.05). Univariate analysis showed that the longer interval from onset of jaundice to drainage, the use of multiple catheters for jaundice reduction, and advanced age were significant risk factors for slow bilirubin decrease. These factors were found to be independent by multivariate analysis (p < 0.05) CONCLUSIONS: A slow rate of jaundice reduction is a predictor of high risk in major surgery. It can be attributed to 3 factors; longer term of undrained jaundice, multiple biliary drainage, and age. Careful post-operative management is required when major surgery is scheduled for patients with these risk-predictive factors.     

Hypothyroidism associated with anti-human chorionic gonadotropin antibodies secondarily produced by gonadotropin therapy in a case of idiopathic hypothalamic hypogonadism

We report a 22-yr-old male patient with idiopathic hypothalamic hypogonadism who showed secondary resistance to gonadotropin (Gn) therapy over 3 yr after successful treatment with hCG combined with human menopausal Gn. The patient simultaneously developed subclinical hypothyroidism. Endocrine examination revealed low levels of testosterone (0.3 ng/ml), free T4 (0.91 ng/dl), and increased levels of TSH (31.1 microU/ml) in the serum. Serum autoantibodies to thyroid gland were all negative. Interestingly, thyroid function was improved after discontinuation of Gn therapy. In vitro assays by immunoprecipitation using 125I-hCG or 125I-TSH elucidated the presence of anti-hCG antibody in the serum 13 months after commencement of Gn therapy but anti-TSH antibody was not detected in the serum. Furthermore, the anti-hCG antibody specifically bound to hCG but not to other glycoproteins including TSH and FSH based on a competitive displacement assay. Bioassays using porcine thyroid cells revealed that the serum gamma-globulin fraction enables the suppression of cyclic AMP (cAMP) synthesis stimulated by TSH. Our findings suggest that anti-hCG and/or anti-idiotypic hCG antibodies induced by hCG therapy impaired TSH-dependent cAMP production through interfering with binding of TSH to its receptor, and this resulted in subclinical hypothyroidism in this patient.     

Dietary pattern as a predictor of change in BMI z-score among girls

OBJECTIVES: To describe child and adolescent dietary patterns and to determine associations between childhood dietary pattern and longitudinal change in body mass index (BMI) z-score among girls. POPULATION AND METHODS: Healthy girls (n = 101) aged 8-12 years at baseline and 11-19 years at follow-up participated in a longitudinal study of growth and development. Participants kept 7-day dietary records at two points in time. We incorporated time of day, frequency, and amount of energy consumed (defined as percentage of total energy consumed per dietary event) when characterizing dietary patterns. RESULTS: Girls ate an average of 4-5 times per day and consumed most energy in the afternoon and in the evening/night, rather than in the morning. After controlling for baseline BMI, the mean percentage of daily energy consumed in the evening/night was positively associated with change in BMI z-score (P = 0.039). Eating between 4.0 and 5.9 times per day overall and no more than 1.9 times in the evening/night daily were negatively associated with change in BMI z-score (P = 0.002 and 0.047, respectively), after controlling for baseline BMI z-score. DISCUSSION: Recommendations to decrease the percentage of energy coming from the evening/night meal and the number of dietary events to no more than six times per day and two times in the evening/night should be evaluated in future longitudinal investigations.     

Serum levels of smooth muscle heavy-chain myosin in patients with ectopic pregnancy

STUDY OBJECTIVE: Previous studies have suggested that serum markers of smooth muscle destruction have utility in predicting ectopic pregnancy. Our goal was to determine whether a novel marker of muscle destruction, smooth muscle heavy-chain myosin (SMHC), is elevated in the serum of patients with ectopic pregnancy. METHODS: We conducted a prospective cohort study, with consecutive enrollment, of all women in the first trimester of pregnancy who presented to our urban emergency department with complaints of lower abdominal pain with or without vaginal bleeding. Patients were excluded if there was a history of recent surgery or major trauma. Means were compared using 2-tailed Student's t test with P values less than.05 set for significance. Data analysis included calculation of receiver operating characteristic (ROC), 95% confidence intervals (CIs), and a regression model. RESULTS: A total of 175 patients were enrolled; ectopic pregnancy was diagnosed in 29, and 146 had other diagnoses. Patients with ectopic pregnancy had a mean serum SMHC concentration of 2.53 ng/dL (95% CI 1.84 to 3.22), whereas those in the non-ectopic pregnancy group had a mean concentration of 1.41 ng/dL (95% CI 1.23 to 1.60; P <.0001). ROC analysis demonstrated an area under the curve of 0.72 (95% CI 0.65 to 0.79). Regression analysis to examine confounders in each group analyzed the effects of race, maternal age, estimated gestational age, and serum levels of human chorionic gonadotropin beta-subunit. Our analysis identified only a positive correlation between estimated gestational age and SMHC in the non-ectopic pregnancy group. CONCLUSION: There is a statistically significant elevation of serum SMHC levels in tubal pregnancy, although our data suggest that the assay has limited clinical utility as a lone marker for ectopic pregnancy. Further investigation is needed to determine whether the assay has a role as an adjunct in the evaluation of suspected ectopic pregnancy.     

Hyperthyroidism due to secretion of human chorionic gonadotropin in a patient with metastatic choriocarcinoma

A 26-year-old pregnant woman presenting with repeated episodes of vaginal bleeding, weight loss, and shortness of breath was diagnosed with choriocarcinoma with metastases to both lungs. Chorionic gonadotropin levels (hCG) were >2.5 x 10(6)mU/mL. Consistent with hCG-induced subclinical hyperthyroidism, she had a suppressed TSH of 0.037 mU/L (0.49 - 4.67), a T4 of 18.1 microg/dL (4.9 - 10.7), and T3 of 136 ng/dL (45 - 137). Chemotherapy with a combined regimen with etoposide, methotrexate, and dactinomycine was started. The initial course was complicated by urosepsis with respiratory distress requiring endotracheal intubation for 3 days. She then improved rapidly, and her thyroid function tests were within normal limits by day 12. Six months later, after ten cycles of chemotherapy, the patient was in remission without signs of residual tumor or hCG-induced paraneoplastic activity.