[Urinary gonadotropin fragment measurement in the monitoring of trophoblastic disease].

Urinary gonadotropin fragment (UGF) is a small peptide which is present in the urine of pregnant women and of women with trophoblastic diseases as well as with certain nontrophoblastic malignancies. 275 samples each of urine and blood from 46 patients with trophoblastic diseases were taken for UGF and hCG measurements and compared. 24 samples from 12 healthy, nonpregnant women were taken as control. Cut-off values of UGF and hCG used for measuring the sensitivity of trophoblastic diseases were respectively > 0.2 microgram/L and above 20 micrograms/L. It was found that 64.0% of the urine samples gave UGF values > 0.2 microgram/L and 66.5% of the blood samples showed hCG levels above 20 micrograms/L (P > 0.1). No false-positive rate was observed in the control group. However, among patients who were found to have low or negative hCG values, 57.6% showed positive UGF levels. These findings suggest that in patients with positive levels of both UGF and hCG, the UGF measurement may not be necessary. But for patients with low or negative blood hCG values, certain percentage of urine UGF could still be detected.

[Detection of hCG production in trophoblastic diseases by HCG beta carboxyl-terminal peptide].

A radioimmunoassay (CTP-RIA) for urinary human chorionic gonadotropin (hCG) with the use of an antiserum to be carboxyl-terminal peptide of hCG beta subunit was employed to detect hCG production in patients with gestational trophoblastic disease. In urine samples obtained from normal subjects, the upper limit of hCG-immunoactivity detected by this assay system was 1.1 IU/24h. More than 90% of the subjects tested had values lower than 0.5 IU/24h. Based on these data, we selected urinary hCG levels below 1.1 IU/24 h as the normal range for clinical applications. The utility of this new assay system was assessed in 50 cases of gestational trophoblastic disease. In patients with hydatidiform mole, invasive mole and undetermined cases, the urinary hCG level declined to be normal range following the therapy and stayed there afterwards without any sign of recurrence. However, in a woman with a long history of metastatic choriocarcinoma, we noted the reappearance of hCG even after the hCG level once declined to the normal range. It therefore seems that cell viability will persist even in the normal range determined by CTP-RIA. Therefore, therapeutic decisions should take into account these points. This specific and sensitive CTP-RIA method for the detection of hCG production was found to improve the ability to diagnose persistent or recurrent trophoblastic disease.

Dissociation of chorioadenoma destruens from hydatidiform mole by urinary steroid analysis.

Dissociation between hydatidiform mole (HM) and chorioadenoma destruens (CA) was attempted by gas chromatographic analysis of urinary steroids. In the chromatogram, fraction 2 (F2) including four pregnane steroids (17-hydroxypregnanolone, pregnanolone, pregnanediol, and pregnanetriol) reflected the biologic activity of molar human chorionic gonadotropin (hCG), and the ratio of F2 to fraction 1 (F1) (17-ketosteroids) was found useful in monitoring secondary growth of trophoblastic tumor: Urinary log F2/F1 after curettage declined quickly and unidirectionally in HM, but the same parameter exhibited a temporal rise in CA at 11 to 20 days after curettage because of the molar hCG from residual tumor tissue. The resolution between HM and CA at that stage (11 to 20 curettage days) was of the order of diagnostic use and superior to that with immunoreacive hCG. The data obtained are discussed in the light of pathophysiology of CA.

[The excretion of chorionic gonadetropin in 55 cases of hydatidiform mole (author's transl)]. / Die Ausscheidung von Choriongonadotropin bei 55 Fällen von Blasenmole

In 55 cases of hydatidiform mole, 323 quantitative assays of chorionic gonadotropin were evaluated. In cases of molar degeneration the mean HCG excretion was 20% below normal. In cases of hydatidiform mole and invasive mole the mean HCG excretion was significantly above normal. Many cases of hydatidiform mole and all cases of invasive mole showed a repeat rise of the HCG titres after curettage. The pattern of HCG excretion in hydatidiform mole is shown in diagrams.

The value of urinary steroid analysis in chorionic neoplasia.

The profile of urinary neutral steroids was investigated in normal pregnancy and chorionic neoplasia by gas-liquid chromatography. The whole chramatogram was divided into three metabolically distinct fractions. The excretion of fraction 2, including four menstruation-dependent steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetrial), was remarkably increased in normal pregnancy as compared with that in nonpregnant controls. But the same parameter was differentially reduced in hydatidiform mole (HM) and chorioadenoma destruens (CA) as compared with normal pregnancy, and the ratio of fraction 2 to fraction 1 (11-deoxy-17-ketosteroids) was found useful in separating normal pregnancy, HM, and CA from each other. In choriocarcinoma (CC), reduced excretion was observed in both fraction 1 and fraction 2 steroids. The linear relationship between the logarithm of fraction 2-fraction 1 ratio and that of pregnanediol excretion, as observed in the reproductive cycle of a healthy woman, was not detectable in women with CA, whose urine revealed a low value of log (fraction 2/fraction 1) in spite of an abundant HCG content. It is indicated that the above findings reflect the deficiency of ovarian steroidogenesis under the influence of abnormal HCG from tumors.

Hydatidiform mole metastasizing to the lung.

Pulmonary lesions developed in three patients with an invasive hydatidiform mole. At open thoracotomy the modules were found to contain molar tissue. Therapy with twice-weekly methotrexate induced complete clinical and biologic remission of the disease in all three patients.