Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ ...cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing hormone and testosterone values are normally low.
We measured the number of spermatogonia per tubule at orchiopexy in 72 consecutive boys with cryptorchidism who underwent simultaneous testicular biopsy. In 19 patients gonadotropin releasing hormone was unsuccessful, while 8 received HCG and 45 underwent orchiopexy without hormonal therapy. Groups were otherwise equal.
Patients who underwent surgery only had a higher number of spermatogonia per tubule than those in whom hormonal treatment was unsuccessful (p <0.05). Spermatogonia per tubule values were normal only after surgery alone (p = 0.06). Gonadotropin releasing hormone and HCG influenced germ cells equally.
In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells.
The USA hCG Reference Service is a consulting service with a specialized clinical laboratory aiding physicians in the interpretation of conflicting or nonrepresentative human chorionic gonadotropin ...(hCG) results. We have consulted on 189 cases with persistent low levels of hCG but no evidence of pregnancy or tumor. Quiescent gestational trophoblastic disease (GTD) was identified in 121 cases by the absence of invasive trophoblast antigen and nonresponse to chemotherapy (64 cases with a history of hydatidiform mole or gestational trophoblastic neoplasia (GTN) and 57 cases following antecedent pregnancy). Another 61 Reference Service cases hadfalse positive hCG, and we observed 7 cases with low levels of hCG of pituitary origin (hCG subsequently suppressed by estrogen-progesterone medication). Most disturbing is that the majority of these cases (68%) received needless therapy for assumed GTN/choriocarcinoma/placental site trophoblastic tumor before consultation with the Reference Service. One hundred twenty-eight of the 189 patients (77 of 121 with quiescent GTD, 48 of 61 withfalse positive hCG and 3 of 7 with pituitary hCG) underwent therapy ranging from single-agent chemotherapy (117 cases), to EMA-CO combination chemotherapy (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and vincristine) (16 cases), to hysterectomy and/or bilateral salpingo-oophorectomy (31 cases). False positive hCG and pituitary hCG would obviously not respond to these treatments, and no treated cases of quiescent GTD responded to chemotherapy orfully responded to hysterectomy. The continued needless treatment of patients with quiescent GTD, even after multiple publications, is entirely avoidable. Unfortunately, the number of needlessly treated cases referred to the Reference Service is increasing.
Human chorionic gonadotropin (hCG) is a glycoprotein composed of 2 dissimilar subunits, alpha and beta, joined non-covalently. This hormone is not only heterogeneous in peptide structure but also in ...combination of subunits and in the structure of carbohydrate side chains. Common hCG-related molecules in serum samples include regular hCG, hyperglycosylated hCG (ITA), nicked hCG, nicked ITA, hCG missing the beta-subunit C-terminal extension, free alpha-subunit, free beta-subunit, free beta-subunit missing the C-terminal extension, hyperglycosylatedfree beta-subunit and nickedfree beta-subunit. The same molecules plus beta-core fragment are present in urine samples. While ITA and regular hCG predominate in pregnancy samples, any one of these multiple hCG-related molecules may be the principal source of immunoreactivity in gestational trophoblastic disease, gestational trophoblastic neoplasm, choriocarcinoma and placental site tumor cases as well as in testicular cancer and germ cell tumor. As such it is critical to appropriately detect all these isoforms in the management of these diseases. Only 2 tests, the DPC Immulite (DPC, Inc., Los Angeles, California) and U.K. RIA (radioimmunoassay) (used at Charing Cross Hospital, London) appropriately detect all these hCG-related molecules. False positive hCG results are a major problem in the management of gestational trophoblastic disease and cancer. A particular problem is observed with the Abbott AxSym test. This test is flawed in design. It should be avoided in the management of gestational trophoblastic disease and cancer. As shown in a blind study, a proportion of false positive samples in the Abbott AxSym test (Abbott Laboratories, Inc., Chicago, Illinois) can also be false positive with the U.K. RIA; none are false positive with the DPC Immulite test. Results clearly show that the DPC Immulite/Immulite 2000 is the only appropriate assay for monitoring patients with gestational trophoblastic disease or cancer.
Human chorionic gonadotropin (HCG) has a stimulatory effect on testicular steroidogenesis and has been widely used for evaluating male Leydig cell function. However, considerable variability exists ...in the protocols for HCG stimulation tests. In the most commonly used protocols HCG is administered daily for several days. We examine the circulating androgen response after 1 and 3-dose HCG regimens.
We evaluated 77 prepubertal boys diagnosed with hypospadias, cryptorchidism or micropenis. In 60 boys who underwent 1 dose of 100 IU/kg. or 5,000 IU/1.7 m.
2 HCG serum testosterone and dihydrotestosterone were sampled at 72 (28) and 96 (32) hours after injection, while in 17 who underwent 3 daily age adjusted doses hormone levels were determined on day 4. All blood specimens were obtained and injections were performed at 8:00 to 9:00 a.m. and all specimens were evaluated at the same endocrine reference laboratory.
Nonstimulated testosterone levels were prepubertal in all groups. In the 1-dose groups post-stimulation testosterone was elevated 22 to 29-fold from baseline after a weight based and 34 to 35-fold after a body surface area based dose. Testosterone increased 20-fold baseline in the multi-dose group. No significant differences were observed in 72 versus 96-hour hormone levels.
Evaluating Leydig cell function by HCG stimulation is an important adjunct to the diagnosis of various urological conditions. A single weight or body surface area based HCG dose with androgen measurement after 3 or 4 days is a practical, reliable and cost saving change in testicular evaluation.
We determined whether human chorionic gonadotropin (HCG) pretreatment of severe proximal penoscrotal hypospadias and chordee causes sufficient penile shaft or skin enlargement to enhance surgical ...repair and improve patient outcome.
A total of 12 boys 6 to 12 months old with proximal hypospadias and severe chordee received a course of HCG for 5 weeks immediately preceding hypospadias repair.
Chordee decreased and penile length increased in all cases (mean increase 94%). Penile length gain was disproportional. Most of the increase in length was proximal to the urethral meatus, which moved the meatus distally an average of 11.4 mm. (range 6.0 to 19.0), producing a mean increase of 586% in the distance between the penoscrotal junction and meatus. In contrast, there was no statistically significant increase in penile shaft length distal to the urethral meatus. Surgical treatment was facilitated by HCG pretreatment. Three meatal based repairs were performed, only 1 urethral fistula developed and chordee was corrected by penile degloving only in 8 cases.
HCG pretreatment in infancy produces disproportional penile enlargement, which advances the meatus distally to decrease the severity of hypospadias and chordee. This response pattern simplifies the required surgical procedure and appears to improve surgical results. It may benefit select patients, and provide insights into the endocrinopathy of hypospadias and the embryopathy of the hypospadias-chordee complex.
Because of contradictory reports of pregnancy outcomes and coffee intake, this study was designed to determine how hormone metabolite levels, symptoms, and coffee consumption patterns are related. ...Eligible subjects were recruited in Cincinnati, Ohio, from 1996 to 1998, aged 18–40 years, and nonsmokers; drank at least 18 ounces (1 ounce = 29.6 ml) of coffee per week (including decaffeinated) at the last menstrual period; and were enrolled by 9 weeks from the last menstrual period. Beverage consumption and pregnancy symptoms were recorded daily. Weekly, first-morning urine samples were collected to assess human chorionic gonadotropin, estrone-3-glucuronide, and pregnanediol-3-glucuronide. A time-dependent, repeated measures analysis was performed to test several associations. Data from 92 subjects were analyzed with the following results. 1) Coffee consumption was significantly, inversely associated with weekly levels of estrone-3-glucuronide and human chorionic gonadotropin. 2) Weekly hours of nausea were significantly, directly associated with human chorionic gonadotropin and inversely with estrone-3-glucuronide and pregnanediol-3-glucuronide. 3) Weekly coffee consumption was significantly associated with vomiting but not with nausea or appetite loss. 4) Weekly levels of pregnanediol-3-glucuronide were 32.2% lower in subjects who drank at least 8 ounces of coffee/day at the last menstrual period, though above what was necessary to maintain those pregnancies. This study shows the significance of these important variables to be considered in future research.
A review of published and unpublished material was performed using medical databases, bibliographies and personal contact with peer experts to determine the best treatment of low-risk gestational ...trophoblastic neoplasia (GTN). Thirty-nine studies contained the minimum information required for inclusion in this study. Additional reports were retrieved but could not be disaggregated with sufficient accuracy to obtain valid comparative information. Four general regimen types were identified: methotrexate with/without folinic acid rescue, actinomycin, etoposide and 5-fluorouracil. The studies were compared based on effectiveness, cost and patient preference. Effectiveness and toxicity data were abstracted from the 39 studies. Intuitive assumptions about cost and preference were made to help differentiate the regimens. The following regimens were judged to be superior based on the data available: oral methotrexate, 100 mg/m2; infusional methotrexate; and pulse actinomycin. The small sample size of these 3 regimens limited the generalizability of the conclusions, but pulse actinomycin appeared to be the best choice given the data available. There is a paucity of level 1 and 2 evidence on the best chemotherapeutic management of low-risk GTN. A biochemical or consensus-based clinical definition of persistent disease and a standardized scoring system should be developed and used by future authors. The dearth of prospective, randomized information on this disease makes determination of the best practice and the choice of a best regimen problematic.
To evaluate whether chest computed tomography (CT) findings in patients with persistent gestational trophoblastic neoplasia (GTN) and a negative chest roentgenogram (CXR) significantly influence ...clinical outcome and to determine potential clinical predictors of pulmonary micrometastasis
The charts of 201 patients with nonmetastatic GTN (International Federation of Gynecology and Obstetrics FIGO stage I) receiving primary treatment with methotrexate (MTX) infusion between December 1985 and December 2000 were reviewed, and data were collected on age, gravidity and parity, FIGO stage, histologic diagnosis, metastatic disease, radiologic findings, surgery, presenting human chorionic gonadotropin (hCG) level, total number of chemotherapy courses and chemotherapeutic agents required to reach remission, and time to remission. The chi2, regression, Kaplan-Meier and log-rank tests were utilized to evaluate the correlation of chest CT with CXR findings, histology of antecedent pregnancy, presenting hCG level, chemotherapeutic requirements and time to remission.
Of 30 patients with a negative CXR, 13 (43.3%) had chest CT positive for micrometastasis. Histology of the antecedent pregnancy and mean presenting hCG did not correlate with the chest CT result. There was no significant difference between patients with positive or negative chest CT results in the requirement for > 1 dose of MTX or for additional chemotherapeutic agents. There also was no significant difference in time to remission by chest CT status. Regression analysis using histologic diagnosis, presenting hCG level, age, gravidity and parity as covariates did not reveal any clear risk factors for pulmonary micrometastasis.
It has been suggested that GTN patients with micrometastases identified on chest CT only are at increased risk of requiring > 1 dose of MTX or of requiring additional chemotherapeutic agents. Our data suggest that chest CT alone is not predictive of clinical outcome. Furthermore, the presence of micrometastases does not correlate with hCG level or histologic diagnosis, and there are no clear risk factors for pulmonary micrometastases.
To assess whether a complete hydatidiform mole (CHM) carries an increased risk of later requiring chemotherapy in pregnancies continued to term.
The Charing Cross gestational trophoblastic neoplasia ...(GTN) database was screened between 1973 and 2002 to identify registered singleton CHMs with a known gestational age at the time of evacuation. Of the 8,313 cases 2,800 were centrally histopathologically reviewed by us and confirmed as CHM. The proportion of patients requiring chemotherapyfor both total registered and centrally reviewed patients was analyzed by trimester of evacuation (< 13, 13-24, > 24 weeks). Statistical significance was assessed by the chi2 test.
For the total population, including non-centrally reviewed patients, evacuation occurring in the first, second or third trimester was associated with a treatment rate of 13.9% (601 of 4,333), 10.8% (412 of 3,803) and 5.1% (9 of 177), respectively. In patientsfor whom a central pathologic review had been performed to confirm the diagnosis, the treatment rates were 27.7% (525 of 1,897), 27% (241 of 893) and 20% (2 of 10). The higher apparent treatment rates reflect an error in the denominator as we do not review all nontreated cases. In the total population, evacuation in the third trimester correlated with a reduction in risk of subsequent treatment (P<.001). Most of these late deliveries were induced (before adequate ultrasound), whereas the earlier pregnancies were mostly terminated via suction dilatation and curettage.
There is no evidence that delayed evacuation/delivery of singleton CHM increases the risk of subsequently requiring chemotherapy.
To describe one institution's results with a novel 3-drug doublet, consisting of paclitaxel, etoposide and cisplatin, for salvage of relapsed high-risk gestational trophoblastic neoplasia (GTN) ...patients.
Analysis of treatment results with the doublet regimen in two patients with recurrent/persistent high-risk choriocarcinoma in the Division of Gynecologic Oncology, Toronto-Sunnybrook Regional Cancer Centre, University of Toronto. Both patients had been treated previously with one or more of the doublet drugs.
Both patients experienced complete responses, patient 1 for 13 months and patient 2 for 9. Patient 1 required surgical resection of a single focus of recurrence and was again in complete remission 27 months after completing her last course of doublet chemotherapy. Patient 2 has not relapsed since completing the treatment.
The doublet regimen appears capable of producing a sustained response in patients with recurrent high-risk GTN who have previously undergone extensive chemotherapy. Further, the regimen seems to be reasonably well tolerated.
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