Thyroid function in trophoblastic disease

Summary. Human chorionic gonadotrophin (hCG) levels and thyroid function were monitored in 44 patients receiving chemotherapy for treatment of trophoblastic disease. We observed a strong correlation between hCG and thyroid stimulating hormone (TSH) concentrations measured by radioimmunoassay, and this appears to be due to cross-reactivity between hCG and the anti-TSH antibody used. The concentration of thyroid hormones was little affected by the raised levels of TSH or hCG, except when the concentration of the latter rose to high levels, usually above 100 000 i.u./l. The possible mechanisms of thyroid homeostasis in trophoblastic disease are considered.     

The use of plasmapheresis for rapid hormonal control in severe hyperthyroidism caused by a partial molar pregnancy

Introduction  The hormone human chorionic gonadotropin (hCG), secreted by molar tissue, is structurally similar to thyroid-stimulating hormone (TSH). Hyperthyroidism in trophoblastic disease is thought to be the result of TSH receptor activation by extremely elevated levels of hCG. Significant elevations in hCG levels are less common in cases of partial moles. Materials and methods   We describe a patient with partial molar pregnancy in which the levels of hCG and thyroid hormones were significantly high. It was not possible to decrease the elevated thyroid hormone concentrations to safer levels using medical treatment strategies only. Since the patient’s vaginal bleeding increased gradually, plasmapheresis was used to rapidly control the thyroid hormones during the preoperative preparation of the patient for anesthesia and surgery. After the evacuation of the molar tissue, the levels of the thyroid hormones detected after the plasmapheresis started to decrease even further. Conclusion  Plasmapheresis may be used as an alternative to antithyroid medication for the rapid control of thyroid hormones in cases of severe hyperthyroidism caused by molar pregnancy.     

The human chorionic gonadotropin molecule from patients with trophoblastic diseases has a high thyrotropic activity but is less active in the ovary

To examine the pathogenesis of hyperthyroidism in women with trophoblastic diseases, the biological activity of human chorionic gonadotropin (hCG) molecules in women with normal pregnancy (n?=?85) and in women with trophoblastic diseases (vesicular mole, n?=?30; and choriocarcinoma, n?=?12) was compared. Hyperthyroidism (thyroid stimulating hormone (TSH) <?0.3 mIU/l) was observed more frequently in women with trophoblastic diseases. All the sera were then subjected to Chinese hamster ovary cells transfected with the human TSH receptor (CHO-hTSHr cells) and cAMP production was compared. Sera from the women with choriocarcinoma showed the highest cAMP production. Interestingly, significant correlation between serum hCG level and cAMP production in CHO-hTSHr cells was observed only in women with trophoblastic disease. All the sera were then applied to CHO cells transfected with hCG/luteinizing hormone (LH) receptor (CHO-hCG/LHr cells). In contrast to the findings with the TSH receptor, sera from the women with normal pregnancy showed the highest cAMP production in these cells. Correlation between serum hCG level and cAMP production in CHO-hCG/LHr cells was significant only in normal pregnancy. These results indicate that the hCG molecule from women with trophoblastic diseases displays enhanced thyrotropic activity.     

Biochemical study on the thyrotropic activity in urinary immunoreactive-human chorionic gonadotropin of patients with trophoblastic disease

We have studied the biochemical properties of urinary immunoreactive-human Chorionic Gonadotropin (IR-hCG) using the human thyroid gland in vitro slice method to investigate the thyrotropic activity in purified IR-hCG of patients with thyroid hyperfunction associated with trophoblastic disease. IR-hCG was extracted using a kaolin-acetone-alcohol concentration and purified by DEAE Cellulose, Sephadex G-100 and DEAE Sephacel column chromatographies according to Nishimura et al. with slight modifications. The substance with thyrotropic activity (hCT) was found in 3 cases of trophoblastic disease with hyperthyroidism among the 14 cases investigated. HCT consists of two dissimilar subunits, namely, hCT alpha-subunit and hCT beta-subunit like hCG, whose molecular weights are estimated at about 15,000 and 20,000 respectively and have carbohydrate moiety bound to concanavalin A. The thyrotropic activity was shown by the recombinant hybrid molecules, hCT beta-subunit and hCG alpha-subunit, whereas no potency was found in hCT beta-subunit only. The carboxyterminal residues of hCT (Ile-Leu-Pro-Glu) were not digested by carboxypeptidases Band Y. These results suggest that hCT is an intrinsic activity of hCG and cross-reacts immunologically, while the amino acid residues of the carboxyterminus of the hCT beta-subunit are different from those of the hCG beta-subunit.     

Persistent low levels of human chorionic gonadotropin: A premalignant gestational trophoblastic disease

OBJECTIVE: This study was undertaken to evaluate the significance of persistent low-level human chorionic gonadotropin (hCG) titers (usually <50 IU/L) in the absence of clinical evidence of pregnancy or gestational trophoblastic disease. STUDY DESIGN: The USA hCG Reference Service consulted on 114 cases with persistent low levels of hCG; 51 had false-positive hCG results. The remaining 63 cases had real hCG results and are presented here. RESULTS: Antecedent gestational events included hydatidiform mole (27), pregnancy (35), and gestational trophoblastic neoplasm (1). Forty of the 63 (64%) cases received therapy, including chemotherapy (38), hysterectomy (2), or both (10). Despite treatment, in all cases, low hCG titers persisted. After 1 to 4.5 years of low titers, four women had a sudden rapid increase in hCG levels, and malignant disease was confirmed or clearly suggested (gestational trophoblastic neoplasm [3] and placental site trophoblastic tumor [1]). Invasive trophoblast antigen (ITA) is a marker of invasive cytotrophoblast cells. ITA was measured in 38 of the cases with persistent low hCG, in all cases ITA accounted for less than 25% of the hCG concentration. It was also determined in the 4 cases indicated with malignant disease, accounting for more than 80% of the hCG. CONCLUSION: The presence of persistent low-level hCG titers defines a subset of women with preinvasive or quiescent gestational trophoblastic disease. ITA effectively detected the presence or absence of invasive cells in these cases. The recommended management of the quiescent disease is close surveillance without therapy until malignant disease detected.     

The role of hCG in regulation of the thyroid gland in normal and abnormal pregnancy.

There is strong evidence that at least some forms of hCG can interact with and stimulate the thyroid both in vitro and in vivo. Changes in thyroid tests are sufficiently common in normal pregnancy for us to regard them as physiologic. The evidence that hCG is the agent responsible for these changes remains largely circumstantial but is now supported by an increasing body of evidence from laboratory studies. Trophoblastic tumors secrete variant forms of hCG that can stimulate the thyroid, but we do not know if they have any role in the extreme examples of thyroid stimulation encountered in normal pregnancy. Preparations of hCG from pregnancy urine bind to thyroid membranes from a wide variety of species, but they do not activate adenylate cyclase in all assay systems. The enzyme in human thyroid cells or membranes is, at best, only weakly stimulated by hCG. There are ample in vitro data that hCG can stimulate the thyroid, but studies using human thyroid cells have yielded conflicting results. The most direct evidence comes from the study of thyroid tests in normal pregnancy. In early pregnancy, when hCG concentrations are highest, free thyroid hormones are increased and serum TSH concentration is decreased. An inverse correlation exists between serum hCG and TSH concentrations, but hCG generally correlates poorly with individual thyroid tests. An activity in pregnancy serum related to hCG is able to stimulate FRTL-5 cells and may account for the changes in thyroid function observed in pregnancy. Structural considerations, along with data from biologic assays and sensitive thyroid function tests, suggest that hCG has significant thyroid-stimulating activity. This information suggests that the thyroid may be under dual control from both hCG and TSH in early pregnancy.     

Serum levels of macrophage colony-stimulating factor in trophoblastic disease

OBJECTIVES: The aims of this study were to measure levels of colony stimulating factor (CSF-1) in patients with trophoblastic disease, to determine whether such measurement may be useful to supplement measurement of the prognostically reliable human chorionic gonadotrophin (hCG), and to assess whether measurement of CSF-1 may be helpful in predicting requirement for chemotherapy in patients with hydatidiform mole. METHODS: Serial weekly serum samples were selected for CSF-1 assay from representative diagnostic groups of patients with trophoblastic disease: hydatidiform-mole with spontaneous resolution, low-risk post-hydatidiform-mole trophoblastic tumor, partial hydatidiform mole, high-risk metastatic gestational trophoblastic tumor, primary ovarian choriocarcinoma, and placental site trophoblastic tumor. hCG was measured by an in-house radioimmunoassay that measures all parts of the hCG molecule. CSF-1 was measured by radioimmunoassay with (125)I-labeled recombinant CSF-1. The upper level of normal CSF-1 was taken as 8 ng/ml. RESULTS: In this study of 45 patients with trophoblastic disease, some very high levels of CSF-1 were encountered. In a few patients there was dramatic correlation with hCG. Generally, however, CSF-1 and hCG did not correlate. CSF-1 was frequently not elevated when hCG was still significantly elevated and conversely CSF-1 was elevated when hCG was negative. CONCLUSION: The measurement of CSF-1 does not appear to be useful in managing trophoblastic disease as it does not correlate with the level of hCG. Occasionally, high levels of CSF-1 were found in patients with trophoblastic disease.     

The hCG assay in the treatment of trophoblastic disease

The most important criterion in monitoring the treatment of patients with trophoblastic disease is the quantitative measurement of hCG levels. It is particularly important to have a sensitive hCG-detection procedure that reliably distinguishes low positive hCG levels from negative ones. Reliable monitoring of serum hCG levels minimizes unnecessary chemotherapy in patients entering remission and provides an early indication for additional chemotherapy if and when the hCG levels again become detectable. We evaluated a two-site monoclonal-antibody immunoradiometric assay (IRMA) for its reliability in the management of trophoblastic disease. The assay utilizes a solid-phase, monoclonal antibody that recognizes the alpha subunit of complete hCG and a 125I monoclonal antibody that recognizes the beta subunit. The minimal effective concentration of hCG detectable with the IRMA is 3-4 mIU/ml. The study population consisted of 6 choriocarcinoma patients, 49 hydatidiform mole patients, 37 patients being monitored after spontaneous abortion or blighted ovum and 80 patients in whom the possibility of trophoblastic disease was being ruled out. Each serum specimen was analyzed with the IRMA and in one or more of a number of different radioimmunoassays. The results were correlated with the patient's clinical course. Of the procedures evaluated, the IRMA was the most reliable in identifying trophoblastic-disease patients who required additional chemotherapy. Furthermore, the IRMA yielded no persistent low positive hCG values in patients without clinical evidence of trophoblastic disease. Therefore, the two-site IRMA is recommended for accurately distinguishing a clinically relevant low positive hCG level from an undetectable one.     

Physiologic thyroid activation in normal early pregnancy is induced by circulating hCG

In normal early pregnancy, serum free thyroxine (T4) increases and serum TSH decreases, indicating that the thyroid gland is activated physiologically. To identify the factor responsible for this thyroid activation, we measured the serum thyroid-stimulating activity in comparison with the serum level of hCG in 39 normal women in early pregnancy. Serum thyroid-stimulating activity was measured by a sensitive cyclic adenosine 3',5'-monophosphate (cAMP) accumulation assay using a rat thyroid cell line (FRTL-5). Thyroid-stimulating activity was detected in 37 women (95%), and the activities of individuals correlated positively with their serum free T4 levels (r = 0.474; P less than .01) and negatively with their serum TSH levels (r = -0.376; P less than .02). Moreover, serum thyroid-stimulating activity correlated closely with the serum hCG level (r = 0.741; P less than .001), but was completely abolished by pre-treatment of the sera with hCG antibodies. These data indicate that in normal early pregnancy, the thyroid gland is physiologically activated by serum hCG, which has intrinsic thyroid-stimulating activity.     

Nicked human chorionic gonadotropin in trophoblastic disease

Abstract. Kohorn EI, Cole L. Nicked human chorionic gonadotropin in trophoblastic disease.
The objectives of this study were to determine: 1) whether high proportions of nicked human chorionic gonadotropin (hCG) in serum at the time of mole evacuation and during postmolar surveillance is indicative of trophoblastic malignancy and 2) to investigate whether measurement of nicked hCG provides clinically more useful information in the management of patients with trophoblastic disease than does measurement of total hCG alone.
"Tumor marker" total hCG, intact hCG, and nicked hCG were measured in serial samples of serum from our serum bank of patients with representative types of trophoblastic disease. "Tumor marker" hCG has been shown to measure all aspects of the hCG molecule. At the time of presentation of all 45 patients, 83.5% of hCG was intact and 16.5% was nicked. These proportions became reversed as hCG declined either spontaneously after hydatidiform mole evacuation or with chemotherapy in patients with postmolar trophoblastic tumor or with metastatic trophoblastic disease.
We conclude that the proportion of nicked hCG compared to intact hCG increases with trophoblastic disease resolution. Measurement of nicked hCG adds no useful clinical information to that provided by reliable measurement of total hCG.     

Blood test for placental site trophoblastic tumor and nontrophoblastic malignancy for evaluating patients with low positive human chorionic gonadotropin results

OBJECTIVE: To examine utility of measurement of proportions of free beta-subunit of human chorionic gonadotropin (hCG) in diagnosis of placental site trophoblastic tumor (PSTT) and nontrophoblastic neoplasm in patients with persistent low hCG levels and patients with history of gestational trophoblastic diseases. STUDY DESIGN: The USA hCG Reference Service measured proportions of free beta-subunit in 128 cases, 45 with active invasive trophoblastic disease and 83 questionable cases with persistent low hCG levels, with or without history of gestational trophoblastic disease (GTD). RESULTS: High proportions of free beta-subunit (> 30% of total hCG) were identified in 18 of 128 cases, all suspected of having PSTT or nontrophoblastic neoplasm, which was reported to referring physicians. Within 2 months of testing, hysterectomy or tumor biopsy led to histologic proof of PSTT in 13 of the 18 cases and biopsy led to proof of nontrophoblastic neoplasm in 5 of the 18 cases. CONCLUSION: We confirm use of proportion of free beta-subunit (> 30%) as a seemingly absolute test for identifying PSTT and nontrophoblastic neoplasms. It should be used to identify and diagnose these malignancies in women presenting with persistent low hCG levels outside of pregnancy and in secondary evaluation of patients with a history of GTDs.     

An unusual cause of cardiothyreosis

Severe hyperthyroidism can cause cardiac complications, such as severe rhythm disturbances, heart failure and angina. Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from benign hydatidiform mole to malignant form. Clinical hyperthyroidism may occur in GTD, as human chorionic gonadotropin (hCG) secreted by molar tissue is structurally similar to thyroid-stimulating hormone. Cardiothyreosis in this context is exceptional. We report the case of a nulligravida 42-year-old woman without thyroid or cardiac history who presented to the emergency department for dyspnoea. Examinations revealed an acute pulmonary oedema and sinus tachycardia. Serum hCG concentration was abnormally high (762?878?UI/l, N?相似文献   

Gestational trophoblastic disease: is intensive follow up essential in all women?

OBJECTIVE: To determine the timescale of the registration process for gestational trophoblastic disease and its impact on hCG level at registration and subsequent need for chemotherapy. DESIGN: A prospective observational study using a standardised protocol for registration, assessment and treatment for molar pregnancy. SETTING: A supra-regional tertiary referral centre for gestational trophoblastic disease. PARTICIPANTS: A total of 2046 consecutive women registered between January 1994 and December 1998 with a diagnosis of molar pregnancy. METHODS: Data at and after registration, collected prospectively on a computerised database, were statistically analysed (by multiple logistic regression and ANOVA). MAIN OUTCOME MEASURES: Relationship between length of time to and hCG value at registration; also the subsequent need for chemotherapy. RESULTS: A total of 2046 women with a diagnosis of molar pregnancy were registered in the study period. The mean time interval between first evacuation and registration at the referral centre was 47 days (median 37, range 0-594). One hundred and five out of 2046 (5.1%) women needed chemotherapy. Sixty-three precent of the women (1296 out of 2046) had a normal level of urinary hCG (less than 40 IU/24 hours) at the time of registration and only one (0.08%) needed chemotherapy. Binary logistic regression analysis showed a statistically significant relationship between time to registration, hCG value, histology, pretreatment risk score and decision to administer chemotherapy. CONCLUSION: Women with gestational trophoblastic disease who were registered late were significantly more likely to have normal levels of hCG and were less likely to need chemotherapy. A less intensive follow up may be justified in women with gestational trophoblastic disease who are registered with a normal hCG level.     

Trophoblastic disease monitoring: Evaluation of pregnancy-specific beta 1-glycoprotein

Pregnancy-specific beta 1-glycoprotein (SP1) was evaluated as a potential marker protein for monitoring trophoblastic disease. Four patients with post-molar pregnancy accompanied by spontaneous titer remission and three patients with nonmetastatic trophoblastic disease were found to have regression curves for both human chorionic gonadotropin (hCG) and SP, which closely followed each other. Of three patients with metastatic choriocarcinoma, two were shown to have discordant hCG and SP1 patterns, SP1 in both cases was plateauing or rising while hCG continued to fall. Two other patients are described, one with a spontaneous remission, and one who previously had had choriocarcinoma and was found to have low levels of hCG with higher levels of SP1.     

Thyroid function in gestational trophoblastic neoplasia: evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma

An investigation was made of thyroid function in 20 patients with gestational trophoblastic neoplasia. Two patients were judged to be overtly thyrotoxic on the basis of the symptoms and physical findings; both patients had widely metastatic choriocarcinoma, markedly increased serum T4 levels (21.4 and 27.7 micrograms/100 ml), and extremely high levels of serum human chorionic gonadotropin (hCG) (3,220 and 6,720 IU/ml) relative to those of normal gestation(< 100 IU/ml). Three other patients had moderately increased serum T4 levels (13 to 17.1 micrograms/100 ml), moderately increased serum hCG levels (110 to 310 IU/ml), and findings on clinical examination which suggested euthyroidism. Using the mouse thyroid bioassay, we found that the biologic characteristics of the thyroid-stimulating factor were those of purified hCG, and that the levels of thyroid-stimulating activity in both serum and urine correlated closely with the levels of hCG. These results provide evidence that the thyroid-stimulating activity intrinsic to the hCG molecule plays the central pathophysiologic role in choriocarcinoma-associated thyrotoxicosis.     

正常孕妇垂体-甲状腺轴功能变化的研究

目的了解正常孕妇妊娠各期及产后垂体-甲状腺轴功能的变化;探讨妊娠期人绒毛膜促性腺激素(hCG)对垂体-甲状腺轴的调节作用.方法采用放射免疫法,测定正常孕妇妊娠早、中、晚期及产后甲状腺功能参数[血清总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)、血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)]、hCG及甲状腺结合球蛋白(TBG)的水平.结果(1)血清TT3、TT4水平在妊娠各期均较产后显著升高,其中TT4在妊娠早期最高为(170.00±40.28)nmol/L,TT3在妊娠中期最高为(2.64±0.53)mmol/L.(2)血清FT3水平在妊娠早期[(4.37±0.78)pmol/L]和中期[(4.75±0.90)pmol/L]显著升高,晚期[(3.94±0.75)pmol/L]下降,产后最低(2.96±0.84)pmol/L];血清FT4妊娠早期最高[(14.07±1.44)pmol/L],中期[(12.86±0.84)pmol/L]和晚期(11.29±1.00)pmol/L]逐渐下降,产后[(10.45±1.45)pmol/L]最低.(3)血清TSH水平在妊娠早期最低为(0.88±0.83)mU/L,妊娠中期[(1.86±1.04)mU/L]和晚期[(1.48±0.90)mU/L]上升,产后(2.82±1.42)mU/L]达最高峰.(4)血清hCG水平在妊娠早期最高为(309.05±320.02)μg/L,中期(69.11±19.18)μg/L]和晚期[(86.25±44.60)μg/L]下降,产后[(29.95±20.91)μg/L]最低.(5)hCG与TSH呈负相关,而与FT4、TT4呈正相关.结论(1)hCG可能在整个妊娠期及产后一定时间内,对垂体-甲状腺轴功能有一定的调节作用.(2)产后部分孕妇处于一过性甲状腺功能低减状态.     

Hipertiroidismo como manifestación de la enfermedad trofoblástica gestacional: a propósito de un caso

Gestational trophoblastic disease (GTD) is a group of tumours caused by the hyperproliferation of trophoblast cells and is noted for its overproduction of hCG. Among its manifestations, there may be hyperthyroidism, due to the stimulating activity of hCG on TSH receptors. In most cases it is only a biochemical hyperthyroidism, with its presentation as symptomatic hyperthyroidism being much less frequent. We report the case of a patient with GTD, who at diagnosis presented with symptomatic hyperthyroidism. Treatment included surgical evacuation of the hydatidiform mole, as well as a beta-blocker and antithyroid drug treatment to relieve the symptoms.     

Racial comparisons of thyroid function and autoimmunity during pregnancy and the postpartum period

OBJECTIVE: To evaluate thyroid function and the prevalence of thyroid peroxidase (TPO) antibody and autoimmunity in African-American and white women during pregnancy and the postpartum period. METHODS: Five hundred eighty-nine women were evaluated prospectively. Serum thyroid-stimulating hormone (TSH), free thyroxine (T4), and TPO, Ro, and La antibodies were obtained during pregnancy, at delivery, and postpartum. Levels of hCG were determined during pregnancy. Urinary iodine levels were evaluated in the third trimester in another group of women. All TPO antibody-positive patients were to be followed up at 3 and 6 months postpartum. RESULTS: African-American women had lower TSH values than white women at all times. Thyroid-stimulating hormone increased, and free T4 decreased from the first to third trimester of pregnancy for both groups. African Americans had higher hCG levels than whites in the first trimester but not in the third trimester. There was no difference in urine iodine excretion between African-American and white women. Finally, there was no difference in TPO antibody seropositivity between African-American and white women. Overall, 5 patients (0.8%) were diagnosed with subclinical hypothyroidism during pregnancy. CONCLUSION: Fluctuations in TSH and free T4 during pregnancy parallel reported obstetric values. African Americans demonstrated consistently lower TSH levels than whites. These differences were unexplained by racial differences in either TPO antibody seropositivity, iodine status, or chorionic gonadotropin levels.     

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was -0.21 which was statistically significant (p=0.02, 95% confidence interval -0.38 to -0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester.     

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.