What we know about low-level hCG: definition, classification and management.
OBJECTIVE
To critically assess the literature on the syndrome of low-level "real" human chorionic gonadotropin (hCG), to add new cases from our practice, to enumerate the investigations that are essential in the management of these patients and to offer a working classificationfor use by physicians encountering the condition.


METHODS
We report our experience with 9 patients with low-level hCG treated at the Yale Trophoblast Center and discuss London and Sheffield patients as well as reports from the USA hCG Reference Service.


RESULTS
One of the 9 Yale patients had developed placental site trophoblastic tumor metastatic to the lung. Following resection and 18 months of observation, she then had a successful pregnancy, has remained without evidence of disease and has negative hCG. The other patients continue to be observed. The experience from England shows that 2 of 14 patients with detectable hCG in urine and serum developed overt trophoblastic neoplasia and were treated successfully. The others are being followed. None have developed gestational trophoblastic neoplasia, 3 have regular menstrual periods, and 1 has had 2 pregnancies. The USA hCG Reference Laboratory has had 114 consultations. Sixty-three patients had real hCG and were followed for 6 months to 6 years. Forty of the 63 (63%) received single agent or combination chemotherapy, and 10 underwent hysterectomy, also. hCG persisted in spite of therapy. Four of the 63 (6%) eventually developed overt trophoblastic neoplasia and were then treated effectively; their hCG became negative. In these 4 patients whose hCG rose significantly and who did require therapy, the proportion of hyperglycosylated hCG became > or =80% of total hCG. In contrast, the proportion of hyperglycosylated hCG was always very low in the 63 quiescent cases.


CONCLUSIONS
Active therapy with chemotherapy or surgery for persistent, elevated, low-level, real hCG is counterproductive. Therapy should be initiated only if overt trophoblastic neoplasia appears. All patients with low-level, real hCG require sophisticated imaging to exclude the presence of extrauterine sites of trophoblast, such as trophoblastic metastases or pituitary adenoma. They require long-term follow-up with periodic clinical examination, imaging and frequent hCG testing with an assay that measures all aspects of the hCG molecule.
Yale Trophoblast Center, Department of Gynecology and Obstetrics, Yale University School of Medicine, New Haven, Connecticut 06510, USA. ernest.kohorn@yale.edu
Ernest I
EI
Kohorn
D000328:Adult; D006063:Chorionic Gonadotropin / Q000097:blood* / Q000652:urine*; D003951:Diagnostic Errors; D005189:False Positive Reactions; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D006828:Hydatidiform Mole / Q000175:diagnosis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011247:Pregnancy; D012016:Reference Values; D013577:Syndrome
D006063:Chorionic Gonadotropin