What we know about low-level hCG: definition, classification and management

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.

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.

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.

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.