Human Chorionic Gonadotropin Persistence

Persistent low levels of human chorionic gonadotropin (hCG) pose an infrequent but serious challenge to clinicians and laboratories. A recent publication indicates that a number of patients with low hCG levels and no evidence of pregnancy or imaging evidence of tumor have been subjected to unnecessary surgery and/or chemotherapy for misdiagnosed malignancy.  A set of guidelines has been recommended to properly manage patients with persistently low hCG levels.

Researchers at the USA hCG Reference Service recently published data on serum samples from 170 women with low levels of hCG persisting for three months or longer that were sent to the service for consultation. The hCG levels ranged from 6.1 – 900 mlU/ml with an average result of 102 ± 152 mlU/ml. Of the 170 patients in the study, 13 were found to have a malignancy and the remaining 157 patients had false positive hCG, quiescent gestational trophoblastic disease (GTD) or pituitary hCG:

One hundred and eight (69%) of the 157 patients without a malignancy underwent unnecessary  therapy including surgery and/or chemotherapy before consultation with the Reference Service. Forty-seven of the 71 patients with false positive hCG received chemotherapy and 9 underwent surgery. Forty-one of the 69 patients with a quiescent GTD received chemotherapy and 9 underwent hysterectomy. Two of the 17 patients with pituitary hCG received chemotherapy. hCG levels were unaffected by treatment in these patients.

Based on these findings, the USA hCG Reference Service proposed guidelines for managing patients with persistent low levels of hCG.

1. Determine if the hCG is biologically real. The following criteria are used to identify false positive results.
1. The finding of a >5-fold difference in serum hCG results or negative hCG results with an alternative laboratory serum hCG test (essential criterion).
2. The presence of hCG in serum and absence of detectable hCG or hCG-related molecule in a parallel urine sample (essential criterion).
3. The observation of false positive results in other tests for molecules not normally present in serum, such as urine ß-core fragment (confirmatory criterion).
4. The finding that a heterophilic antibody-blocking agent prevented or limited false detection (confirmatory criterion).
2. Send serum samples to a specialty laboratory.  If the measured hCG is real, the serum samples should be sent to a specialty laboratory to determine if active gestational trophoblastic neoplasm, placental site trophoblastic tumor or non-trophoblastic malignancy is present. 
3. Determine if the hCG is of pituitary origin.  If the patient is peri- or post-menopause, or has had an oophorectomy, then pituitary hCG is likely. In that case, the patient should take hormone replacement therapy or oral contraceptives. After 2-3 weeks, this should suppress hCG production if it is of pituitary origin.

References

Cole LA, et al, Gestational trophoblastic diseases: 4: Presentation with persistent low positive human chorionic gonadotropin test results, Gynecol Oncol, 2006;102(5):165-72.

Cole LA, Khanlian SA, Inappropriate management of women with persistent low hCG results, J Reprod Med, 2004;49(6):423-432.