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Human Chorionic Gonadotropin Tumor Marker

Human chorionic gnadotropin (hCG) is useful in evaluating and monitoring trophoblastic disease. Choriocarcinoma occurs in 5 to 10% of women who have a pregnancy associated with a hydatidiform mole. hCG levels are monitored during follow-up after evacuation of hydatidiform mole. These tumors excrete large amounts of hCG (100,000 mIU/mL) and the hormone levels do not decrease as in normal pregnancy but exhibit irregular fluctuations. Because the half‑life of hCG is 24 hours, levels may remain detectable for days following surgical removal. HCG becomes nondetectable within 8 weeks in 40% of patients, between 9 and 22 weeks in 55% of patients and in >22 weeks in 5%. If hCG returns to normal at a later date, a two year follow-up is required to rule out choriocarcinoma. Rising hCG levels at any time indicate cancer. hCG is a very sensitive marker for early choriocarcinoma and can detect tumors weighing only 1 mg. Monitoring hCG levels after detection of a hydatidiform mole has drastically reduced the death rate from trophoblastic tumors.

Elevated hCG levels may also be seen with testicular tumors, multiple pregnancy, polyhydramnios, eclampsia, erythroblastosis fetalis and several iron‑trophoblastic tumors (i.e. breast, hepatic, renal, adrenal, bronchogenic, pancreatic and gastrointestinal carcinomas, and leukemia, lymphoma and myeloma).See Alpha Fetoprotein, Tumor Marker. Specimen requirement is one SST tube of blood.

Persistent Low Levels of hCG

Persistent low levels of 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:

Medical Condition

# Cases

False positive

71

Quiescent GTD

69

Pituitary hCG

17

Active malignancy

13

Total

170

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 (Gynecol Oncol. 2006 Aug;102(2):165-72).

  1. Determine if the hCG is biologically real. The following criteria are used to identify false positive results (J Reprod Med, 49: 423-432, 2004).
    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.
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