Interpretation

Specimens are evaluated for potential heterophile antibody interference in the Roche Elecsys total beta-human chorionic gonadotropin (hCG) immunoassay. Evaluation consists of pretreatment with commercial heterophile antibody blocking tube reagents, serial dilution of the sample, and testing on an alternate platform (Beckman Coulter DxI). The presence of heterophile antibody interference in the Roche Elecsys assay is not suspected when the results from the pretreatment, serial dilution, and the alternative platform agree within 20% of the original result.

The presence of heterophile antibody interference in the Roche Elecsys assay is suspected when 1 or more of the following are observed: a significant decrease in hCG (>20%) upon treatment of the sample with heterophile antibody blocking reagents, lack of linearity upon serial dilutions, or a significant difference in hCG concentration on the alternate platform. When a heterophile antibody interference affecting the Roche Elecsys assay is suspected, the hCG results from this assay are considered false-positive results and should not be used in clinical management.

Heterophile reagent blocking tubes (HBT-Scantibodies) contain a unique blocking reagent composed of specific binders, which inactivate heterophilic antibodies. Once the specific binders have bound to the heterophilic antibodies, the antibodies are no longer able to cause immunoassay interference. Blocking agents do not inhibit all heterophilic antibodies completely and cannot be used to rule out the presence of heterophile antibody interference.

For patients with apparent serum hCG concentrations greater than 15 to 20 IU/L, hCG should also be detectable in urine if it is truly elevated. Failure to detect urinary hCG in such patients can support the suspicion of a false-positive serum hCG test.

After delivery, miscarriage, or pregnancy termination, hCG levels fall with a half-life of 24 to 36 hours, until prepregnancy levels are reached. An absent or significantly slower decline is seen in patients with retained products of conception.

Gestational trophoblastic disease (GTD) is associated with very considerable elevations of hCG, usually above 2 multiples of the median for gestational age persisting, or even rising beyond, the first trimester.

Serum hCG levels are elevated in approximately 40% to 50% of patients with nonseminomatous testicular cancer and 20% to 40% of patients with seminoma. Markedly elevated levels of hCG (>5000 IU/L) are uncommon in patients with pure seminoma and indicate the presence of a mixed testicular cancer.

Ovarian germ cell tumors (approximately 10% of ovarian tumors) display elevated hCG levels in 20% to 50% of cases.

Teratomas in children may overproduce hCG, even when benign, resulting in precocious pseudopuberty. Levels may be elevated to similar levels as seen in testicular cancer.

Among nonreproductive tumors, hepatobiliary tumors (hepatoblastomas, hepatocellular carcinomas, and cholangiocarcinomas) and neuroendocrine tumors (eg, islet cell tumors and carcinoids) are those most frequently associated with hCG production.

Many hCG-producing tumors also produce other embryonic proteins/antigens, in particular alpha fetoprotein (AFP). Therefore, AFP should also be measured in the diagnostic workup of such neoplasms.

Complete therapeutic response in hCG-secreting tumors is characterized by a decline in hCG levels with an apparent half-life of 24 to 36 hours and eventual return to concentrations within the reference range. GTD and some tumors may produce hyperglycosylated hCG with a longer half-life, but an apparent half-life of greater than 3 days suggests the presence of residual hCG-producing tumor tissue.

A rise in hCG levels above the reference range in patients with hCG-producing tumors that had previously been treated successfully suggests possible local or distant metastatic recurrence.