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Clinical Significance

Pregnancy

HCG is an important hormone in pregnancy, and its clinical utility is primarily centered around its detection in early pregnancy, along with serial measurement during pregnancy and pregnancy-related complications.

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Levels of hCG can vary widely between women with normal pregnancies. Typically, serum and urine concentrations of hCG rise exponentially in the first trimester of pregnancy, doubling about every 24 hours during the first 8 weeks. The peak is usually around 10 weeks of gestation and then levels decrease until about the 16th week of gestation where they remain fairly constant until term.[3]

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Patients who have hCG levels that plateau prior to 8 weeks or that fail to double commonly have a nonviable pregnancy, whether intra-uterine or extra-uterine. Extra-uterine (ectopic) pregnancies usually have a rate-of-rise that is low without the typical doubling. However, given the large range of normal hCG levels and inconsistent rates-of-rise of this hormone, checking serum levels is typically paired with ultrasound evaluation to improve sensitivity and specificity.[20]

Return of hCG to zero following delivery or termination of pregnancy ranges from 7 to 60 days.[21] Trending the fall of hCG levels can be important in termination of molar pregnancies and also following the termination of normal or ectopic pregnancies to be assured that the therapy has been successful.

It notable that there are many different combinations of antibodies used in commercial assays. This results in heterogeneous results with as much as a 50-fold difference in immunoassay results.[3] This is clinically relevant, particularly when comparing results from different laboratories in different facilities/hospitals when examining low values following pregnancy termination or trophoblastic disease.

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Gestational Trophoblastic Disease

Detection of hCG is also useful in the evaluation of trophoblastic disease, including complete and partial hydatidiform mole, postmolar tumor, gestational choriocarcinoma, testicular choriocarcinoma, and placental site trophoblastic disease. All of these entities produce hCG, varying levels of which are reported on commercial assays. A total hCG level of greater than 100,000 mIU/mL in early pregnancy, for example, is highly suggestive of a complete hydatidiform mole,[22] although many normal pregnancies may reach this level at their peak around weeks 8 to 11 of gestation. Precise hCG measurements are important to assess the tumor mass, the successful treatment of malignancy, and to test for recurrence or persistence of disease.[6]

Non-Pregnant Patients

HCG in the serum increases with age in nonpregnant women. A cut off of 14 mIU/mL has been suggested for use in interpreting results in women over the age of 55. In all nonpregnant patients, testicular cancer, ovarian cancer, bladder cancer, or other malignancy should be evaluated as a source of persistently positive hCG testing.

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