Human chorionic gonadotropin, free beta-subunit

Human chorionic gonadotropin, free beta-subunit testing (free β-hCG; hCG, free beta-subunit) is incorporated into first- and second-trimester maternal screening to estimate risk for fetal chromosomal aneuploidy. Results are used to diagnose and monitor gestational trophoblastic disease and to assess response to treatment. As a tumor marker, free β-hCG supports evaluation and longitudinal follow-up of testicular germ cell tumors and assists in recognizing ectopic hCG production by nontrophoblastic malignancies.

Human chorionic gonadotropin (hCG) is a 37.5 kDa glycoprotein composed of a common alpha chain and a hormone-specific beta chain. The alpha subunit is shared with luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone, whereas the beta subunit confers biological specificity. During pregnancy, synthesis occurs predominantly in the syncytiotrophoblast, with low-level pituitary production also present; most circulating hCG undergoes hepatic metabolism, and approximately 20% is excreted in urine. In early gestation (about weeks 2–5), circulating free β-hCG rises rapidly and may be proportionally higher with multiple gestations, peaking near weeks 10–11 before declining thereafter. Measurement of the free beta subunit is part of first- and second-trimester aneuploidy screening algorithms: elevated first-trimester maternal serum concentrations are associated with trisomy 21 risk, whereas reduced concentrations may be observed with trisomy 18. Free β-hCG also aids in diagnosing and monitoring gestational trophoblastic disease (eg, hydatidiform mole, choriocarcinoma) and may be increased in testicular germ cell tumors and certain nontrophoblastic cancers that ectopically produce hCG; serial measurements are used to monitor therapeutic response.