Clinical Information

Human chorionic gonadotropin (hCG) is a glycoprotein hormone (molecular weight: MW approximately 36,000 Da) consisting of 2 noncovalently bound subunits. The alpha subunit (92-amino acids; "naked" protein MW 10,205 Da) is essentially identical to that of luteinizing hormone (LH), follicle-stimulating hormone, and thyrotropin (previously known as thyroid-stimulating hormone: TSH). The alpha subunit is essential for receptor transactivation. The different beta subunits of the above hormones are transcribed from separate genes, show less homology, and convey the receptor-specificity of the dimeric hormones. The chorionic gonadotropin, beta gene (coding for a 145-amino acid, "naked" protein MW 15,531 Da, glycosylated subunit MW approximately 22,500 Da) is highly homologous to the beta subunit of LH and acts through the same receptor. However, while LH is a classical tropic pituitary hormone, hCG does not usually circulate in significant concentrations. In pregnant primates (including humans) it is synthesized in the placenta and maintains the corpus luteum and, hence, progesterone production, during the first trimester. Thereafter, the placenta produces steroid hormones, diminishing the role of hCG. hCG concentrations fall, leveling off around week 20, significantly above prepregnancy levels. After delivery, miscarriage, or pregnancy termination, hCG falls with a half-life of 24 to 36 hours, until prepregnancy levels are reached.

Outside of pregnancy, hCG may be secreted by abnormal germ cell, placental, or embryonal tissues, in particular seminomatous and nonseminomatous testicular tumors; ovarian germ cell tumors; gestational trophoblastic disease (hydatidiform mole and choriocarcinoma); and benign or malignant nontesticular teratomas. Rarely, other tumors including hepatic, neuroendocrine, breast, ovarian, pancreatic, cervical, and gastric cancers may secrete hCG, usually in relatively modest quantities.

During pathological hCG production, the highly coordinated secretion of alpha and beta subunits of hCG may be disturbed. In addition to secreting intact hCG, tumors may produce disproportionate quantities of free alpha-subunits or, more commonly, free beta-subunits. Assays that detect both intact hCG and free beta-hCG, including this assay, tend to be more sensitive in detecting hCG-producing tumors.

With successful treatment of hCG-producing tumors, hCG levels should fall with a half-life of 24 to 36 hours, and eventually return to the reference range.