What is HCG (Human Chorionic Gonadotropin)?

Human Chorionic Gonadotropin (hCG): Definition, Function, and Clinical Applications

Human chorionic gonadotropin (hCG) is a polypeptide hormone produced by trophoblastic cells during pregnancy that functions primarily to maintain the corpus luteum and support pregnancy development. 1, 2

Definition and Structure

• hCG is a complex glycoprotein composed of two highly glycosylated subunits (alpha and beta) 3
• The alpha subunit is identical to other pituitary gonadotropins (LH, FSH, TSH), while the beta subunit is unique to hCG and confers its specific biological activity 4, 3
• The beta subunit contains two sites of N-glycosylation and four sites of O-glycosylation 3, 5
• Laboratory terminology note: The "beta" modifier for hCG may no longer be used by some laboratories, so refer to local laboratory guidelines for specific terminology 1, 2

Production and Sources

• Primary production occurs in the placenta, specifically by:
  • Syncytiotrophoblast cells (producing regular hCG) 3, 5
  • Extravillous invasive cytotrophoblast cells (producing hyperglycosylated hCG) 3, 5
• Detectable in maternal blood as early as two days after implantation 3, 5
• Peaks at approximately 8-10 weeks of gestation 3, 5
• Rarely, elevated hCG may be unrelated to pregnancy, such as with pituitary dysfunction or neoplasia 1, 2

Biological Functions

Pregnancy-Related Functions

• Acts as a super LH agonist by binding to the LH/CG receptor 4
• Maintains corpus luteum function and stimulates progesterone production during early pregnancy 4, 3
• Promotes formation of the syncytiotrophoblast 3, 5
• Supports trophoblast invasion during implantation (particularly hyperglycosylated forms) 3, 6, 5
• Promotes angiogenesis in the uterine endothelium 3, 7
• Maintains myometrial quiescence 3, 7
• Supports local immune tolerance at the maternal-fetal interface 3, 7

Non-Pregnancy Functions

• In males, stimulates Leydig cells to produce androgens 4
• May stimulate testicular descent when no anatomical impediment exists 4
• Important note: hCG has NO KNOWN EFFECT on fat mobilization, appetite, sense of hunger, or body fat distribution 4

Clinical Applications

Pregnancy Detection and Monitoring

• Serum hCG >5 mIU/mL indicates pregnancy (with rare exceptions) 1
• Used for early pregnancy detection and confirmation 8, 6
• Helps monitor pregnancy progression and outcomes 8, 6
• Different glycoforms of hCG have different clinical significance:
  • Regular hCG: primary form throughout pregnancy 3, 5
  • Hyperglycosylated hCG: elevated in early first trimester, marker of trophoblast invasion 3, 5

Gestational Trophoblastic Disease (GTD)

• Essential in diagnosing and monitoring hydatidiform mole, invasive mole, and choriocarcinoma 1
• Persistent elevated hCG after evacuation of a molar pregnancy often indicates invasive mole 1
• Approximately 15-20% of complete moles and 1-5% of partial moles develop into post-molar GTN 1
• Monitoring involves measuring serum hCG at least once every 2 weeks until normalization 1

Other Clinical Applications

• Used in antenatal screening for chromosomal abnormalities 8, 5
• Helpful in diagnosing and managing testicular and other germ cell malignancies 8, 6
• Used to evaluate unexplained persistent low-level elevated hCG 1

Important Clinical Considerations

• For hemodynamically stable patients with no sonographic evidence of intrauterine or ectopic pregnancy, management decisions should generally not be made based on a single hCG level 2
• Different hCG assays may detect different forms of hCG with varying sensitivity 8
• In cases of unexplained persistent low-level hCG, consider:
  • False-positive results due to assay-interfering molecules 1
  • Pituitary hCG production (especially in perimenopausal/menopausal women) 1
  • Renal failure (affecting hCG clearance) 1
  • Familial elevated hCG syndrome (rare) 1
  • Gestational or non-gestational tumors producing hCG 1