hCG Testing - hCG

Diagnosis

Indications for Testing

• Rule out pregnancy and evaluate for gestational trophoblastic disease

Laboratory Testing

• Serum
  • Quantitative
    • hCG variant detection (different assays do not all detect the same hCG variants)
      • Important to use same assay for serial tests
      • In a viable pregnancy, hCG will usually double over 48 hours
  • Qualitative
    • Rapid but not as sensitive as quantitative
    • Should use quantitative if detection of pregnancy is critical
• Urine
  • Qualitative only
    • hCG is highest in first morning urine specimen
    • False negatives may occur due to high concentrations of hCGβcf (core fragment)
• Positive/elevated hCG
  • Positive results should be consistent with clinical picture
    • Consider age, symptoms, etc
      • Goal is to avoid delays in needed treatment and to identify true false positives needing no treatment
    • If inconsistent, then rule out
      • False-positive hCG (interfering antibody)
        • Urine hCG
        • Serial dilution
        • Blocking agents
      • Pituitary hCG
        • Serum FSH
          • FSH >45 essentially rules out pregnancy
          • Estrogen replacement for ~2 weeks with repeat testing; if source is pituitary, hCG will be suppressed to ≤2 IU/mL
          • Pituitary hCG should be considered to avoid unnecessary chemotherapy for choriocarcinoma when no true trophoblastic disease is present

Imaging Studies

• Pelvic ultrasound to rule out viable pregnancy or possible ectopic pregnancy

Differential Diagnosis   

• Pregnancy       
• Gestational trophoblastic disease
• Menopause
• Germ cell tumor (testicular, ovarian)

Clinical Background

Human chorionic gonadotropin (hCG) is produced in elevated levels during pregnancy as well as with gestational trophoblastic disease and some germ cell tumors. Additionally, hCG concentrations of a pituitary origin are sometimes detected in peri- and post-menopausal women and are not always indicative of pregnancy.

hCG tests are performed on many female patients before performing medical procedures or administering medication that may harm a fetus. The interpretation of low-level hCG elevation in these females is problematic because these elevations might represent gestational trophoblastic disease or other malignancies, or they might be benign.

Pathophysiology

• hCG biochemistry (basic)
  • Sources of hCG
    • Pregnancy
    • Malignancy (gestational trophoblastic neoplasm, testicular cancer)
    • Pituitary
  • hCG variants in serum and urine
    • Intact hCG
    • Nicked hCG (hCGn)
    • Free β subunit (hCGβ)
    • Nicked free β subunit (hCGβb)
    • β core fragment (hCGβcf) – urine only
  • Serum and urine levels are parallel during pregnancy
• Synthesis and function in pregnancy
  • Produced by syncytiotrophoblast cells of the developing placenta
  • Functions to stimulate the corpus luteum in the ovary to synthesize progesterone during the first weeks of pregnancy
  • Elevations seen as early as the day of the expected menstrual period (~2 weeks after fertilization)
  • Guidelines for serum hCG levels (approximate)

    Length of Time from  Last Menstrual Period  (Gestational Age)	hCG  Concentration
    3 weeks	5-50 mIU/mL
    4 weeks	5-426 mIU/mL
    5 weeks	18-7,340 mIU/mL
    6 weeks	1,080-56,500 mIU/mL
    7-8 weeks	7,650-229,000 mIU/mL
    9-12 weeks	25,700-288,000 mIU/mL
    13-16 weeks	13,300-254,000 mIU/mL
    17-24 weeks	4,060-165,400 mIU/mL
    25-40 weeks	3,640-117,000 mIU/mL

• Synthesis by malignancies
  • Synthesized by placental trophoblastic cells in gestational trophoblastic tumors and some germ cell tumors
  • Germ cell tumors may produce hCGβ only
• Synthesis by pituitary
  • Most common after menopause when sex steroids are decreased
  • Pituitary is hyperstimulated to produce FSH and LH
  • Hyperstimulation may cause synthesis of hCG

Clinical Presentation

• Clinical uses of hCG tests
  • Determine or rule out pregnancy
  • Diagnose ectopic pregnancy
  • Tumor marker (see gestational trophoblastic disease and testicular cancer)
  • Down syndrome screening (see prenatal screening)

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Beta-hCG, Urine Qualitative 0020229 Method: Immunoassay	Rule out pregnancy
Beta-hCG, Quantitative (Tumor Marker), CSF 0020730 Method: Quantitative Electrochemiluminescent Immunoassay