hCG Testing

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

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 (testicularovarian)

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)
  • 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

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

Beta-hCG, Serum Quantitative 0070025
Method: Chemiluminescent Immunoassay

Beta-hCG, Serum Qualitative 0020063
Method: Immunoassay

Limitations

Use quantitative serum test if detection of pregnancy is critical

Beta-hCG, Quantitative (Tumor Marker) 0070029
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

Results obtained with different test methods or kits cannot be used interchangeably

Luteinizing Hormone and Follicle Stimulating Hormone 0070193
Method: Quantitative Electrochemiluminescent Immunoassay

Additional Tests Available

Beta-hCG, Urine Qualitative 0020229
Method: Immunoassay

Comments

Rule out pregnancy

Beta-hCG, Quantitative (Tumor Marker), CSF 0020730
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Results obtained with different test methods or kits cannot be used interchangeably

General References

Cole L, Sasaki Y, Muller C. Normal production of human chorionic gonadotropin in menopause. N Engl J Med. 2007; 356(11): 1184-6. PubMed

Cole L. hCG, five independent molecules. Clin Chim Acta. 2012; 413(1-2): 48-65. PubMed

Cole L. Human chorionic gonadotropin tests. Expert Rev Mol Diagn. 2009; 9(7): 721-47. PubMed

Gronowski A, Cervinski M, Stenman U, Woodworth A, Ashby L, Scott M. False-negative results in point-of-care qualitative human chorionic gonadotropin (hCG) devices due to excess hCGbeta core fragment. Clin Chem. 2009; 55(7): 1389-94. PubMed

Gronowski A, Fantz C, Parvin C, Sokoll L, Wiley C, Wener M, Grenache D. Use of serum FSH to identify perimenopausal women with pituitary hCG. Clin Chem. 2008; 54(4): 652-6. PubMed

Snyder J, Haymond S, Parvin C, Gronowski A, Grenache D. Diagnostic considerations in the measurement of human chorionic gonadotropin in aging women. Clin Chem. 2005; 51(10): 1830-5. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology

Cervinski M, Lockwood C, Ferguson A, Odem R, Stenman U, Alfthan H, Grenache D, Gronowski A. Qualitative point-of-care and over-the-counter urine hCG devices differentially detect the hCG variants of early pregnancy. Clin Chim Acta. 2009; 406(1-2): 81-5. PubMed

Desai D, Lu J, Wyness S, Greene D, Olson K, Wiley C, Grenache D. Human chorionic gonadotropin discriminatory zone in ectopic pregnancy: does assay harmonization matter? Fertil Steril. 2014; 101(6): 1671-4. PubMed

Furtado L, Lehman C, Thompson C, Grenache D. Should the qualitative serum pregnancy test be considered obsolete? Am J Clin Pathol. 2012; 137(2): 194-202. PubMed

Greene D, Schmidt R, Kamer S, Grenache D, Hoke C, Lorey T. Limitations in qualitative point of care hCG tests for detecting early pregnancy. Clin Chim Acta. 2013; 415: 317-21. PubMed

Grenache D, Gronowski A, Fantz C. Inappropriate use of qualitative, point-of-care urine human chorionic gonadotropin test. Am J Emerg Med. 2013; 31(6): 992-3. PubMed

Gronowski A, Grenache D. Characterization of the hCG variants recognized by different hCG immunoassays: an important step toward standardization of hCG measurements. Clin Chem. 2009; 55(8): 1447-9. PubMed

Medical Reviewers

Last Update: January 2016