hCG Testing

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

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 (testicular, ovarian)

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, 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
      • Intact hCG (dimeric)
      • Nicked hCG (hCGn)
      • Free β subunit (hCGβ)
      • Large free α
      • Nicked free β subunit (hCGβb)
      • Free αhCG
    • hCG variants in urine
      • Intact hCG (dimeric)
      • Nicked hCG (hCGn)
      • Free β subunit (hCGβ)
      • Free βhCG
      • Large free α
      • Nicked free β subunit (hCGβb)
      • Free αhCG
      • β core fragment (hCGβcf) (degradation of nicked free β)
    • 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

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

Recommended Use 

Rule out pregnancy

Measures intact hCG and hCGβ

Beta-hCG, Serum Qualitative 0020063
Method: Immunoassay

Recommended Use 

Rule out pregnancy

Limitations 

Use quantitative serum test if detection of pregnancy is critical

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

Recommended Use 

Monitor patients with hCG-secreting tumors

Measures all hCG variants

Limitations 

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

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

Recommended Use 

Rule out pregnancy

Identify pituitary hCG

General References

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

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

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

Fournier T, Guibourdenche J, Evain-Brion D. Review: hCGs: different sources of production, different glycoforms and functions. Placenta. 2015; 36 Suppl 1: S60-5. PubMed

Gronowski AM, Cervinski M, Stenman U, Woodworth A, Ashby L, Scott MG. 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 AM, Fantz CR, Parvin CA, Sokoll LJ, Wiley CL, Wener MH, Grenache DG. Use of serum FSH to identify perimenopausal women with pituitary hCG. Clin Chem. 2008; 54(4): 652-6. PubMed

Snyder JA, Haymond S, Parvin CA, Gronowski AM, Grenache DG. 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 MA, Lockwood CM, Ferguson AM, Odem RR, Stenman UH, Alfthan H, Grenache DG, Gronowski AM. 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 SP, Greene DN, Olson KN, Wiley CL, Grenache DG. Human chorionic gonadotropin discriminatory zone in ectopic pregnancy: does assay harmonization matter? Fertil Steril. 2014; 101(6): 1671-4. PubMed

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

Greene DN, Grenache DG, Education Committee of the Academy of Clinical Laboratory Physicians and Scientist. Pathology consultation on human chorionic gonadotropin testing for pregnancy assessment Am J Clin Pathol. 2015; 144(6): 830-6. PubMed

Greene DN, Petrie MS, Pyle AL, Kamer SM, Grenache DG. Performance characteristics of the Beckman Coulter total βhCG (5th IS) assay Clin Chim Acta. 2015; 439: 61-7. PubMed

Greene DN, Schmidt RL, Kamer SM, Grenache DG, Hoke C, Lorey TS. Limitations in qualitative point of care hCG tests for detecting early pregnancy. Clin Chim Acta. 2013; 415: 317-21. PubMed

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

Grenache DG. Variable accuracy of home pregnancy tests: truth in advertising Clin Chem Lab Med. 2015; 53(3): 339-41. PubMed

Gronowski AM, Grenache DG. 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

Sowder AM, Yarbrough ML, Nerenz RD, Mitsios JV, Mortensen R, Gronowski AM, Grenache DG. Analytical performance evaluation of the i-STAT Total β-human chorionic gonadotropin immunoassay Clin Chim Acta. 2015; 446: 165-70. PubMed

Medical Reviewers

Grenache, David G., PhD, Medical Director, Special Chemistry; Co-Director, Electrophoresis and Manual Endocrinology; Chief Medical Director, Clinical Chemistry at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Last Update: August 2016

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