hCG Testing

Human chorionic gonadotropin (hCG) is produced at elevated levels during pregnancy as well as in gestational trophoblastic disease and due to some germ cell tumors. Additionally, hCG concentrations of a pituitary origin are sometimes detected in peri- and postmenopausal women.

Many female patients are tested for hCG before medical procedures or administration of medication that may harm a fetus. The interpretation of low-level hCG elevation in these females is problematic; such elevations might be benign or might represent malignancies such as gestational trophoblastic disease.

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Potential pregnancy
- Determine or rule out pregnancy
- Diagnose ectopic pregnancy
- Screen for Down syndrome in pregnant women (see Prenatal Screening)
Suspected gestational trophoblastic disease
Suspected testicular cancer

Laboratory Testing

Serum
- Quantitative – human chorionic gonadotropin (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 usually doubles 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 hCG β core fragment (hCGβcf)
Positive/elevated hCG
- Should be consistent with clinical picture – consider age, symptoms, etc.
  - Goal is to avoid delays in needed treatment and to identify true false positives that need no treatment
- If inconsistent, then rule out
  - False-positive hCG (interfering antibody)
    - Urine hCG
    - Serial dilution
    - Blocking agents
  - Pituitary hCG
    - Serum follicle-stimulating hormone (FSH)
      - FSH >45 mIU/mL 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)

Background

Pathophysiology

Human chorionic gonadotropin (hCG) biochemistry (basic)
- Sources of hCG
  - Pregnancy
  - Malignancy (gestational trophoblastic neoplasm, testicular cancer)
  - Pituitary origin
- 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)
  - hCGn
  - hCGβ
  - Free βhCG
  - Large free α
  - hCGβb
  - Free αhCG
  - β core fragment (hCGβcf) (degradation of nicked free β)
- Levels in serum and urine are parallel during pregnancy

Synthesis and function in pregnancy

Produced by syncytiotrophoblast cells of developing placenta
- Elevations seen as early as first day of expected menstrual period (~2 weeks after fertilization)
Functions to stimulate corpus luteum in ovary to synthesize progesterone during first weeks of pregnancy

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
Source: Cole, 2009

Synthesis by malignancies
- Produced 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 follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- Hyperstimulation may cause synthesis of hCG

ARUP Lab Tests

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

Measures intact human chorionic gonadotropin (hCG) and free β subunit (hCGβ)

Limitations

For tumor marker testing, order the beta-hCG quantitative test for tumor markers

Beta-hCG, Serum Qualitative 0020063
Method: Immunoassay

Beta-hCG, Urine Qualitative 0020229
Method: Immunoassay

Medical Experts

Genzen, Jonathan R., MD, PhD, Laboratory Section Chief, Clinical Chemistry, and Medical Director, Automated Core Laboratory, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Lehman, Christopher M., MD, Co-Medical Director, University Hospitals and Clinics Clinical Laboratory; Professor of Clinical Pathology, University of Utah

References

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

Resources 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

Educational Videos

Last Update: September 2018

hCG Testing

Diagnosis

Indications for Testing

Laboratory Testing

Imaging Studies

Differential Diagnosis

Background

Pathophysiology

ARUP Lab Tests

Medical Experts

References

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

ARUP Websites

ARUP Consult


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hCG Testing

Diagnosis

Indications for Testing

Laboratory Testing

Imaging Studies

Differential Diagnosis

Background

Pathophysiology

ARUP Lab Tests

Medical Experts

References

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

ARUP Websites

ARUP Consult