II. Indications

  1. Pregnancy diagnosis and monitoring
  2. Antenatal Screening (Quad Screen, Aneuploidy Screening)
    1. Free bHCG is increased in Trisomy 21
    2. Free bHCG is decreased in Trisomy 18
  3. Tumor monitoring
    1. Nonseminomatous germ cell tumor monitoring
    2. Hydatiform mole diagnosis and monitoring
    3. Choriocarcinoma diagnosis and monitoring

III. Physiology

  1. HCG Function
    1. Prevents corpus luteum from involuting during pregnancy
      1. Allows for continued increase of Estrogen and Progesterone
    2. Stimulates Testosterone production in the male fetus Testes
  2. HCG is a GlycoproteinHormone with subunits a and b
    1. Composed of 65% polypeptides by molecular weight
    2. Composed of 35% large sugar side chains (8 chains)
      1. Four are N-Linked (2 each on alpha and beta)
      2. Four are O-Linked (all 4 are on beta subunit)
    3. Forms of HCG found in blood and urine
      1. Intact HCG with alpha and beta subunits
      2. Nicked HCG and nicked free beta subunit
      3. Free Beta hCG subunit and free alpha HCG subunit
      4. Hyperglycosylated free beta and free alpha subunits
      5. Beta core fragment (present only in urine)
  3. HCG shares the same alpha subunit with other Hormones
    1. Luteinizing Hormone (LH)
    2. Thyroid Stimulating Hormone (TSH)
  4. Urine and Blood HCG tests are specific for beta subunit
  5. Serum half life of HCG: 24 to 36 hours
  6. Discriminatory values at which bHCG is positive
    1. Urine bHCG: 20-25 IU/ml
    2. Serum bHCG: 10 IU/ml

IV. Interpretation: Levels of bHCG in pregnancy

  1. Estimation in pregnancy for weeks 4 to 8 (plateaus after 10 weeks)
    1. Normal pregnancy
      1. bHCG may be detectable as early as 8 days after Ovulation
      2. Typically increases 80% every 48 hours (doubling every 48 to 72 hours)
      3. Minimal expected HCG increases
        1. HCG <1500 mIU/ml: Increases at least 49% in 48 hours
        2. HCG 1500-3000 mIU/ml: Increases at least 40% in 48 hours
        3. HCG >3000 mIU/ml: Increases at least 33% in 48 hours
        4. Barnhart (2016) Obstet Gynecol 128(3): 504-11 [PubMed]
    2. Fetal demise
      1. Decreases 20% every 48 Hours
    3. Ectopic Pregnancy
      1. Slower than expected rise in bHCG
    4. Faster than expected rise in bHCG
      1. Multiple Gestation
      2. Gestational Trophoblastic Disease (extremely high bHCG)
  2. Chart of corresponding Gestational age
    1. Day 23 (3.3 weeks): 100 mIU/ml (correlates with blastocyst implantation)
    2. Day 28 (4.0 weeks): 250 mIU/ml (approximate time of first missed Menses)
    3. Day 35 (5.0 weeks): 1000 mIU/ml
      1. bHCG 1800: Gestational Sac on Transvaginal U/S
      2. bHCG 3500: Gestational Sac on Transabdominal U/S
    4. Day 42 (6.0 weeks): 4000 mIU/ml
    5. Day 49 (7.0 weeks): 15000 mIU/ml
      1. bHCG 20,000: 5-10 mm Embryo with cardiac activity
    6. Day 56 (8.0 weeks): 65000 mIU/ml
    7. Decreases gradually after 8 weeks
    8. Plateaus after 20 weeks
  3. Ranges of bHCG over each Trimester
    1. First Trimester: 30,000 to 100,000 mIU/ml
    2. Second Trimester: 10,000 to 30,000 mIU/ml
    3. Third Trimester: 5,000 to 15,000 mIU/ml

V. Efficacy

  1. Commercial Pregnancy Tests (bedside Pregnancy Test)
    1. Approved for urine and serum samples
    2. Qualitative Urine Pregnancy Test
      1. Test Sensitivity: 95%
      2. Negative Predictive Value: 98%
    3. Whole blood may also be used (e.g. Emergency Department)
      1. Wait at least 10 minutes before interpreting test
      2. Bedside whole blood method in 10 minutes
        1. Much faster than the alternative serum result from lab in over 1 hour
      3. Test Sensitivity: 96%
      4. Test Specificity: 100%
      5. Negative Predictive Value: 98%
        1. Misses cases where bHCG is <50
        2. Confirmatory testing is needed for negative tests (or repeat testing in 48-72 hours)
    4. References
      1. Fromm (2012) J Emerg Med 43(3): 478-82 [PubMed]
  2. Home Pregnancy Tests
    1. Variable efficacy after missed Menses
    2. Wide discrepancy between brands
    3. Cole (2004) Am J Obstet Gynecol 190:100-5 [PubMed]

VI. Causes: Elevated bHCG in Non-Pregnant State

  1. HCG-producing tumors in women (extremely high bHCG)
    1. Hydatidiform Mole or Choriocarcinoma (Gestational Trophoblastic Disease)
  2. HCG-producing tumors in men
    1. HCG is usually undetectable in healthy males
    2. Nonseminomatous germ cell tumor (Testicular Cancer)
      1. Used with AFP for monitoring

VII. Causes: False Positive increased serum hCG

  1. Causes
    1. Heterophilic Antibody (most common)
    2. Human anti-mouse Antibody (HAMA)
    3. Nonspecific Protein-binding hCG-like substances
    4. Red Blood Cell interference
    5. Marijuana use
    6. Hypogonadism
  2. Confirmation methods in non-pregnant conditions
    1. Qualitative urine hCG
    2. Serum hCG by different immunoassay method
    3. Serial dilutions of serum hCG sample

VIII. Causes: False Negative bHCG

  1. Dilute urine
  2. High Vitamin C intake

IX. Interpretation: HCG in Nonseminomatous germ cell tumor (Men)

  1. Interpretation
    1. Poor prognosis if bHCG >50,000 mIU/ml at diagnosis
    2. Five year survival rate: 50%
  2. Efficacy
    1. High Specificity in men
    2. Low Test Sensitivity
      1. HCG or AFP increased in 85% of patients
      2. HCG or AFP increased in only 20% of Stage 1 Cancer
  3. Protocol
    1. Initial: bHCG with AFP q1-2 months for 1 year
    2. Later: bHCG with AFP q3 months for 1 year

X. References

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Related Studies

Ontology: Pregnancy Tests (C0032976)

Definition (NCI) Any examination performed to assess if a female is gravid.
Definition (MSH) Tests to determine whether or not an individual is pregnant.
Definition (CSP) determining whether or not a female is pregnant.
Concepts Diagnostic Procedure (T060)
MSH D011258
SnomedCT 74036000
English Pregnancy Test, Test, Pregnancy, Tests, Pregnancy, PREGN TESTS, TESTS PREGN, TEST PREGN, PREGN TEST, pregnancy test (procedure), pregnancy test, pregnancy testing, Test;pregnancy, pregnancies testing, test pregnancy, tests pregnancy, pregnancy tests, pregnancies test, Pregnancy Tests, Pregnancy detection examination, Pregnancy test, PT - Pregnancy test, Pregnancy detection examination (procedure)
Swedish Graviditetstester
Japanese ニンシンハンノウ, 妊娠テスト, 診断-妊娠, 妊娠反応, 妊娠診断, 妊娠試験
Czech těhotenství - testy, Těhotenský test
Finnish Raskauskokeet
French Tests de grossesse, Diagnostic de grossesse, Test de grossesse
Polish Próby ciążowe
Hungarian Terhességi vizsgálat
Norwegian Graviditetstester, Graviditetstest
Spanish Tests de Embarazo, examen de detección del embarazo (procedimiento), examen de detección del embarazo, Prueba del embarazo, Pruebas de Embarazo
Portuguese Teste de gravidez, Testes de Gravidez
Dutch zwangerschapstest, Test, zwangerschaps-, Zwangerschapstest, Zwangerschapstests
German Schwangerschaftstest, Schwangerschaftstests
Italian Test di gravidanza

Ontology: Chorionic Gonadotropin, beta Subunit, Human (C0106132)

Definition (NCI_NCI-GLOSS) A hormone normally found in the blood and urine during pregnancy. It may also be produced by some tumor cells. An increased level of beta-human chorionic gonadotropin may be a sign of cancer of the testis, uterus, ovary, liver, stomach, pancreas, or lung. Beta-human chorionic gonadotropin may also be produced in response to certain conditions that are not cancer. Beta-human chorionic gonadotropin is being studied in the treatment of Kaposi sarcoma.
Definition (NCI) Choriogonadotropin subunit beta (165 aa, ~18 kDa) is encoded by the human CGB gene. This protein is involved in the regulation of steroid synthesis during pregnancy.
Definition (MSH) The beta subunit of human CHORIONIC GONADOTROPIN. Its structure is similar to the beta subunit of LUTEINIZING HORMONE, except for the additional 30 amino acids at the carboxy end with the associated carbohydrate residues. HCG-beta is used as a diagnostic marker for early detection of pregnancy, spontaneous abortion (ABORTION, SPONTANEOUS); ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA; or DOWN SYNDROME.
Concepts Hormone (T125) , Amino Acid, Peptide, or Protein (T116)
MSH D018997
SnomedCT 40940006
English HCG-beta, Chorionic Gonadotropin, beta Subunit, Human, HCG beta, Human Chorionic Gonadotropin, beta Subunit, Beta human chorio gonadotroph, BhCG - Beta human chorionic gonadotrophin, BhCG-Bta hum chorio gonodtroph, Hum chorio gonadtroph-fre beta, HUMAN CHORIONIC GONADOTROPIN BETA SUBUNIT, CHORIONIC GONADOTROPIN BETA SUBUNIT HUMAN, BHCG-Beta hum chorion gonadotr, Beta human chorionic gonadotropin, BHCG - Beta human chorionic gonadotropin, Human chorionic gonadotropin - free beta, Chorionic Gonadotropin, beta Subunit, Human [Chemical/Ingredient], hcg beta subunit, hcg-beta, beta subunit hcg, hcg beta, Chorionic Gonadotropin, beta Chain, Human, Chorionic Gonadotropin, beta Polypeptide, Human, HCG, beta Subunit, Chorionic Gonadotropin Chain Beta, Choriogonadotropin Subunit Beta, Chorionic Gonadotropin, Beta Chain, Chorionic Gonadotropin, Beta Polypeptide 3, Human Chorionic Gonadotropin Beta Subunit, beta-hCG, beta-human chorionic gonadotropin, HCG, beta subunit, Human chorionic gonadotropin, beta subunit, Beta human chorionic gonadotrophin, Human chorionic gonadotrophin - free beta, Human chorionic gonadotrophin, beta subunit, BHCG - Beta human chorionic gonadotrophin, Human chorionic gonadotropin, beta subunit (substance), hCG-Beta, hCGBeta, CG-Beta, CGB3, Choriogonadotropin Beta Chain, Chorionic Gonadotrophin Beta Subunit, Chorionic Gonadotropin Beta 3 Subunit, Chorionic Gonadotropin Beta Chain, Chorionic Gonadotropin Beta Polypeptide
Czech choriogonadotropin lidský - beta subjednotka, HCG-beta
Finnish HCG:n beeta-alayksikkö
French Sous-unité bêta de la gonadotrophine chorionique humaine, Sous-unité bêta de la gonadotrophine placentaire humaine, Sous-unité bêta de l'HCG, HCG-bêta, Sous-unité bêta de l'hormone chorionique gonadotrophique humaine, Chaine bêta de la gonadotrophine chorionique humaine, Chaîne bêta de la gonadotrophine chorionique humaine
Swedish Humant koriongonadotropin, beta-subenhet
Polish HCG-beta, wolna podjednostka beta ludzkiej gonadotropiny kosmówkowej, beta-hCG, Gonadotropina kosmówkowa ludzka podjednostka beta, podjednostka beta hCG, beta hCG
Japanese 性腺刺激ホルモンベータサブユニット-絨毛性-ヒト, HCG-Beta-サブユニット, 絨毛性性腺刺激ホルモンβサブユニット-ヒト, 絨毛性性腺刺激ホルモンベータサブユニット-ヒト, ヒトベータサブユニット絨毛性性腺刺激ホルモン, ヒト絨毛性性腺刺激ホルモンベータサブユニット, ベータ-HCG, ベータサブユニットヒト絨毛性性腺刺激ホルモン, ヒト絨毛性性腺刺激ホルモンβサブユニット, 性腺刺激ホルモンβサブユニット-絨毛性-ヒト
Norwegian HCG-beta, Humant choriongonadotropin, beta-subenhet, HCG-beta subenhet, Beta-HCG
Spanish HCG, subunidad beta, gonadotrofina coriónica humana, subunidad beta (sustancia), gonadotrofina coriónica humana, subunidad beta, gonadotropina coriónica humana, subunidad beta, HCG-beta, Gonadotropina Coriónica Humana de Subunidad beta
German Beta-HCG, Choriongonadotropin, Beta-Untereinheit, humanes, HCG-Beta, Humanchoriongonadotropin, Beta-Untereinheit
Portuguese Gonadotropina Coriônica Humana Subunidade beta, HCG-beta
Italian Subunità beta della gonadotropina corionica umana