Persistent low level hCG. four values or more of hCG plateau over at least three weeks (days 1, 7,...

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Transcript of Persistent low level hCG. four values or more of hCG plateau over at least three weeks (days 1, 7,...

  • Slide 1
  • Persistent low level hCG
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  • four values or more of hCG plateau over at least three weeks (days 1, 7, 14, and 21 rise in hCG of 10% or greater for three or more values over at least two weeks (days 1, 7, and 14) (or a rise in hCG-H >20 percent)
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  • GTN - active GTN, choriocarcinoma - quiescent GTN placental site trophoblastic tumors (PSTTs) Trophoblastic causes of low level hCG
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  • Active GTN, Choriocarcinoma Hyperglycosylated hCG (hCG-H) hCG produced by syncytiotrophoblasts (H -hCG) synthesized by cytotrophoblast
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  • the important proportion of total hCG forms absolute marker of ongoing invasion or malignancy indicated as active disease requiring therapy
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  • Use of total hCG and hCG-H(%) (hCG-H as a proportion of total hCG) to discriminate gestational trophoblastic diseases L.A. Cole et al. Gynecol Oncol 102 (2006) 151159 a Measuring hCG, no significant difference is observed between quiescent gestational trophoblastic disease or self-resolving hydatidiform mole cases (control categories) and the early choriocarcinoma/GTN cases (P > 0.05). Measuring hCG-H(%), a significant difference is observed (P < 0.0000001 and P < 0.0000001).
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  • Quiescent GTN constant, low level of hCG, at low concentrations
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  • exception potential to transform into active GTN ( choriocarcinoma, or PSTT) need to followed with frequent hCG levels(montly) - if the hCG level is rising, confirm by measuring hCG-H at least two consecutive rising hCG need therapy
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  • Placenta site trophoblastic tumor ( PSTT) - often remotely following a normal pregnancy, spontaneous abortion, or hydatidiform mole The mean interval between the occurrence of PSTT and the antecedent GTN (2 ~ 5 years) definitive diagnosis hysterectomy significantly low hCG levels < 200 mIU/ml that free subunit- useful marker
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  • Phantom hCG false positive serum hCG
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  • A useful way of identifying a false positive serum hCG result is to send the serum to tw o laboratories using different commercial as says. If the assay results vary greatly or are negative in one or both alternative tests, then a false positive hCG can be presumed
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  • Patients who have false positive hC G test results are at risk for recurre nt false positive hCG assay results. They are also at risk for other false positives, such as CA-125 and thyr oid antibodies. They should make t heir future health care providers aw are of this problem and it should be noted in their medical records
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  • Because few cytotrophoblasts are p resent, little or no hCG-H is produc ed: the ratio of hCH-H to total hCG is usually less than 2 percent
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  • Regular hCG levels are low; the leve ls are always below 212 mIU/mL wit h no more than two-fold natural vari ation over time (at least three weeks).
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  • Imaging studies will be negative sin ce total hCG 2000 mIU/mL is required befo re a tumor can be seen by magnetic resonance imaging
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  • recommend that women with quies cent disease be placed on oral contr aceptive pills and avoid pregnancy until hCG has been undetectable for six months
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  • False-positive hCG The more than 5- differences in serum hCG results with alternative immunoassays (essential criterion) The finding that dilution of samples 2- 10 times does not diluted results close to 2- 10 times varying hCG results (more than 5- times) or negative results in 3 or more hCG tests. 2. The presence of hCG in serum and absence of detectable hCG or hCG related molecule in urine 4. The finding that a heterophilic antibody blocking agent
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  • Interfering antibodies can be of 2 types: human antianimal antibodies (HAAA) or heterophile antibodies
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  • HAAAs are specific antigen and may be produced after trea tment with therapeutic antibodies or exposure to animal a ntigens Heterophile antibodies nonspecific interaction with numero us different antigens and are believed to be caused by B cells that have not completed appropriate somatic mutation These antibodies interfere with immunometric assays, leading to falsely increased results
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  • Causes of false-positive HCG results
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  • -persistently low levels of hCG to outside of pregnancy cross-reactivity with (LH)
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  • Pituitary hCG in the serum of normal men and women hCG was secreted in a pulsatile fashion that paralleled the LH in nonpregnant suppressed by estrogen and progestin therapy OCPs higher levels of hCG in postmenopausal than premenopausal cutoffs for a negative hCG 14 IU/L / 5 IU/L The level of hCG attributable to pituitary production ranges from 1 to 3 2 mIU/mL establishing the diagnosis of pituitary hCG peri- or post-menopause or BSO, with low level hCG, should take HRT or oral contraceptives if pituitary origin after 23 weeks, suppress hCG production
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  • Nongynecologic tumors with positive serum -hCG levels
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  • rule out pregnancy and ectopic pregnancy determine if the hCG is biologically real False-positive hCG - 1. the presence of hCG immunoreactivity in serumbut not urine - 2. varying hCG results (more than 5-fold) or negative results in 3 or more hCG tests - 3. the suppression of result by a heterophilic antibody blocking agent determine if active GTN, PSTT, or non-trophoblastic malignancy is present hCG-H is detectable, >1 ng/ml: active GTN/choriocarcinoma hCGfree -subunit is more than one third of hCG: PSTT or non-trophoblastic malignancy hCG-H(-) or no significant hCG free -subunit: quiescent GTD peri- or post-menopause or BSO: pituitary hCG L.A. Cole et al Gynecol Oncol 102 (2006) Guidelines for the management of patients with persistent low level hCG
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  • Thank you for your attention!