From the Guidelines
A negative serum pregnancy test with a positive urine pregnancy test and beta hCG can occur due to the limitations of serum hCG assays in detecting all forms of beta hCG, particularly in cases where the beta hCG is fragmented or hyperglycosylated, as seen in certain pregnancy-related conditions or cancers 1. This discrepancy can lead to false-negative results in serum tests. According to the most recent evidence, a positive urine hCG can be helpful in excluding a false-positive serum result, as cross-reactive molecules in the blood that cause false positives rarely get into the urine 1. Other potential causes of this discrepancy include laboratory error, timing discrepancies between tests, or the use of different testing methods with varying sensitivities.
- The hook effect, which occurs when extremely high levels of hCG overwhelm the testing system, is another possible cause, typically seen in conditions like molar pregnancies or multiple gestations where hCG levels are exceptionally elevated.
- To resolve this issue, the laboratory can dilute the serum sample, which reduces hCG concentration and allows for accurate detection.
- Understanding the specific cause of the discrepancy is crucial for proper clinical management, especially if there are concerns about ectopic pregnancy or gestational trophoblastic disease, and a repeat serum test with dilution may be necessary to confirm the pregnancy status. In clinical practice, it is essential to consider the limitations of hCG assays and the potential for false-negative results, and to use a combination of serum and urine tests to confirm pregnancy status, as recommended by recent guidelines 1.
From the Research
Discrepancy between Serum and Urine Pregnancy Tests
- A negative serum pregnancy test with a positive urine pregnancy test and beta hCG can occur due to several factors, including:
- Early gestational age, where the hCG levels may not be high enough to be detected by the serum test 2
- β-core hook effects, where high levels of hCG can cause a false-negative result in urine tests 2
- Interfering substances, such as rheumatoid factor, which can cause a false-positive result in urine tests 3
- Heterophilic antibodies, which can bind to the hCG antibody in the test and cause a false-positive result 3
- Hemoglobin in the urine, although this is unlikely to cause a false-positive result 4
Analytical and Clinical Aspects of hCG Measurement
- The measurement of hCG can be useful in diagnosing pregnancy, but there are limitations to assessing hCG in urine and serum 5
- hCG exists in biological fluids as a mixture of different isoforms, which can affect the accuracy of the test results 5
- Serum hCG tests are generally more sensitive than urine tests, but urine tests are often used as a screening tool due to their convenience and rapid results 6, 2
Clinical Implications
- False-negative urine hCG test results can have serious consequences for patient management, and it is essential to confirm a suspected false-negative result with a quantitative serum hCG test 2
- False-positive urine hCG test results can also occur, and it is crucial to investigate the cause of the discrepancy and confirm the result with a quantitative serum hCG test 4, 3