Can Anti-Rejection Drugs Cause Positive β-hCG?
No, anti-rejection (immunosuppressant) drugs do not directly cause false positive β-hCG test results. The primary causes of false-positive β-hCG are heterophilic antibodies, assay interference, and cross-reactivity with other substances—not immunosuppressive medications 1, 2.
Primary Causes of False-Positive β-hCG
The most common cause of false-positive serum β-hCG is heterophilic antibodies, particularly in individuals exposed to animal antigens 1, 2, 3. These antibodies interfere with the immunoassay used to detect β-hCG, creating spurious results that can lead to dangerous misdiagnoses 4, 5.
Key diagnostic clue: A positive serum β-hCG with a negative urine β-hCG strongly suggests heterophilic antibody interference, as these cross-reactive molecules in blood rarely appear in urine 6, 1, 3.
Other documented causes of false-positive β-hCG include:
- Assay-specific interference: Different commercial hCG assays have varying sensitivities and may detect different hCG isoforms/fragments, leading to false-positive or false-negative results 6, 1
- Pituitary hCG production: Conditions causing elevated luteinizing hormone (LH) can cross-react with some hCG assays 1, 7
- Exogenous hCG administration: From fertility treatments or other medical interventions 7
- Nontrophoblastic malignancies: Neuroendocrine tumors, bladder, kidney, lung, and other cancers can produce hCG 1, 7
Diagnostic Algorithm When β-hCG Results Don't Fit Clinical Picture
When you encounter an unexpectedly positive β-hCG in a patient on immunosuppressants (or any patient where pregnancy seems unlikely):
Obtain urine β-hCG immediately - If serum is positive but urine is negative, this confirms heterophilic antibody interference 1, 2, 3
Retest serum β-hCG using a different commercial assay - Varying assay methodologies can identify assay-specific interference 6, 1, 4
Consider serial dilutions or preabsorption techniques - These laboratory methods can detect interfering substances 2
Perform transvaginal ultrasound - To definitively rule out pregnancy or gestational trophoblastic disease 8, 9
Test with heterophile antibody blocking agent - Adding this agent to serum can exclude false positives definitively 3
Critical Clinical Pitfalls
Never initiate treatment for ectopic pregnancy or gestational trophoblastic disease based solely on elevated serum β-hCG without confirming with urine testing and imaging 1, 9. False-positive results have led to unnecessary chemotherapy, surgery, and life-threatening complications 4, 5.
When clinical findings and laboratory results are discordant, always suspect assay interference 2, 4. This is particularly important in patients with:
- Occupational or recreational exposure to animals (veterinarians, laboratory workers, pet owners) 3
- History of receiving mouse-derived monoclonal antibody therapies 3
- Persistently low-level positive β-hCG (typically 30-225 mIU/mL) without clinical pregnancy signs 3
Documentation Requirements
If a patient has confirmed false-positive β-hCG results, document this prominently in their medical record and notify them of the risk for recurrent false-positive results in future testing 2. This prevents repeated unnecessary workups and interventions.
Substances That Can Cause False-Positive Drug Screens (Not β-hCG)
Note that while certain medications can cause false-positive drug screening tests (such as pseudoephedrine, dextromethorphan, and fluoroquinolone antibiotics causing false-positive opiate or amphetamine screens) 6, this is a completely different issue from β-hCG testing and should not be confused with pregnancy testing.