MON-197 Discordant Serum and Urine hCG in a Postmenopausal Woman: Diagnostic Pitfalls and the Role of Assay Interference

Abstract Disclosure: A.N. Mukhtar: None. M.J. Chehade: None. C.A. Koch: None. Background: Elevated human chorionic gonadotropin (hCG) in postmenopausal women is uncommon and often raises concerns about malignancy. However, benign causes such as pituitary hCG secretion and assay interference must be considered. This case highlights the diagnostic complexities arising from assay variability and discordant serum-urine hCG results. Case Presentation: A 50-year-old postmenopausal woman with a history of squamous cell skin cancer, hysterectomy for endometriosis, and empty sella presented with recurrent headaches. Routine serum hCG testing for imaging purposes revealed a level of 6 mIU/mL while on estrogen replacement. Tumor markers (CA 125, CA 19-9, CEA, inhibin B, AFP) were normal, and rheumatoid factor was negative. In August 2023, after discontinuing estrogen, serum hCG measured 8 mIU/mL, within the postmenopausal reference range (<10 mIU/mL), yet a urine pregnancy test was positive. By July 2024, serum hCG had risen to 10 mIU/mL. Imaging ruled out malignancy but revealed pituitary gland inhomogeneity and a left adrenal myelolipoma. The discrepancy between urine and serum hCG results, in the absence of malignancy, suggested assay interference. Conclusion: This case underscores the diagnostic challenges of interpreting mild hCG elevations in postmenopausal women. Urine pregnancy tests can detect hCG at thresholds of 20–25 mIU/mL, indicating possible variability in hCG isoforms excreted in urine. The discordant serum and urine results, combined with the absence of malignancy, suggest assay interference as the most likely explanation rather than a neoplastic cause. Mechanisms such as heterophilic antibodies or cross-reactivity with other glycoproteins may contribute to false elevations.The case highlights the importance of recognizing assay limitations and the need for serial testing and alternative assay confirmation when encountering unexpected hCG elevations. Clinicians should be aware of these diagnostic pitfalls and collaborate with laboratory specialists to improve assay standardization. In some cases, hormonal therapy to suppress pituitary-derived hCG may be a viable management strategy. Ultimately, a comprehensive evaluation, including tumor marker testing and imaging, remains essential to rule out malignancy and avoid unnecessary interventions. Presentation: Monday, July 14, 2025