Persistent low levels of serum hCG: please do not miss phantom hCG! (pseudohypergonadotropinemia syndrome)

Introduction: Beyond pregnancy, persistent low levels of hCG may be associated with various benign and malignant conditions, i.e. quiescent gestational trophoblastic disease (QTD), raised pituitary hCG or false positive elevation caused by circulating heterophilic antibodies. This situation requires a clinico-biological approach in order to avoid misunderstandings that could lead to inappropriate diagnostic or therapeutic attitudes.
Observation: A 23 years old woman (GOPO status) consulted his gynaecologist because of persistent abdominal pain. She was diagnosed of having trophoblastic disease on the basis of persistently positive human chorionic gonadotropin (hCG) test (Roche Modular) results, in the absence of pregnancy. Persistent low levels of hCG (around 10 U/L) were detected in her plasma. The patient underwent a trial with methotrexate chemotherapy. Abdominal pain was unrelieved whereas plasma hCG was 8.9 U/L. A serology test for Chlamydia indicated persistent infection and a course of antibiotic treatment was underwent without any relief. A laparoscopic exploration ruled out any trophoblastic residue or pelvic adherences. The patient was referred to the Endocrine Unit for further pituitary and hormonal investigations. Plasma and urine samples were sent to Biology Service to exclude a false hCG positive value. While low levels of hCG were detected in serum by assay, no significant hCG was detected in the urine (0,1 U/L). When serum was treated with HBT tube for the detection of heterophilic antibodies, hCG levels were 0.98 U/L. After mouse serum treatment, hCG was not further detected in our patient, indicating the presence of phantom hCG due to the presence of human anti mouse heterophilic antibodies.
Conclusions: Textbooks on obstetrics and gynecology emphasize the importance of plasma hCG testing in patients with trophoblastic diseases. The ability of laboratory measurements to guide the clinician appropriately in every circumstance is limited. Caution should be exercised when clinical findings and laboratory results are discordant. Current protocols for the diagnosis and treatment of trophoblastic disease should include a compulsory test for hCG in urine and a test for heterophilic antibodies when appropriate. In this case report, we demonstrated that phantom hCG, was caused by heterogenous human anti mouse antibodies.