False Negative Urine Pregnancy Testing with Complete Molar Pregnancy: An Example of the Hook Effect

Gestational trophoblastic disease (GTD) encompasses a group of tumors derived from trophoblasts, which normally form the placenta during pregnancy. Human chorionic gonadotropin (hCG) is a glycoprotein composed of an alpha subunit identical to that of thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Detection of beta-hCG is achievable in both urine and serum samples, proving useful for the detection of normal pregnancy and GTD. However, in the presence of very high levels of beta-hCG, a false negative result may be obtained due to a phenomenon called the "hook effect" or "prozone phenomenon." In certain circumstances, trophoblastic tumors can produce very high levels of beta-hCG, causing misleading results on urine pregnancy testing.

A 49-year-old Caucasian female with past medical history pertinent for deep vein thrombosis, ovarian cysts, and osteopenia presented to her internist with report of irregular uterine bleeding for the preceding three months, accompanied by complaints of abdominal bloating, night sweats, and constipation. The patient stated she had completed two negative qualitative urine pregnancy tests and had been seen by both gynecology and gastroenterology, with recommendations to start supplemental estrogen for her symptoms and begin additional fiber intake for irritable bowel syndrome, respectively. Despite negative urine beta-hCG, a quantitative serum beta-hCG was obtained and revealed a level greater than 200,000 international units (IU). The patient was referred to gynecologic oncology and an open abdominal hysterectomy with preservation of her ovaries was performed. Histopathologic examination showed a complete hydatiform mole with no evidence of invasion.

The case highlights the importance of clinical judgment in modern medicine, where biochemical methods and imaging modalities have become main stays in diagnosis. As mentioned, there are ways to reduce the incidence of the hook effect, but with added time and cost. Clinicians need to consider the possibility of the hook effect for instances where the clinical picture points to a disease entity despite negative test results. Delaying diagnoses, as illustrated with GTD, has the potential to cause significant morbidity and mortality.