HCG measurement (pregnancy testing) in the emergency room – an interesting case history

Human chorionic gonadptrophin (HCG) is a hormone composed of two dissimilar sub-units (a and b) that is normally only produced in measurable quantities by synctiotrophoblastic (placental) cells during pregnancy. Pregnancy testing is based on measurement of the concentration HCG in urine or blood serum.   

Blood levels begin to rise from <5mIU/mL at the time of uterine implantation, that is around 8-10 days after conception, increasing rapidly to maximium level (~ 120,000 -150,00 mIU/mL) at around 10 weeks gestation before falling back to around 15,000-20,000 mIU/mL for the remaining 30 weeks of pregnancy. 

The principle use of HCG testing in an emergency setting is the early diagnosis of pregnancy (HCG < 5mIU/mL excludes pregnancy).  As a recently published case-study report highlights, it is also useful for diagnosis of some pregnancy-related disorders including hydatidiform mole (molar pregnancy). 

Hydatidiform mole is a benign tumour of placental origin that results from an abnormal fertilised egg (zygote) and subsequent abnormal proliferation of the trophoblastic cells of the growing but ultimately non-viable ‘fetus’ that synthesize HCG. A molar pregnancy is thus associated with HCG level considerably higher than would be expected during a normal pregnancy of the same gestational age.    

The case concerns a 47 year-old pregnant lady. Based on the date of her last menstrual period, estimated gestational age was 11 weeks and 3 days.  She attended the emergency room because of recent onset of vaginal bleeding and abdominal pain.  

Qualitative urine HCG testing at triage was curiously negative indicating that the patient was not in fact pregnant, but serum HCG testing revealed an extremely high level (1,094,950 mIU/mL).  Based on presenting symptoms, serum hCG concentration and appearance of uterus on ultrasound scan, a diagnosis of molar pregnancy was made and the patient was sent for urgent surgical treatment (cervical dilation and vacuum extraction of uterine contents). 

Subsequent pathological examination of the recovered tissue confirmed a partial hydatidiform mole. 

Since the serum HCG was extremely high it must be assumed that the qualitative urine pregnancy  (HCG) test was falsely negative, and discussion by the authors focuses on this aspect of the case history.  They suggest two equally feasible explanations for the urine test being falsely negative.  Both explanations relate to the fact that assays for HCG are based on detection of antigen (HCG) by antibody (anti-HCG); they are immunoassays. 

The first explanation is the so called ‘hook effect’ that can affect any immunoassay, and arises if the antigen being detected is present in excess of the detecting antibody.   

Serial dilution of the urine sample (and therefore the concentration of HCG) before the assay provides the evidence that the ‘hook-effect’ is operating and also, after taking into account the dilution, the true concentration of HCG in the urine. 

The second explanation is based on the fact that the urine of patients with hydatidiform mole may contain high concentration of ‘abnormal’ HCG degradation products that are not necessarily detected by the detecting antibody system.  

A simple take home message of this second explanation is that not all pregnancy HCG assay systems are equal in their ability to diagnose hydatidiform mole. It is important to be aware of the limitations of the HCG assay being used.