Solving the Mysteries of hCG testing

Sometimes, human chorionic gonadotropin (hCG) assays don’t deliver the results they should. To explore the mysteries behind perplexing test results—and how to investigate such results, laboratorians should sign up for “Solving hCG Testing Mysteries: Challenging Case Studies for the Clinical Lab,” an AACC-sponsored webinar on Oct. 8.

The hCG assay is a widely used basic test for pregnancy. Yet, hCG tests can present issues for doctors and laboratorians if it yields an inconsistent or unexpected result. Two speakers, Ann M. Gronowski, PhD, professor of pathology and immunology and obstetrics and gynecology at Washington University School of Medicine, and David G. Grenache, PhD, professor of pathology at the University of Utah School of Medicine, plan to enlighten labs on how they can use detective work to solve the mysteries that surround perplexing hCG test results.

A number of analytical and preanalytical variables can affect hCG test results, the speakers told CLN Stat. “Very high concentrations of intact hCG and hCG beta core fragment are known to cause false negative results in certain hCG tests due to the hook effect or variant hook effect, respectively. Also, because hCG immunoassays utilize two antibodies, they are subject to false positive results due to heterophile antibody interference,” Gronowski and Grenache stated.

Sample mix-ups, especially in point-of-care testing settings, or dilute urine samples are common examples of preanalytical sources of error with hCG tests.

In addition, there are limitations to what hCG tests can do. There are instances in which they could miss a pregnancy—or yield a positive test when a pregnancy doesn’t exist.

As an example, “hCG tests can only detect pregnancy after implantation of the fertilized egg occurs and even then, only after serum (or urine) concentrations get high enough to be detected by the assay,” Grenache and Gronowski explained. This means the hCG test could miss a positive result in the event of a very early pregnancy or if very dilute urine is used.

hCG is normally produced during pregnancy, which makes it a useful marker of pregnancy status. But it’s important to note that hCG tests don't detect pregnancy—they detect hCG, the speakers emphasized. hCG can also be present in conditions other than pregnancy, including some malignancies and in postmenopausal women.

This could result in a “pregnancy test” yielding a positive result in absence of a pregnancy.

“We think it is important to be familiar with the most common causes of false and inconsistent hCG results and what can be done to investigate such results,” the speakers said.