Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors

• Published in: Clinical biochemistry Vol. 52; pp. 73 - 79
• Main Authors: Nome, Ragnhild V., Bjøro, Trine, Paus, Elisabeth, Bjerner, Johan, Fosså, Sophie D., Steen, Rita, Nustad, Kjell, Bolstad, Nils
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2018
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2017.11.016

Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay.
We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function.
We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels.
The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice.
•New and lower reference limits are suggested for the Elecsys hCG+β-assay with relevance to tumor diagnostics.•hCG is normally not detectable in healthy individuals without primary hypogonadism (i.e. elevated FSH and LH).•hCG is above the reference limits in 11% of patients in a cohort of tumor-free testicular cancer survivors.•The testicular cancer survivors with elevated hCG also have elevated FSH and LH indicating primary hypogonadism.•Elevated hCG without primary hypogonadism should raise suspicion of residual disease in patients with hCG-producing tumors