Objective: To examine the properties of the unique degraded forms of hCG produced in familial hCG syndrome and to describe 15 cases referred to the USA hCG Reference Service.
Study design: Total hCG was detected by Immulite total hCG assay. The molecules missing the beta-subunit C-terminal peptide were detected by the Centaur total hCG assay; the proportion of molecules missing the beta-subunit C-terminal peptide was determined as Immu-lite assay minus Centaur assay. Free beta-subunit was detected in the FBT11 free beta-subunit assay with 5008 anticore-hCGbeta tracer.
Results: In all cases the syndrome was confirmed by either a mother,father, or sibling exhibiting ectopic hCG production. Serum hCG ranges in cases from 1-216 mIU/mL and urine hCG from 1.5-527 mIU/mL. It was estimated that 48-100% of molecules were missing the beta-subunit C-terminal peptide. Serum hCG free beta-subunit was measured, accounting for 52-79% of the total hCG immunoreactivity. Molecules missing the C-terminal peptide and free beta-subunit mark this syndrome. Serial serum samples were examined in 4 cases; hCG concentrations varied widely with time from < 1 to 182 mIU/mL.
Conclusion: The proportion of molecules missing the beta-subunit C-terminal peptide, 48-100%, is extraordinarily high. Epitope studies and gel filtration studies indicate that the C-terminal peptide may not actually be missing, suggesting that the beta-subunit may be a mutant blocking C-terminal peptide recognition.