Familial hCG syndrome: production of variable, degraded or mutant forms of hCG.

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.