Assays / Hormones / Human Chorionic Gonadotrophin - b-hCG (CSF, serum, urine)

Clinical use
1 Diagnosis of choriocarcinoma and germ cell tumours of the ovary, testis or mediastinum and monitoring response to therapy.

2 Monitoring other rare cancers which produce this gonadotrophin ectopically.

3 Detection of metastases to the brain from choriocarcinoma or germ cell tumours.

Applications
When hCG is used to diagnose early pregnancy, the concentration will double in approximately 48h. In both trophoblastic tumours and ectopic pregnancies, there is a slower rise with hCG values lower than for a comparable stage of normal pregnancy. A fall in concentration will suggest a failing pregnancy or miscarriage.

Patients confirmed as having a hydatidiform mole should be registered with the appropriate follow-up Centre (Charing Cross Hospital, London or Royal Hallamshire Hospital, Sheffield).

1,2 Trophoblastic disease and germ cell tumours.

In these conditions hCG may be secreted as the intact dimer, free b-subunit or fragments such as b-core fragment (which is cleared very rapidly from serum and detectable only in urine). In addition, the b -subunit may be "nicked" i.e. lose specific sections of the peptide chain and the C-terminal may be missing altogether. These changes will affect most commercial assays which were developed principally for measuring hCG in pregnancy and which require two unaltered epitopes to complete the "sandwich".

The antibody used in this radioimmunoassay is directed to a single epitope on the b -subunit, detects both free b, intact hCG and b-core fragment, is not affected by "nicks" and cross-reacts less than 0.25% with luteinising hormone of pituitary origin.

Secretion of hCG declines during successful therapy; renewed secretion provides evidence of recurrence.

3 Cerebral metastases.

Intracerebral tumours secreting hCG can be detected from comparison of b -hCG concentrations in peripheral serum and cerebro-spinal fluid.

Patient Preparation
None.

1,2 Diagnosis of germ cell tumours or ectopic production of hCG.

Take blood (5 mL). For management of these conditions, take blood (5 mL) before surgery or therapy and within 3 days of initiation of treatment and at regular intervals during follow-up.

3 Cerebral metastases.

Take peripheral blood (5 mL) and cerebro-spinal fluid (2 mL).

Patients registered for the hydatidiform mole follow-up service will be instructed to collect blood and/or urine at the required intervals. Containers and instructions will be provided.

Sample Preparation
Serum: Collect serum and store at -20C.

Urine: Collect urine from an early morning voiding in the tube provided, which contains merthiolate (final concentration 0.01% w/v). Store at -20C.

Cerebro-spinal fluid: Collect without anticoagulant. Store at -20C.

Send serum (not less than 1 mL), cerebro-spinal fluid (2 mL) or urine (2 mL) to the SAS laboratory. Record on the SAS request form the clinical details and an estimate of the hCG level if known (to facilitate dilution and avoid unnecessary delay).

Reference Ranges
Adult males or non-pregnant females:

Serum: <5 IU/L;

Urine: <25 IU/L;

CSF: <5 IU/L.

In the absence of brain metastases, the ratio of hCG concentrations in serum and CSF is >60:1 (mean 280:1). Ratios of <60:1 are highly suggestive of the presence of intracerebral tumour tissue secreting hCG, unless serum hCG is falling rapidly in response to therapy.

Centres offering this assay
London (Charing Cross).

References
Cole LA, Kohorn EI and Kim GS. Detecting and monitoring trophoblastic disease. J Reprod Med 1994; 39: 193-200.

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