An evaluation of simultaneously administered free and intrinsic factor bound radioactive cyanocobalamin in the diagnosis of pernicious anaemia in the elderly

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Abstract
The definitive diagnosis of pernicious anaemia (PA) in the elderly is by no means always straightforward, particularly when inappropriate medication has been introduced before the institution of specific investigatory procedures. A detailed haematological study was carried out on 301 patients aged 60-95 with a serum B12 concentration at the laboratory's lower level of normal of 150 ng per litre (Euglena gracilis assay). The diagnosis of PA was based on strict predetermined haematological criteria. All patients were subsequently studied by the simultaneous oral administration of the dual isotopes 57Co-labelled B12 bound to intrinsic factor and free 58Co-labelled B12 (Dicopac test), and urine was collected over 24 hours after an intramuscular dose of 1 mg nonradioactive B12 for estimation of the 57Co/58Co B12 ratio; 255 patients satisfied all criteria for final analysis. The Radiochemical Centre, Amersham suggests an upper limit of the normal range for the 57Co/58Co ratio of 1·3 with a lower limit for PA of 2·0. We were unable to show a sharp borderline in the 57Co/58Co B12 ratio between those patients shown by other criteria to have PA and those who do not have PA; 34% of the 71 established patients had a ratio below 2·0. From our series a ratio borderline drawn at 1·4 gave only one false negative (1·4% of the PA group). Of the 175 non-PA cases, nine (5%) gave false positive results; four of these had 58Co excretion levels high enough to make misdiagnosis unlikely. In a proportion of patients the 57Co/58Co B12 ratio was estimated at regular intervals for 36-hour periods. Maximum accuracy of isotope measurement on a single specimen was obtained 8-20 hours after isotope dosing. The Dicopac investigation is a useful simple screening test in the differential diagnosis of patients with a megaloblastic bone marrow and combined low serum B12 and folate concentrations. When carried out by the standard technique, the degree of discrimination between normal and abnormal ratios is of limited diagnostic significance in one-third of patients.