‘Hypercobalaminuria’ – Is urinary cobalamin loss a potential determinant of parenteral cobalamin (B12) efficacy in Pernicious Anaemia?

• Many patients with PA are dissatisfied with 2–3 monthly cobalamin replacement regimens. • The reasons for requesting more frequent injections are currently unknown. • Excess urinary cobalamin losses in certain individuals may explain poor treatment responses. • The hypothesis is testable by determining urinary cobalamin losses in deficient individuals. It is unknown why many patients with pernicious anaemia are satisfactorily treated with injections of hydroxocobalamin or cyanocobalamin every 1–3 months whereas others require far more frequent replacement regimens, sometimes even weekly. A substantial but inconstant fraction of an injected dose of cobalamin is excreted in the urine within 72 h of injection, with subsequent loss of variable smaller amounts. We hypothesize the existence of ‘hypercobalaminuria’, whereby increased urinary cobalamin losses constitute a currently unrecognized factor influencing treatment refractoriness in some individuals. The hypothesis is testable by comparing cobalamin urinary losses in patients needing frequent as opposed to 1–3-monthly injections of cobalamin to remain symptom free. It implies that ‘less-responsive’ patients are likely to have significant hypercobalaminuria.