Decreased production of vitamin B12 binding proteins, like haptocorrin, has been proposed as the mechanism for spurious low values. 5 Certain conditions or medications can also cause spurious low serum vitamin B 12 levels and thus might cause the appearance of vitamin B 12 deficiency when the patient is not deficient. Examples include multiple myeloma, HIV infection, pregnancy, oral contraceptives, and phenytoin use. An example of spuriously low vitamin B 12 level in pregnancy was demonstrated in a series of 50 pregnant individuals with low vitamin B 12 levels (45-199 pg/mL), in whom metabolite testing for MMA and homocysteine showed no correlation with vitamin B 12 level. 6
Further complicating things, some conditions can cause spuriously increased vitamin B 12 levels and thus might cause the appearance of normal vitamin B 12 levels when the patient is actually deficient. 7 Examples include occult malignancy, myeloproliferative neoplasms, alcoholic liver disease, kidney disease, and nitrous oxide exposure (the latter of which is unique in that it can also cause true vitamin B 12 deficiency, as evidenced by clinical symptoms and high MMA levels). 8,9
Lastly, autoantibodies to intrinsic factor in individuals with pernicious anemia may compete with intrinsic factor in the chemiluminescence assay and result in spuriously normal vitamin B 12 levels in the presence of true deficiency. 10-12 If the vitamin B 12 level is very high (eg, 800 pg/mL), we do not worry about this effect in the absence of clinical features suggesting vitamin B 12 deficiency; however, if the vitamin B 12 level is borderline or low-normal and/or other clinical features suggest vitamin B 12 deficiency, it is prudent to obtain other testing such as an MMA level.
Dr. Ulin:
We are also joined by Dr. Rahul Ganatra, who cared for the patient at the time the diagnosis was made. Dr. Ganatra, can you share the final diagnosis and provide an update on the patient?
Rahul Ganatra, MD, MPH, Director of Continuing Medical Education, VABHS:
The patient’s hemoglobin rose to 6.9 g/dL after transfusion of 2 units of packed red blood cells, and his dyspnea on exertion and fatigue improved. Iron studies, serum thiamine, serum folate, ADAMTS13 activity levels, and AM cortisol level were normal. Upon closer examination of the peripheral blood smear, rare hypersegmented neutrophils were noted. Serum B 12 level returned below assay (< 146 pg/mL), and serum MMA was 50,800 nmol/L, confirming the diagnosis of severe vitamin B 12 deficiency. Antibodies against intrinsic factor were detected, confirming the diagnosis of pernicious anemia. Treatment was initiated with intramuscular cyanocobalamin every other day and was transitioned to weekly dosing at the time of hospital discharge. After excluding adrenal insufficiency, his levothyroxine dose was increased. Finally, a liver mass biopsy confirmed a concomitant diagnosis of HCC. The patient was discharged home. Five weeks after discharge, his serum B 12 level rose to > 1000 pg/mL, and 10 months after discharge, his TSH fell to 0.97 uIU/mL. Several months later, he underwent stereotactic body radiotherapy for the HCC. One year after his initial presentation, he has not resumed work as a barber.