Dilemma identifying Pseudohypercalcemia

Objective:
Hypercalcemia has a variety of potential causes with most common causes been primary hyperparathyroidism and malignancy accounting 90% cases. Other less common causes of hypercalcemia such as superimposed pseudohypercalcemia in the presence of increased serum total calcium concentration but normal ionized serum calcium level.

Methods:
We report the evaluation for hypercalcemia with known history of monoclonal gammopathy.

Results:
We report a case of a 71-year-old Caucasian male with history interstitial lung disease, cold agglutinin disease, and monoclonal gammopathy diagnosed in 2015 serum electrophoresis showed two M-protein at 0.33 and 0.16gm, admitted with COVID positive, found with hypercalcemia. Review of systems was pertinent for chronic fatigue and lower extremity weakness. In medication history was prednisone 20mg daily one week prior to presentation. Examination limited due to positive status. Laboratory showed Calcium Serum 10.6mg/dl, Albumin 2.3mg/dl with corrected calcium 12mg/dl (Previous Corrected Calcium in 2015 was 10.5mg/dl), PTH 83.4pg/ml (NR10-65pg/ml), Vitamin D 25-0H 46.2ng/ml (NR 30-100ng/ml), Vit D 1-25 OH 47.8pg/ml (NR 20-82pg/ml), Ionized Calcium 5.2mg/dL (NR 4.5-5.3mg/dl), TSH 0.9uIU/ml (NR 0.35-5.5uIU/ml), cortisol 19.6 mcg/dL (NR 0-20 mcg/dL) and IgM 1,690mg/dl (NR 40-230mg/dL). The patient was given IV pamidronate 60mg by medicine service. Normal ionized calcium while elevated corrected calcium in a patient with excess IgM as well as hyperparathyroidism and COVID positive setting; elevated IgM has been reported as cause of false elevated total calcium result.

Discussion/Conclusion:
Other causes of hypercalcemia can be puzzling for diagnosis. Pseudohypercalcemia in the clinical setting of M-protein disorder causes unusual calcium binding by IgM paraprotein and release of bone calcium with action of parathyroid hormone interfering with biochemical laboratory measurements. Clinicians should recognize pseudohypercalcemia as the abnormality in total serum calcium levels can be differentiated with measurement of ionized serum calcium to direct appropriate therapy to primary etiology.