Pseudohypercalcemia in Multiple Myeloma

Presentation Number: MON 319
Date of Presentation: April 3rd, 2017

Muhammad Talha*1, Rim Hasan2 and Robert S Weinstein1
1Central Arkansas Veterans Healthcare System/University of Arkansas for Medical Sciences, Little Rock, AR, 2Central Arkansas Veterans Health Care System/University of Arkansas for Medical sciences, Little Rock, AR, Little Rock, AR


Background: Hypercalcemia caused by increased bone resorption is common in multiple myeloma, resulting in suppressed PTH, bone pain and renal dysfunction. Infrequently multiple myeloma presents as pseudohypercalcemia if calcium binds to a monoclonal protein, leading to elevated total calcium but normal ionized calcium. Failure to recognize this phenomenon can leads to unnecessary investigation and treatment.

Clinical case: A 56 year old black female presented with fatigue and 40 pounds weight loss. She had high plasma viscosity, elevated serum calcium 12.6 mg/dL(8.7-10.2 mg/dL), albumin corrected calcium 13.4 mg/dL, albumin 3.0 g/dL (3.4-5.0 g/dl), total protein 10.1 g/dL (6.1-8.0 g/dL), Cr 1.2 mg/dL (0.7-1.2 mg/dL), TSH:0.66 (0.35-5.50 uU/ml), Hematocrit 31.4% (34.3-46.6%). Serum electrophoresis was suggestive of IgM gammopathy. She received IV Pamidronate 90 mg with fluids and was transferred to the myeloma institute.

Repeat labs showed serum calcium 8.9 mg/dL (8.8-10.2 mg/dL), corrected calcium 9.8 mg/dL, albumin 2.9 g/dL (3.5-5.0 g/dl), phosphorus 2.9 mg/dL (2.5-4.5 mg/dL), Mg 1.3 mg/dL (1.6-2.6 mg/dL), Cr 0.6 mg/dL (0.4-1.0 mg/dL). Serum and urine protein electrophoresis revealed M protein - IgM Kappa. Skeletal survey and PET CT did not show any focal lesions. Bone marrow biopsy showed IgM Kappa multiple myeloma.

Over 3 days, the serum calcium decreased to 7.4-8.4 mg/dL (8.8-10.2 mg/dL), with low ionized Ca 1.06 mmol/L (1.15-1.33 mmol/L). PTH was high 574.4 pg/mL (12.0-88.0 pg/mL). She was started on chemotherapy with VDT-PACE regimen. Parathyroid scan showed asymmetrically increased activity suggestive of parathyroid adenoma. Endocrinology was then consulted for further management.

Vitamin D 25-OH was low 4.5 ng/mL (30-100 ng/mL) and repeat PTH was high 285.7 pg/mL (12.0-88.0 pg/mL). However PTH at initial presentation was found to be only 26 pg/mL (14.0-66.0 pg/mL) with total Ca 12.6 mg/dL (8.7-10.2 mg/dL). Neck ultrasound showed no evidence for parathyroid adenoma. Patient was started on vitamin D replacement and oral calcium with normalization of the ionized Ca 1.21 mmol/L (1.15-1.33 mmol/L).

The initial presentation of elevated total calcium with mid normal PTH, in the absence of symptoms for hypercalcemia was pseudohypercalcemia secondary to binding of calcium with paraproteins. Subsequent ionized hypocalcaemia and hyperparathyroidism was secondary to bisphosphonate therapy in the setting of severe vitamin D deficiency.

Conclusion: Recognition of pseudohypercalcemia can prevent erroneous diagnosis, unnecessary investigations and potentially inappropriate therapy. In asymptomatic multiple myeloma patient with significant hypercalcemia, the measurement of ionized calcium is critical to exclude pseudohypercalcemia. Clinicians should be aware of that bisphosphonate therapy in this setting can produce severe ionized hypocalcemia.


Nothing to Disclose: MT, RH, RSW