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David L Murray, Commentary, Clinical Chemistry, Volume 65, Issue 7, 1 July 2019, Pages 837–838, https://doi.org/10.1373/clinchem.2019.302901
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The authors present an illustrative case of multiple myeloma (MM) that presented as symptomatic hypercalcemia. Although hypercalcemia is part of the “CRAB” diagnostic criteria (increased calcium level, renal dysfunction, anemia, and destructive bone lesions), symptomatic hypercalcemia is not a common presentation of MM. In a study of patients presenting with MM, anemia was present initially in 73% of patients, hypercalcemia (total calcium ≥11 mg/dL) in 13%, and a serum creatinine concentration ≥2 mg/dL in 19% (1). In addition, most cases of hypercalcemia were not symptomatic but documented only on clinical suspicion of MM. Hence, it may be easy for clinicians to not associate symptomatic hypercalcemia with MM. The coexistent hyperviscosity syndrome, also a less common finding, most likely exacerbated the patient's symptoms. There are several clues presented in this case that should trigger suspicion of malignancy: the history of weight loss, symptomatic anemia, and the increased κ free light chains >100 mg/dL. As the authors point out, a decreased anion gap can also be a good clue for the presence of high concentration M protein. There are only a few causes for a decreased anion gap, with the 2 most common causes being hypoalbuminemia and high immunoglobulin concentrations. In a patient with increased total proteins, a decreased anion gap is a good indicator of an underlying plasma cell disorder. Lastly, this case highlights that MM typically presents without a prior diagnosis of monoclonal gammopathy of undermined significance when multiple studies have shown that multiple myeloma is consistently preceded by it (2).
