Is hypokalemia (low potassium) a sign of multiple myeloma?

Low Potassium is Not a Typical Sign of Multiple Myeloma

Low potassium (hypokalemia) is not a characteristic sign or diagnostic criterion of multiple myeloma. 1, 2

Multiple Myeloma Diagnostic Criteria

Multiple myeloma is diagnosed based on the following criteria:

• ≥10% clonal plasma cells in bone marrow or biopsy-proven plasmacytoma 3
• Evidence of end-organ damage known as CRAB criteria 1, 2:
  • C: Hypercalcemia (calcium >11.5 mg/dL) 2, 4
  • R: Renal insufficiency (creatinine >2 mg/dL or creatinine clearance <40 mL/min) 1
  • A: Anemia (hemoglobin <10 g/dL) 1
  • B: Bone lesions (lytic lesions on X-ray, CT, or MRI) 1, 4

Electrolyte Abnormalities in Multiple Myeloma

Hypercalcemia

• Occurs in multiple myeloma due to increased osteoclast activity stimulated by cytokines produced by myeloma cells 4
• Considered a defining diagnostic criterion for multiple myeloma 2

Renal Involvement and Electrolyte Disturbances

• Renal impairment in multiple myeloma is primarily caused by cast nephropathy from free light chains 1
• Electrolyte abnormalities that may occur secondary to renal involvement include:
  • Hypercalcemia (as noted above) 4
  • Hyperphosphatemia in advanced renal failure 1
  • Hypophosphatemia in some cases with Fanconi syndrome 1, 5

Hypokalemia in Multiple Myeloma: Not a Primary Feature

Hypokalemia is not listed among the diagnostic criteria or typical manifestations of multiple myeloma in any of the major guidelines 1, 3, 2.

When hypokalemia does occur in multiple myeloma patients, it is typically due to:

1. Secondary effects of hypercalcemia: Severe hypercalcemia can activate calcium-sensing receptors in the thick ascending limb of Henle, leading to a hypokalemic metabolic alkalosis similar to the effect of loop diuretics 6

2. Treatment-related causes:

   • Use of loop diuretics in the management of hypercalcemia 6
   • Side effects of certain chemotherapy regimens 3

3. Rare tubular disorders: In some cases, multiple myeloma can cause Fanconi syndrome with proximal tubular dysfunction leading to electrolyte abnormalities including hypokalemia 1, 5

Unusual Presentations

While rare, there have been case reports of:

• Hypokalemic metabolic alkalosis in patients with severe hypercalcemia due to multiple myeloma 6, 7
• Fanconi syndrome with hypokalemia, hypophosphatemia, and metabolic acidosis 5
• Hyporeninemic hypoaldosteronism with hyperkalemia (not hypokalemia) 8

Clinical Implications

When evaluating a patient with hypokalemia:

• Multiple myeloma would not be high on the differential diagnosis based on hypokalemia alone 1
• If multiple myeloma is suspected, focus on the classic CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) 1, 2
• In a patient with known multiple myeloma and hypokalemia, consider secondary causes such as treatment effects or complications of hypercalcemia 6

Conclusion

Hypokalemia is not a typical sign or diagnostic criterion for multiple myeloma. The diagnosis should be based on established CRAB criteria and the presence of clonal plasma cells in the bone marrow or a biopsy-proven plasmacytoma.