Differential Diagnosis for High Calcium, Low PTH, and Slightly High IgM with Serum IFE

• Single Most Likely Diagnosis
  • Multiple Myeloma: This condition is characterized by high calcium levels due to bone destruction, low PTH as the parathyroid glands are suppressed by the high calcium, and an abnormal serum protein electrophoresis (IFE) which can show a monoclonal spike, often associated with an elevated IgM or other immunoglobulins.
• Other Likely Diagnoses
  • Lymphoma: Certain types of lymphoma can cause hypercalcemia and have abnormal immunoglobulin levels, including IgM. The low PTH suggests that the hypercalcemia is not due to primary hyperparathyroidism.
  • Waldenström's Macroglobulinemia: A type of non-Hodgkin lymphoma characterized by high levels of IgM, which can lead to hyperviscosity syndrome and other complications. Hypercalcemia can occur due to bone involvement.
  • Familial Hypocalciuric Hypercalcemia (FHH): Although PTH levels might be expected to be high, some variants can present with low PTH and high calcium due to altered calcium sensing by the parathyroid glands and kidneys.
• Do Not Miss Diagnoses
  • Vitamin D Intoxication: Can cause hypercalcemia with suppressed PTH. Although IgM levels are not directly affected, the clinical presentation could overlap, making it crucial not to miss this potentially reversible cause.
  • Hypercalcemia of Malignancy (not related to myeloma or lymphoma): Certain cancers can produce PTH-related protein (PTHrP), leading to hypercalcemia. However, the presence of low PTH and specific tumor markers or clinical context would guide this diagnosis.
• Rare Diagnoses
  • Sarcoidosis: Can cause hypercalcemia due to increased vitamin D conversion to its active form, but PTH is usually low. It's less likely to cause significant IgM elevation but can be associated with various immunoglobulin abnormalities.
  • Other rare lymphoproliferative disorders: Such as heavy chain disease or gamma heavy chain disease, which can present with abnormal immunoglobulin levels and systemic symptoms, including hypercalcemia.