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What tests do I order if I have a patient with high total protein levels in serum and normal or low albumin levels?

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Key concept

The cardinal feature of plasma cell disorders is the abnormal increased production of monoclonal antibodies. Thus, abnormal elevation of serum proteins should always raise suspicion of a plasma cell neoplasia.

Clinical scenario

A 65-year-old woman presents with a history of anemia of recent onset. A complete physical examination is unrevealing. Complete blood chemistry shows an elevated total protein. Serum albumin is normal. Serum electrophoresis is ordered.

Action item
  • Order a serum electrophoresis, a serum immune-electrophoresis, and a urine spot for Bence-Jones protein


Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accounts for 1.8% of all cancers and ~17% of all hematological malignancies in the United States. It is most frequently diagnosed among people aged 65–74 years, with the median age being 69 years. The American Cancer Society has estimated close to 30,000 cases of myeloma newly diagnosed in 2017. The approximate death rate is 12,000 deaths per year.1 For a patient to be diagnosed with MM, they must have not only a plasma cell disorder but also end-organ damage attributable to the plasma cell disorder. This includes at least one of the CRAB criteria (hyper-Calcemia, Renal disease, Anemia, and Bone disease) classically used to define symptomatic MM. Anemia occurs in 73% of patients. Bone pain is common (60% of patients), and 50% of patients have an elevated serum creatinine. Renal disease results from light precipitated complexes obstructing the distal convoluted tubules. Other causes of renal disease include nephrocalcinosis, amyloidosis, heavy-chain disease, and light-chain disease. Hypercalcemia >11 mg/dL is present in 10% of patients. This requires hydration with isotonic saline and bisphosphonate therapy with zoledronic acid or pamidronate in moderate or severe cases. Calcitonin can also be used to rapidly reduce serum calcium levels. Other symptoms include fatigue (32%) and weight loss (20%). Because of immune dysfunction, patients are at risk for infections. About 7%–18% of patients may present with extramedullary plasmacytomas. Less common symptoms include fever, splenomegaly, hepatomegaly, and lymphadenopathy.

  • If there is elevated serum protein, the critical differentiation to be made is whether the elevation is associated with a monoclonal gammopathy or is a nonspecific elevation of the gamma region associated with a chronic inflammatory process

  1. Kyle Ra, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33.

What is the difference between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM)?

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Key concept

MM is always preceded by a gammopathy of either undetermined significance or a state of evident progression and transformation to a myelomatous state without end organ damage, or what is known as “smoldering MM.” ...

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