From the Guidelines
Elevated protein and globulin in serum should be worked up with a comprehensive history, physical examination, and specific laboratory tests to determine the underlying cause, with management focused on treating the primary disease rather than the laboratory abnormality itself. The initial workup should include serum protein electrophoresis (SPEP), immunofixation electrophoresis, and quantitative immunoglobulins to identify monoclonal gammopathies such as multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS) 1. Additionally, complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, and C-reactive protein should be ordered to assess for inflammation or infection.
Some key considerations in the workup include:
- Identifying autoimmune hepatitis (AIH) as a potential cause, given that increased serum c-globulin or IgG levels are found in approximately 85% of patients with AIH, even in the absence of cirrhosis 1
- Using the simplified diagnostic criteria for AIH, which includes the presence of high IgG levels, liver histology, and absence of viral hepatitis 1
- Recognizing that the range within which c-globulins and IgGs are considered normal is wide, and some patients may show apparently ‘‘normal’’ IgG levels at diagnosis but still have a relative increase in their IgG levels 1
Management of elevated protein and globulin in serum depends on the underlying cause. For inflammatory conditions such as AIH, treatment with anti-inflammatory medications and immunosuppressants is essential, with the goal of minimizing the risk of disease relapse, liver-related death or transplantation, and side effects of treatment 1. If multiple myeloma is diagnosed, treatment may include combinations of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and corticosteroids, potentially followed by stem cell transplantation in eligible patients. For chronic infections, appropriate antimicrobial therapy is indicated, and liver disease may require specific management based on etiology. Regular monitoring of protein levels is important to assess treatment response, and the elevated proteins themselves are not harmful but serve as markers of underlying pathology.
From the Research
Causes of Elevated Protein and Globulin in Serum
- Elevated protein and globulin in serum can be caused by various conditions, including malignancy 2, severe chronic liver diseases 3, and infections such as leprosy 4.
- In cancer patients, the electrophoretic pattern of serum proteins shows a decreased ratio of albumin to globulin, and increased levels of alpha(1)-, alpha(2)-, and gamma-globulins 2.
- In patients with severe chronic liver diseases, hyperglobulinemia is related to a common dysfunction estimated by ICG clearance, which represents mainly the liver's blood flow and removal capacity 3.
Workup for Elevated Protein and Globulin in Serum
- The workup for elevated protein and globulin in serum includes serum protein electrophoresis, which can help identify the type of protein elevation and guide further diagnosis 2.
- Liver function tests, including ICG clearance, can help assess liver function and identify potential liver disease as a cause of hyperglobulinemia 3.
- In patients with suspected malignancy, further workup may include imaging studies, biopsies, and other diagnostic tests to confirm the presence of cancer 2.
Management of Elevated Protein and Globulin in Serum
- The management of elevated protein and globulin in serum depends on the underlying cause and may involve treatment of the underlying condition, such as cancer or liver disease 2, 3.
- In patients with hyperglobulinemia due to liver disease, management may involve measures to improve liver function and reduce globulin levels, such as medications to enhance liver blood flow and removal capacity 3.
- In patients with malignancy, management may involve chemotherapy, radiation therapy, or other treatments to reduce tumor burden and alleviate symptoms 2.