How to evaluate an elevated globulin level?

From the Guidelines

Evaluating an elevated globulin level requires a comprehensive approach, starting with a thorough medical history and physical examination, followed by serum protein electrophoresis (SPEP) to identify the specific globulin fractions elevated, as the presence of high IgG levels is a distinctive feature of autoimmune hepatitis (AIH) 1. To evaluate an elevated globulin level, consider the following steps:

• Determine the degree of elevation and assess for associated symptoms
• Order SPEP to identify which specific globulin fractions are elevated (alpha-1, alpha-2, beta, or gamma)
• Additional testing should include immunofixation electrophoresis to detect monoclonal proteins, complete blood count, comprehensive metabolic panel, and inflammatory markers like ESR and CRP
• Consider specific conditions based on the pattern of elevation: polyclonal gammopathy suggests chronic inflammation, infection, or autoimmune disease, such as AIH, which is characterized by increased serum c-globulin or IgG levels in approximately 85% of patients 1
• For polyclonal elevations, evaluate for liver disease, autoimmune conditions (order ANA, RF), and chronic infections (HIV, hepatitis), as the absence of viral markers is one of the elements included in the simplified diagnostic criteria for AIH 1
• The level of immunoglobulins is an important and useful marker in monitoring the response to treatment and the achievement of remission, with normalization of both transaminase levels and IgG levels being a diagnostic marker of full biochemical remission 1
• A definitive diagnosis of AIH can be made using the simplified diagnostic criteria, which includes a score of 7 or more, with points assigned for autoantibodies, IgG or γ-globulins level, liver histology, and absence of viral hepatitis 1.

From the Research

Evaluating Elevated Globulin Level

To evaluate an elevated globulin level, several steps can be taken:

• Review the patient's medical history and perform a physical examination to identify any underlying conditions that may be contributing to the elevated globulin level 2.
• Conduct laboratory tests, such as serum protein electrophoresis and urine electrophoresis, to determine the type and amount of globulin present in the blood and urine 3.
• Check liver function tests, as liver involvement can be a cause of elevated globulin levels in multiple myeloma patients 4, 5.
• Assess for the presence of monoclonal proteins, such as immunoglobulins, which can be indicative of multiple myeloma or other plasma cell disorders 3, 6.

Laboratory Tests

Laboratory tests that can be used to evaluate elevated globulin levels include:

• Serum free light chain measurements, which can be more sensitive than urine electrophoresis for monitoring multiple myeloma 3.
• Serum and urine protein electrophoresis, which can help identify the type and amount of globulin present in the blood and urine 3.
• Liver function tests, such as AST, ALT, ALP, and γGT, which can help assess liver involvement in multiple myeloma patients 5.

Clinical Considerations

Clinical considerations when evaluating elevated globulin levels include:

• The presence of symptoms such as painless jaundice, mild pruritus, and abnormal liver function tests, which can be indicative of liver involvement in multiple myeloma 4.
• The presence of anemia, hyperuricemia, azotemia, hypercalcemia, and Bence Jones proteinuria, which can be associated with multiple myeloma 5.
• The presence of defined precursor conditions, such as monoclonal gammopathy of undetermined significance, which can increase the risk of developing multiple myeloma 6.