From the Guidelines
Elevated globulin levels on a comprehensive metabolic panel are a significant finding that warrants further investigation, as they may indicate underlying conditions such as chronic infections, autoimmune disorders, liver diseases, or blood cancers like multiple myeloma or lymphoma. The globulin fraction contains various proteins, including antibodies (immunoglobulins), and an increase in these proteins often reflects the body's response to disease processes. To properly evaluate elevated globulins, additional testing is typically needed, including protein electrophoresis to determine which specific globulin fractions are increased 1.
Key Considerations
- The clinical significance of elevated globulins depends on the degree of elevation, the patient's symptoms, and other laboratory findings.
- Mild elevations may occur with common inflammatory conditions, while significant elevations, especially with an abnormal albumin-to-globulin ratio, often suggest more serious underlying pathology.
- Patients with elevated globulins should follow up with their healthcare provider for appropriate evaluation rather than dismissing this as an incidental finding.
- The presence of elevated globulins can be associated with various conditions, including Waldenström's macroglobulinemia, a rare, low-grade malignancy characterized by the presence of immunoglobulin-M (IgM)-secreting clonal cells in the bone marrow 1.
Diagnostic Approach
- Protein electrophoresis is a crucial test to determine which specific globulin fractions are increased.
- Other diagnostic tests, such as serum free light chain measurement, may be useful in certain situations, such as suspected light chain amyloidosis or renal failure 1.
- A thorough clinical evaluation, including a physical examination, medical history, and laboratory tests, is essential to determine the underlying cause of elevated globulins.
Management
- The management of elevated globulins depends on the underlying cause and may involve treatment of the underlying condition, such as infection, autoimmune disorder, or cancer.
- In some cases, treatment may involve the use of novel therapeutics, such as rituximab, bortezomib, or ibrutinib, which have shown efficacy in the treatment of Waldenström's macroglobulinemia and other conditions associated with elevated globulins 1.
From the Research
Significance of Elevated Globulin Level
- An elevated globulin level on a comprehensive metabolic panel can be indicative of certain health issues, such as liver disease or inflammatory bowel disease 2, 3.
- In patients with liver dysfunction, hyperglobulinemia may represent a functional aspect of the liver, and the correlation between serum globulin level and indocyanine green (ICG) clearance suggests that hyperglobulinemia is related to a common dysfunction estimated by ICG clearance 2.
- A high globulin fraction has been found to be independently associated with greater disease severity and healthcare utilization in inflammatory bowel disease (IBD) patients, and may function as a biomarker of a more severe future disease trajectory 3.
Association with Other Health Conditions
- Elevated globulin levels have also been associated with chronic kidney disease (CKD) progression and renal outcomes in Aboriginal and Torres Strait Islander people, with low serum albumin, haemoglobin, and bilirubin found to be associated with annual decline in eGFR 4.
- However, other studies have not found a significant association between globulin levels and certain health conditions, such as electrolyte abnormalities or kidney disorders 5, 6.
Clinical Implications
- The presence of an elevated globulin level on a comprehensive metabolic panel should be considered in the context of other laboratory results and clinical findings to determine its significance and potential implications for patient care 2, 3.
- Further investigation and monitoring may be necessary to determine the underlying cause of an elevated globulin level and to assess the risk of associated health conditions 2, 3, 4.