Heterophilic antibodies causing falsely high serum calcitonin values

Area of Science:

• Endocrinology
• Immunology
• Oncology

Background:

• Calcitonin (CT) is a tumor marker for medullary thyroid carcinoma (MTC).
• Immunoassays can be affected by heterophilic antibodies (HA), leading to inaccurate results.
• Falsely elevated CT levels can lead to misdiagnosis and unnecessary interventions.

Observation:

• Four patients with thyroid nodules presented with falsely elevated serum CT levels due to HA.
• Three patients underwent unnecessary surgery based on erroneous MTC diagnosis.
• Clinical suspicion arose from minimal CT response to stimulation tests and lack of serial dilution linearity.

Findings:

• Interference from HA was confirmed by lack of serial dilution linearity in the CT assay.
• Addition of mouse gamma globulin and use of a polyclonal radioimmunoassay normalized CT values in some cases.
• Heterophilic Blocking Tubes (HBT) successfully eliminated the false CT immunoreactivity, confirming HA interference.

Implications:

• Clinicians should consider HA interference in cases of unexplained high CT levels, especially with minimal stimulation response or autoimmune thyroiditis.
• Accurate interpretation of CT tumor marker levels requires awareness of potential immunoassay interference.
• Implementing specific blocking or alternative assays can prevent misdiagnosis and inappropriate patient management for MTC.