Heterophile antibodies may cause falsely lowered serum cortisol values

Area of Science:

• Clinical Chemistry
• Immunodiagnostics
• Endocrinology

Background:

• Diagnostic workup for fatigue revealed low serum cortisol and abnormal Synacthen stimulation test results.
• Initial tests suggested adrenal insufficiency in a 42-year-old woman.
• Further investigation was prompted by discrepant cortisol levels from different immunoassays during insulin hypoglycemia testing.

Observation:

• Paired serum samples from insulin hypoglycemia testing showed significantly different cortisol levels when analyzed by two distinct immunoassays.
• Plasma ACTH and overnight metyrapone testing confirmed normal hypothalamic-pituitary-adrenal axis function.
• Negative interference from a heterophile antibody in the patient's serum was identified as the cause of the initial abnormal immunoassay results.

Findings:

• Heterophile antibodies present in patient serum can cause negative interference in specific cortisol immunoassays.
• The interference led to a falsely lowered serum cortisol measurement, mimicking adrenal insufficiency.
• Confirmatory testing and immunoassay interference investigation were crucial for accurate diagnosis.

Implications:

• Failure to recognize heterophile antibody interference can lead to misdiagnosis and inappropriate clinical management.
• Awareness of potential immunoassay interference by heterophile antibodies is essential for clinicians interpreting endocrine test results.
• This case underscores the need for robust diagnostic strategies that account for analytical interferences in immunoassays.