Endocrine Abstracts

Case History: We report the case of a 59-year-old lady with a persistently elevated serum thyroglobulin following a total thyroidectomy for multifocal papillary thyroid carcinoma. She subsequently underwent radioiodine therapy following which her serum thyroglobulin remained elevated. However, it was later found to be almost undetectable at 0.3 μg/l after a change in laboratory method. This discrepancy prompted further investigation, and repeat analysis using the original assay showed measurement of detectable thyroglobulin which became undetectable following treatment with a heterophilic antibody blocking tube. Thyroglobulin is frequently measured to monitor disease activity after total thyroidectomy in patients with thyroid carcinoma. All immunoassays are prone to interference, and thyroglobulin assays are susceptible to heterophile antibody (HAb) interference. HAbs have the capacity to bind to animal immunoglobulins used in immunometric assays, bridging capture and detection antibodies and lead to a false positive result in the absence of analyte. In this case our patient’s thyroglobulin remained detectable at 48 μg/l following total thyroidectomy. After discussion at the thyroid cancer multidisciplinary team meeting she was referred for radioiodine therapy. Despite this her thyroglobulin remained elevated at 47 μg/l (17/03/20). In April 2020 our laboratory changed method from the Siemens Immulite 2000 high sensitivity thyroglobulin assay to the Beckman Access high sensitivity thyroglobulin assay. Both are chemiluminescent immunometric assays. Following this change, the patient’s thyroglobulin was measured at 0.3 μg/l (21/07/20). A further sample was analysed by both methods and measured at 0.2 μg/l by Beckman assay but 27 μg/l by Siemens assay. Following pre-treatment with Heterophilic Blocking Tube (Scantibodies) containing blocking reagent, which binds and inactivates HAbs, the Siemens assay result decreased to <2 μg/l.

Conclusions and points for discussion: Heterophile antibody interference is not limited to thyroglobulin assays. Similar problems have occurred when measuring tumour markers such as human chorionic gonadotropin (hCG), leading to unnecessary adjuvant therapy for choriocarcinomas in women and testicular cancers in men. As in this case, the trend to treat thyroid cancer with radioiodine solely on the basis of high thyroglobulin levels can result in unnecessary and potentially harmful therapy for patients without actual recurrence of disease. The key learning point from this case is that when thyroglobulin elevation does not correlate with the clinical scenario then it is prudent to question the reliability of the assay and consider the presence of heterophile antibodies. It also highlights the significance of continuous communication between clinicians and biochemists in order to avoid unnecessary diagnostic procedures and treatments.