We present two cases with biochemistry results suggesting thyrotoxicosis, caused by laboratory artefacts.
Case 1: A 68-year-old male with type 2 diabetes was referred with weight loss. Results showed fT4 of 30.5 and TSH of 1.07, confirmed on repeat. He had no symptoms of hyperthyroidism.
Blood was sent for treatment with antibody-blocking reagents:
The results show typical interference from heterophilic antibodies (high fT3 and fT4, low TSH).
Case 2: A 57-year-old male with type 2 diabetes complained of fatigue. fT4 was 46.7, fT3 14.6 and TSH 0.41, confirmed on repeat. There were no toxic clinical signs.
In this case, heterophilic antibody interference was excluded. After blocking tubes fT4 was 43.8, fT3 15.9 and TSH 0.37. Analysis with a different immunoassay was reported as biochemically euthyroid. Investigations by the manufacturer confirmed the presence of antibodies to Ruthenium used in the immunoassay, affecting fT4, fT3 and TSH results.
Discussion: Causes of increased T4 levels with unsuppressed TSH include: TSH secreting pituitary adenomas, thyroid hormone resistance and familial dysalbuminaemic hyperthyroxinaemia. Auto-antibodies can also interfere with measurement techniques giving false results.
Auto-antibodies against T4 are associated with thyroid and non-thyroid disorders. Prevalence is higher in patients with hypo or hyperthyroidism and other autoimmune conditions. Auto-antibodies can also interfere with TSH measurement.
Heterophilic antibodies interfere with antibodies used in immunoassays causing spurious results. Human anti-mouse antibodies (HAMA) are well recognised and current assays use blocking agents that reduce, but not eliminate, interference.
Thus, when the biochemistry does not correlate clinically, extensive investigations are recommended involving close communication between clinician and biochemist.