Misleading free t4 due to auto-t4 antibodies resulting in abnormal thyroid function tests: a case report

Introduction: The presence of elevated TSH with high free T4 is considered as an abnormal thyroid function test. This may be due to false elevation of serum T4 associated with autoantibodies to T4. We report a case that presented with high serum freeT4 and TSH associated with autoantibodies to T4 . Case presentation: A 40 year old female patient presented with tiredness and sweating. She was diagnosed with primary hypothyroidism two years ago based on elevated TSH. She was treated with thyroxine 50mcg per day for 6 months and then she was defaulted. Examination revealed a thin lady with BMI of 18.5 Kgm-2 with a mild goiter. She was otherwise clinically euthyroid. Investigations revealed abnormal thyroid function test (TFT) with TSH of 43.6mIU/l and freeT4 of 3.06ng/dl. Her TFT was repeated on three laboratories which showed elevated TSH and upper normal to elevated freeT4. She had high titres of anti thyroid peroxidase (TPO antibodies) > 1300mIU. Her thyroid scan revealed small multinodular goiter and fine needle aspiration cytology confirmed Hushimoto’s thyroiditis. In view of the clinical findings the following possibilities were considered; assay interference, TSHoma and thyroid hormone resistance. TSHoma seemed less likely due to normal pituitary gland on MRI and normal SHBG. Further analysis of the sample was done with comparison between one step and two step methods using Cantaur and Delfia assays respectively. There was no evidence of assay interference in respect of TSH (38.73 vs 44.1mIU/l) and free T3 (3.9 vs 5.3pmol/l), however the freeT4 measurements were not consistent across the two platforms (25.6 vs 11.8 pmol/l). In addition, the total T4 measurement was elevated (219nmol/l; normal range 69-141) with 32% recovery after PEG treatment. Taken together, the results were suggestive of autoimmune hypothyroidism with evidence of freeT4 (and total T4) assay interference due to anti-T4 autoantibodies. The patient was treated with thyroxine and thereafter monitored using a TSH assay alone to guide treatment adequacy. Conclusions: Clinicians must be aware of possible assay interference including the measurement of freeT4 in the differential diagnosis of abnormal TFT that do not fit the patient’s clinical presentation.