Case report: When measured free T(4) and free T(3) may be misleading. Interference with free thyroid hormones measurements on Roche® and Siemens® platforms

A 59-year old female patient presented with apathy and 6 kg weight gain. Investigations revealed severe primary hypothyroidism (TSH>100 μIU/ml). L-thyroxine (L-T(4)) was started and titrated up to 75 μg, once daily, with clinical improvement. Other investigations revealed very high titres of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies. After three months, there was a fall in TSH to 12.74 μIU/ml, however, with unexpectedly high free T(4) (FT(4)) - 6.8 ng/ml and free T(3) (FT(3)) - 6.7 pg/ml concentrations [reference range (rr): 0.8-1.9 ng/ml and 1.5-4.1 pg/ml (Siemens®), respectively]. At this stage L-T(4) was stopped, and this was followed by a rapid increase in TSH (to 77.76 μIU/ml) and some decrease in FT(4) and FT(3), however FT(4) concentration remained elevated (2.1 ng/ml). Following this, L-T(4) was restarted. On admission to our Department, she was clinically euthyroid on L-T(4), 88 μg, once daily. Investigations on Roche® platform confirmed mildly elevated TSH - 5.14 (rr: 0.27-4.2 μIU/ml) with high FT(4) [4.59 (rr: 0.93-1.7 ng/ml)] and FT(3) [4.98 (rr: 2.6-4.4 pg/ml)] concentrations. Other tests revealed hypoechogenic ultrasound pattern typical for Hashimoto thyroiditis. There was no discrepancy in calculated TSH value following TSH dilution (101% recovery). Concentrations of FT(4) and FT(3) were assessed on the day of discontinuation of L-T(4) and after four days by the means of Abbott® Architect I 1000SR platform. These revealed FT(4) and FT(3) concentrations within the reference range [e.g., FT(4) - 1.08 ng/ml (rr: 0.7-1.48)] vs 4.59 ng/ml (rr: 0.93-1.7, Roche®), FT(3) - 3.70 pg/ml (rr: 1.71-3.71) vs 4.98 (rr: 2.6-4.4, Roche®)], confirming assay interference. Concentrations of ferritin and SHBG were normal. CONCLUSIONS: Clinicians must be aware of possible assay interference, including the measurements of FT(4) and FT(3) in the differential diagnosis of abnormal results of thyroid function tests that do not fit the patient clinical presentation.