Case report: When measured free T4 and free T3 may be misleading. Interference with free thyroid hormones measurements on Roche® and Siemens® platforms

Abstract

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-T4) 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 T4 (FT4) - 6.8 ng/ml and free T3 (FT3) - 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-T4 was stopped, and this was followed by a rapid increase in TSH (to 77.76 μIU/ml) and some decrease in FT4 and FT3, however FT4 concentration remained elevated (2.1 ng/ml). Following this, L-T4 was restarted. On admission to our Department, she was clinically euthyroid on L-T4, 88 μg, once daily. Investigations on Roche® platform confirmed mildly elevated TSH - 5.14 (rr: 0.27-4.2 μIU/ml) with high FT4 [4.59 (rr: 0.93-1.7 ng/ml)] and FT3 [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 FT4 and FT3 were assessed on the day of discontinuation of L-T4 and after four days by the means of Abbott® Architect I 1000SR platform. These revealed FT4 and FT3 concentrations within the reference range [e.g., FT4 - 1.08 ng/ml (rr: 0.7-1.48)] vs 4.59 ng/ml (rr: 0.93-1.7, Roche®), FT3 - 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.ConclusionsClinicians must be aware of possible assay interference, including the measurements of FT4 and FT3 in the differential diagnosis of abnormal results of thyroid function tests that do not fit the patient clinical presentation.

Falsely undetectable TSH in a euthyroid patient

“…However, there are other studies which show free T3, freeT4 and T4 levels could be in normal range with increased or decreased serum's TSH level due to the presence of heterophilic antibodies [5,6].…”

Diagnostic Dilemma In Discordant Thyroid Function Tests Due To Thyroid Hormone Autoantibodies

“…The latter adjustment does not correct for specific assay interferences. It has been suggested that two-step methods are less prone to THAAbs interference, because the procedure ensures that there is no contact between serum components and the analog tracer (8, 9). …”

Misleading FT4 measurement: Assay-dependent antibody interference

“…However, comparison of FT4 results between different methods can be challenging ( 19 , 20 ). One should be aware of these differences between laboratory methods and use the appropriate reference intervals when interpreting results.…”