Dubiously increased FT4 and FT3 levels in clinically euthyroid patients: clinical finding or analytical pitfall?

OBJECTIVES: We systematically investigated normally or subclinically increased thyroid stimulating hormone (TSH) values associated with unexpectedly increased thyroxine (FT4) and free triiodothyronine (FT3) in findings of patients without any thyroid disease. Moreover, we looked for alternatives to overcome such states with an improved diagnostic procedure and to investigate the pathogenetic background of the respective patients. METHODS: Samples with TSH concentrations within the range of 0.4-10 mU/L combined with increased concentrations of FT4 (n=120; Cobas, Roche) were collected over a period of around six years. Cobas FT4 results were compared with measurements from Liaison (DiaSorin) and Architect (Abbott) FT4 assays. For further validation all samples were measured for total thyroxine (TT4) (Cobas, Roche). Finally, FT3 and TT3 as complementary parameters were measured in samples with leftover material. To overcome potential analytical disturbances from stimulating heterophilic antibodies, we used heterophilic blocking tubes (HBTs). RESULTS: From the 120 samples with increased FT4 concentrations by Cobas, 51/120 were also increased by Liaison, and 26/120 by Architect. However, the measurement of TT4 indicated only n=10/120 increased values. The number of increased FT3 (n=71) measurements was higher in Architect>Cobas>Liaison (28>27>9). TT3 levels of 70/71 samples were within the reference interval. HBTs were inappropriate to reduce unspecific immunoreactivity in our samples. No clear pathogenetic background could be elucidated in the anamnesis of individual patients. CONCLUSIONS: To overcome dubious constellations of TSH, FT4, and FT3, it is helpful to measure TT4 and TT3 for control or to use an immunoassay with an alternative assay design for the respective parameters.

Procalcitonin measured by three different assays is an excellent tumor marker for the follow-up of patients with medullary thyroid carcinoma.

OBJECTIVES: Procalcitonin (PCT) has been suggested as a tumor marker in patients with medullary thyroid carcinoma (MTC). Clinical application data in long term follow-up are missing. METHODS: 210 serum samples of 169 consecutive patients with MTC (92 sporadic, 77 hereditary, 158 postoperative follow-up, 11 preoperative) were collected between 2018 and 2020. Postoperative patients were stratified into three groups according to their disease status at the end of follow-up: cured (n=51, calcitonin (CT) levels < limit of quantitation), minimal residual disease (n=55, detectable CT and no metastases provable by imaging methods), metastatic disease (n=52). In five patients CT and PCT were measured while on therapy with tyrosine kinase inhibitors (TKI). CT was analyzed by the Roche ECLIA, PCT by three assays from Roche, PES, Abbott. RESULTS: The mean ± SD values seen with the three PCT assays in the MTC response groups, cured: <0.06, 0.016 ± 0.007, 0.014 ± 0.007 ng/mL, minimal residual disease: 0.511 ± 0.800, 0.389 ± 0.687, 0.341 ± 0.614 ng/mL, metastatic disease 109 ± 202, 60.4 ± 110, 63.3 ± 115 ng/mL correlate well with the CT results in these groups: cured <1.0 pg/mL, minimal residual disease 91.3 ± 121.5 pg/mL, metastatic disease 14,489 ± 30,772 pg/mL. There was a significant correlation (p<0.001) between the three PCT assays (Roche/PES r=0.970, Roche/Abbott r=0.976, Abbott/PES r=0.995). In the course of treatment with TKI both CT and PCT reflected clinical state. Preoperative PCT in hereditary MTC has the same diagnostic validity than CT. CONCLUSIONS: PCT measured with three different immunoassays is as good as the standard tumor marker CT in the follow-up of MTC but has a superior analytical stability.

Analytical evaluation of a BNP assay on the new point-of-care platform respons®IQ.

a) Objectives: respons®IQ is a new point-of-care (POC) immunoassay platform utilizing evanescent field total internal reflection fluorescence (TIRF) detection and active microfluidics controlled by optical sensors. A B-type natriuretic peptide (BNP) assay was developed on this system. The objective was to show that the BNP test fulfils the basic requirements regarding analytical performance, storage stability of cartridges and correlation to reference systems to be used as a POC test. b) Design and methods: Analytical sensitivity and imprecision were determined in 10 separate experiments over a period of one year. Cartridge storage stability at 4-7 °C and 37 °C was tested. The correlation of responsIQ whole blood measurements to a POC reference device and a laboratory analyzer was determined using 100 patient samples. c) Results: Limit of detection (LOD) was 2.3±1.0 pg/ml BNP and within-run coefficient of variation (within-run CV) was 4.8±1.4% down to a concentration of <40 pg/ml BNP. Cartridge storage stability at 4-7 °C was greater than 50 weeks and at 37 °C, stability was three weeks. The correlation of responsIQ results with both reference methods was high (r≥0.972). d) Conclusions: The developed BNP test fulfils the basic requirements for the performance parameters defined above. The test׳s sensitivity was in the performance range of laboratory analyzer BNP tests. This is the first extensive proof of concept of the responsIQ system.