Analytical comparability of thyroid-stimulating hormone and free thyroxine across capillary and venous collection matrices for remote thyroid diagnostics

Aim: To evaluate the analytical comparability of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in capillary blood samples collected using serum separator tubes compared with venous reference standards. Background: Advances in at-home blood collection have enabled individuals to monitor key reproductive hormones with clinical accuracy. However, the hydrophobic nature of serum separating gels in small-volume capillary tubes can cause matrix-related interference with certain lipophilic analytes, such as sex steroids. This study investigates whether TSH and FT4 maintain analytical integrity within this specific collection matrix, a critical requirement for ensuring the accuracy of remote thyroid diagnostics. Materials & methods: This secondary analysis, drew data from two collection events of a validated primary study: an at-home collection setting (Trial 1, capillary samples only) and a supervised clinic-based setting (Trial 2, concurrent capillary and venous samples). Samples from 39 participants were analyzed for TSH and FT4 using the Cobas ® e801 immunoassay platform (Roche Diagnostics). Statistical significance was assessed using paired t-tests on log-transformed values, with a Šidák-adjusted threshold (α = 0.000814) to account for multiple comparisons. Results: TSH and FT4 demonstrated robust analytical comparability across all seven tube-pair comparisons. Mean percentage differences for TSH ranged from -2.96% to +2.43%, and for FT4 from -1.49% to +0.50%. All differences fell substantially below the desirable total allowable error (TEa) thresholds derived from the European Federation of Clinical Chemistry and Laboratory Medicine Biological Variation Database (24.7% for TSH; 6.3% for FT4). In contrast to the pronounced gel-related suppression previously documented for estradiol (-13.3%) and testosterone (-9.0%), thyroid analytes exhibited no clinically significant matrix-related bias. Conclusion: TSH and FT4 demonstrate consistent analytical comparability across capillary serum separator tube collection matrices. These findings provide preliminary analytical evidence supporting capillary-based sampling as an alternative to venipuncture for thyroid monitoring within the pre-analytical conditions studied, and support the integration of these markers into decentralised, at-home diagnostic frameworks.