Empirical Thyrotropin-Free Thyroxine Relationship Across the Thyrotropin Spectrum and Implications for Reference Intervals

The TSH-FT4 relationship over the entire functional TSH range is segmented rather than uniformly log-linear, and the interval over which FT4 changes little may represent physiological homeostasis. Population-based TSH reference intervals showed partial concordance with the empirically derived homeostatic range, particularly at the upper end, whereas the lower boundary was less closely aligned. Empirically derived breakpoints and population-based reference intervals may therefore offer complementary perspectives for interpreting borderline biochemical abnormalities.