Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment

ObjectiveWe examined the interrelationships of pituitary thyrotropin (TSH) with circulating thyroid hormones to determine whether they were expressed either invariably or conditionally and distinctively related to influences such as levothyroxine (L-T4) treatment. Design and methodsThis prospective study employing 1912 consecutive patients analyses the interacting equilibria of TSH and free triiodothyronine (FT3) and free thyroxine (FT4) in the circulation. ResultsThe complex interrelations between FT3, FT4 and TSH were modulated by age, body mass, thyroid volume, antibody status and L-T4 treatment. By group comparison and confirmation by more individual TSH-related regression, FT3 levels were significantly lower in L-T4-treated vs untreated nonhypothyroid autoimmune thyroiditis (median 46 vs 49pm, P<0001), despite lower TSH (149 vs 293mU/l, P<0001) and higher FT4 levels (168 vs 138pm, P<0001) in the treated group. Compared with disease-free controls, the FT3-TSH relationship was significantly displaced in treated patients with carcinoma, with median TSH of 021 vs 163 (P<0001) at a comparable FT3 of 50pm in the groups. Disparities were reflected by calculated deiodinase activity and remained significant even after accounting for confounding influences in a multivariable model. ConclusionsTSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.