integration of peripheral and glandular regulation of triiodothyronine production by thyrotropin in untreated and thyroxinetreated subjects the objective of the study was to evaluate the roles of central and peripheral t3 regulation in a prospective study involving 1796 patients the equilibria between ft3 and tsh were compared in untreated and lt4treated patients with varying functional states residual thyroid secretory capacities and magnitudes of tsh stimulation t3 concentrations were stable over wide variations in tsh levels from 02 to 7mul and endogenous t4 production in untreated patients but unbalanced in lt4treated athyreotic patients where t3 correlated with exogenous t4 supply t3 stability was related to tshstimulated deiodinase activity by clinical observation as predicted by theoretical modelling deiodinase activity in treated patients was reduced due to both diminished responsiveness to tsh and lack of thyroidal capacity deiodinase activity was increased in high thyroid volume compared to lower volumes in euthyroid patients 5ml p0001 while deiodinase differed between euthyroid and subclinically hypothyroid patients in high volume 267nmols 236 292 n214 vs 289nmols 267 315 n20 p002 it was equivalent between the 2 functional groups in low volume 233nmols 213 261 n117 vs 246nmols 222 275 n38 p022 these findings suggest that the thyroid gland and peripheral tissues are integrated in the physiological process of t3 homeostasis in humans via a feedforward tsh motif which coordinates peripheral and central regulatory mechanisms regulatory and capacity deficiencies collectively impair t3 homeostasis in lt4treated patients