Horm Metab Res 2015; 47(09): 674-680
DOI: 10.1055/s-0034-1398616
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects

R. Hoermann
1  Department of Nuclear Medicine, Klinikum Luedenscheid, 58515 Luedenscheid, Germany
,
J. E. M. Midgley
2  North Lakes Clinical, Ilkley, UK
,
R. Larisch
1  Department of Nuclear Medicine, Klinikum Luedenscheid, 58515 Luedenscheid, Germany
,
J. W. Dietrich
3  Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Germany
› Author Affiliations
Further Information

Publication History

received 01 September 2014

accepted 07 January 2015

Publication Date:
06 March 2015 (eFirst)

Abstract

The objective of the study was to evaluate the roles of central and peripheral T3 regulation. In a prospective study involving 1 796 patients, the equilibria between FT3 and TSH were compared in untreated and L-T4-treated 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 0.2 to 7 mU/l) and endogenous T4 production in untreated patients, but unbalanced in L-T4-treated athyreotic patients where T3 correlated with exogenous T4 supply. T3 stability was related to TSH-stimulated 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 (<5 ml, p<0.001). While deiodinase differed between euthyroid and subclinically hypothyroid patients in high volume, 26.7 nmol/s (23.6, 29.2), n=214 vs. 28.9 nmol/s (26.7, 31.5), n=20, p=0.02, it was equivalent between the 2 functional groups in low volume, 23.3 nmol/s (21.3, 26.1), n=117 vs. 24.6 nmol/s (22.2, 27.5), n=38, p=0.22. These findings suggest that the thyroid gland and peripheral tissues are integrated in the physiological process of T3 homeostasis in humans via a feed-forward TSH motif, which coordinates peripheral and central regulatory mechanisms. Regulatory and capacity deficiencies collectively impair T3 homeostasis in L-T4-treated patients.