Iodothyronine deiodination in rats with severe non-thyroidal illness

To investigate the iodothyronine metabolism in non-thyroidal illness (NTI), thyroidectomized male Wistar rats bearing the hypercalcemic Walker sarcoma 256 were substituted with, respectively, 2.3 and 11.5 mumol T4/100 g body weight by daily ip injection. Serum T4 and T3 concentrations of euthyroid and hyperthyroid tumor-bearing animals markedly decreased to a nadir at day 8 after tumor implantation: serum T4 fell to, respectively, 43% (euthyroid) and 26% (hyperthyroid) of initial values, serum T3 to 19% (euthyroid) and 26% (hyperthyroid). A measurable serum rT3 concentration could not be detected before and after tumor implantation. In vitro deiodination of T4 to T3 in liver homogenates of the sacrificed animals was not significantly reduced in Walker rats compared with control animals. The activity of T4 deiodinase was significantly induced in hyperthyroid controls (180%) as well as in hyperthyroid Walker rats (155%) in spite of low serum concentrations of T4 and T3. This enzyme induction was even more pronounced in animals whose treatment with high T4 doses was started after tumor implantation. In these rats the serum concentrations of free fatty acids were increased to about 200% of controls. Our data suggest that 1. the fluctuations of iodothyronine serum concentrations in NTI are mainly independent of thyroidal secretion, and 2. the intracellular iodothyronine levels in livers of severely sick animals with different thyroid function are not greatly altered by NTI, in spite of markedly decreased total serum levels.