In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is 
decreased, resulting in a decreased serum T3 concentration. We investigated 
whether factors in serum of NTI patients may play a role in this energy-saving 
adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary 
culture was measured in the presence of 10% serum of normal subjects or of 
patients with NTI and related to the severity of disease. Patients with NTI were 
grouped according to serum thyroid hormone abnormalities: group I, serum rT3, 
T3, and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, 
rT3 elevated, T3 and T4 decreased. Compared with metabolism in the presence of 
normal serum, metabolism of T4 and to a lesser extent of T3 was progressively 
decreased in the presence of serum of patients of groups I-IV. A decreased net 
deiodination of T4 and T3 (corrected for differences in free hormone 
concentration) without an increase in conjugated T4 and T3 (corrected for 
differences in free hormone concentration) was observed, similar to results in 
experiments with compounds inhibiting transport into the cells and not the 
metabolic processes (5' deiodination) per se. Deiodination of T4 in vitro was 
correlated with serum T3 concentration of the patient (r = 0.69). Serum of 
patients with NTI influences thyroid hormone handling by hepatocytes comparable 
to the effect of transport inhibitors and not to that of the 5'-deiodinase 
inhibitor propylthiouracil, suggesting that decreased thyroid hormone transport 
over the cell membrane may play a role in lowered T3 production in NTI.