TRANSPORT OF THYROXINE INTO CULTURED-HEPATOCYTES - EFFECTS OF MILD NONTHYROIDAL ILLNESS AND CALORIE RESTRICTION IN OBESE SUBJECTS

OBJECTIVE Inhibitors of cellular T4 transport leading to diminished pl asma T3 production have been identified as 3-carboxy-4-methyl-5-propyl -2-furanpropanoic acid (CMPF) and indoxyl sulphate in uraemia and bili rubin and nonesterified fatty acids (NEFA) in critically ill patients with hyperbilirubinaemia. We question whether other factors are respon sible for the altered thyroid hormone parameters observed in mild illn ess and during calorie restriction. PATIENTS We studied (i) 18 non-ura emic patients with non-thyroidal illness (NTI) (T4 greater than or equ al to 60, T3 less than or equal to 1.1 and rT3 greater than or equal t o 0.45 nmol/l) with serum molar ratios of bilirubin:albumin less than or equal to 0.17 and NEFA:albumin less than or equal to 2.6. These mol ar ratios have been shown to be the minimum ratios which inhibited T4 transport into rat hepatocytes; (ii) four obese euthyroid subjects on 600 kcal/day for 10-14 days. This diet is known to inhibit the unidire ctional T4 transport into human liver in vivo. MEASUREMENTS We measure d iodide production from I-125-T4 by incubating rat hepatocytes with 1 0% human serum. The deiodination of T4 was used as an index of cellula r transport of T4 in vivo. RESULTS The mean iodide production from I-1 25-T4 by rat hepatocytes in the presence of 10% serum from NTI patient s (98 +/- 17%, mean +/- SD) was not significantly different from the n ormals (100 +/- 9%). Calorie restriction in euthyroid obese subjects r esulted in a small but significant reduction (-12%) of iodide producti on. Calorie restriction increased the total serum NEFA by 91%. CONCLUS IONS Our study demonstrates that CMPF, indoxyl sulphate, bilirubin and NEFA are not responsible for the inhibition of T4 tissue uptake in pa tients with mild illness. In addition, studies with calorie restricted obese subjects indicate that high concentration of NEFA during calori e restriction inhibits T4 tissue uptake. This inhibition may partly ex plain the lower plasma T3 during calorie restriction.