Transport of thyroxine into cultured hepatocytes: effects of mild non-thyroidal illness and calorie restriction in obese subjects

Summary OBJECTIVE Inhibitors of cellular T4 transport leading to diminished plasma T3 production have been identified as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) and indoxyl sulphate in uraemia and bilirubin and non‐esterified fatty acids (NEFA) in critically ill patients with hyperbilirubinaemia. We question whether other factors are responsible for the altered thyroid hormone parameters observed in mild illness and during calorie restriction. PATIENTS We studied (I) 18 non‐uraemic patients with non‐thyroidal illness (NTI) (T4 5±60, T3 ±1 1 and rT3 ±0 45 nmoI/I) with serum molar ratios of bilirubin:albumin ±0 17 and NEFA:albumin ±2 6. These molar 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 unidirectional T4 transport into human liver in vivo. MEASUREMENTS We measured iodide production from 125 I‐T4 by incubating rat hepatocytes with 10% human serum. The deiodination of T4 was used as an index of cellular transport of T4 in vivo. RESULTS The mean iodide production from 125 I‐T4 by rat hepatocytes in the presence of 10% serum from NTI patients (98±17%, mean±SD) was not significantly different from the normals (100 ±9%). Calorie restriction in euthyroid obese subjects resulted in a small but significant reduction (‐12%) of iodide production. Calorie restriction increased the total serum NEFA by 91 %. CONCLUSIONS Our study demonstrates that CMPF, indoxyl sulphate, bilirubin and NEFA are not responsible for the inhibition of T4 tissue uptake in patients with mild illness. In addition, studies with calorie restricted obese subjects indicate that high concentration of NEFA during calorie restriction inhibits T4 tissue uptake. This inhibition may partly explain the lower plasma T3 during calorie restriction.