Inhibition of conversion of thyroxine to triiodothyronine in patients with severe chronic illness.

Many clinically euthyroid patients with severe, chronic, non-throidal illnesses (i.e. sick euthyroid patients) have very low circulating concentrations of total and absolute free triiodothyronine (T3), low-normal concentrations of total thyroxine (T4), elevated concentrations of absolute free T4, and circulating concentrations of thyrotrophin (TSH) that are either normal or subnormal. This study was undertaken to elucidate the mechanism of the low circulating T3 concentrations. The disappearance rate of 125 I-T3 from the circulation of five representative sick euthyroid patients was studied and found to be slower, but not significantly so, compared with three control subjects, thus excluding an increased destruction rate as the cause of the low T3 levels. A selective decrease of T3 secretion from the thyroid gland of these patients was also excluded by the results of TSH stimulation tests. Inhibition of extra-thyroidal conversion of T4 to T3 was suggested by studies of the thyroid function in a hypothyroid woman with a Grade IV lymphoma on T4 replacement therapy. When the lymphoma was in remission, her circulating T3 concentration was 2-55 nmol/l but when it relapsed it fell to 0-55 nmol/l. The T4 concentrations were 124-7 nmol/l and 126 nmol/1 respectively. Decreased monodeiodination of T4 to T3 in sick euthyroid patients was confirmed by paper chromatography of extracted serum obtained 48 h after an i.v. injection of 125 I-T4 into two severely ill patients from the intensive therapy unit and a control subject. Peaks of radioactivity corresponding to 125 I-T4 and 125 I-T3 were detected in the control subject, but only a single peak corresponding to 125 I-T4 was detected in the ill patients.