Inhibition of Conversion of Thyroxine to Triiodothyronine in Patients With Severe Chronic Illness

Abstract

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.

Peripheral Serum Thyroxine, Triiodothyronine and Reverse Triiodothyronine Kinetics in the Low Thyroxine State of Acute Nonthyroidal Illnesses

“…The T3 PR was markedly reduced in our patients, which is a feature common to other nonthyroidal illnesses (6)(7)(8). T3 production could be reduced as a result of decreased free T4 availability or to impaired enzymatic deiodination of T4.…”

“…roxine (TT4)' in association with normal serum thyrotropin (TSH) levels (1)(2)(3)(4)(5). In addition, total serum triiodothyronine (TT3) levels are decreased, and total reverse T3 (TrT3) values are usually increased (1, [3][4][5], as in other nonthyroidal illnesses (6)(7)(8)(9).…”

Total and free thyroid hormone concentrations after elective surgery.

“…These data confirm the findings of other authors with respect to the total hormone concentrations. Recent work (Carter et al, 1976) suggests that the peripheral conversion of T4 to T3 is diminished and that increased amounts of the alternative metabolite (rT3) are formed preferentially. There is growing evidence that more than one enzyme is involved and that there are specific deiodinases for inner and outer ring deiodination.…”

Peripheral Metabolism of Hormones: Clinical Implications

“…Of interest has been the growing list of conditions in which T3 production has been shown to be impaired, usually linked to a rise in serum rT3, due either to increased synthesis or decreased clearance. This list includes acute stress (Burr et al 1975), acute (Burger et al 1976)and chronic illness (Carter et al 1976), starvation (Vagenakis et al 1975), liver disease (Nomura et al 1975) and administration of propylthiouracil (Oppenheimer et al 1972),glucocorticoids (Chopra et al 1973), propranolol (Lotti et al 1977). Similar changes reported in the elderly probably reflect associated illness rather than the ageing process per se.…”