An inhibitor of extrathyroidal conversion of thyroxine to 3,5,3'-triiodothyronine (IEC) in plasma of patients with various nonthyroidal illnesses

Abstract

To evaluate the role of a circulating inhibitor of extrathyroidal conversion of T4 to T3 (IEC) in the causation of low T3 states in patients with various nonthyroidal illnesses (NTI), we measured the in vitro T3 production in the presence of ether extract of plasma. Blood samples were obtained from 22 normal subjects and 140 patients with various NTI; liver cirrhosis (LC) 37, diabetes mellitus (DM) 48, respiratory failure (RF) 15, chronic renal failure (CRF) 10 and others 30. The assay procedure of in vitro T3 production was as follows. Rat liver homogenate was incubated with 2.5 microM T4 in the presence of evaporated ether extract of plasma and the amount of T3 produced was quantified by RIA. In each assay, control plasma extracts taken from the two normal subjects were used. The results were expressed as a percentage of the control value (%T3 production), and estimated as positive IEC when %T3 production was under 72.7%, that was 2SD below the mean value of normal controls. Patients were divided into three groups; Group I (T3 greater than or equal to 80 ng/dl), Group II (80 greater than T3 greater than or equal to 50) and Group III (50 greater than T3). The %T3 productions were 88.5 +/- 22.0 in Group I, 84.9 +/- 31.5 in Group II and 78.9 +/- 34.0 in Group III respectively. The %T3 productions of each group were significantly lower than that of normal control, 101.9 +/- 14.6. IEC was positive 23.4% in Group I, 41.9% in Group II and 43.8% in Group III. There were eight nonsurvivors, and they all belonged to Group III, in which both serum T3 and T4 were subnormal. In nonsurvivors, serum concentrations of T3 (20 +/- 11 ng/dl) and TSH (1.2 +/- 1.1 microU/ml) were significantly lower than that of survivors in Group III (T3; 38 +/- 10 ng/dl p less than 0.005, TSH; 2.8 +/- 1.4 microU/ml p less than 0.05). The %T3 productions were 83.8 +/- 32.1 in survivors and 64.8 +/- 37.9 in nonsurvivors, and the incidences of positive IEC were 37.5% in survivors and 62.5% in nonsurvivors. From the standpoint of the underlying illnesses, serum concentrations of T3 (mean +/- SD ng/dl) were 49 +/- 21 in LC, 64 +/- 11 in DM, 40 +/- 22 in RF and 63 +/- 15 in CRF, and %T3 productions were 60.6 +/- 26.5 in LC, 82.5 +/- 25.8 in DM, 109.6 +/- 32.1 in RF and 97.6 +/- 24.3 in CRF.(ABSTRACT TRUNCATED AT 400 WORDS)