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 2.5μM 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≥80ng/dl), Group II (80<T₃≥50) and Group III (50<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±11ng/dl) and TSH (1.2±1.1μU/ml) were significantly lower than that of survivors in Group III (T₃; 38±10ng/dl p<0.005, TSH; 2.8±1.4μU/ml p<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± SDng/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. The incidences of positive IEC were 60.9, 47.6, 16.7 and 16.7% respectively. Three patients of eight nonsurvivors suffered from respiratory failure and their IEC were all negative. But all other five patients died of nonrespiratory diseases showed positive IEC.
In nine patients with diabetes mellitus followed, serum T₃ (ng/dl) concentration increased significantly from 69±27 to 88±35 after insulin therapy, and their %T₃ productions also increased from 67.0±18.4 to 101.3±20.5.
In conclusion, 1) IEC was one of the causative factors in low T₃ state in patients with various NTI, 2) the degree of contribution of IEC to low T₃ state was different among the underlying illnesses and 3) IEC might disappear when clinical course of underlying illnesses improved.