STUDY OF SERUM 3,5,3'-TRIIODOTHYRONINE SULFATE CONCENTRATION IN PATIENTS WITH SYSTEMIC NONTHYROIDAL ILLNESS

Sulfation is an important pathway of triiodothyronine (T-3) metabolism . Increased serum T-3 sulfate (T3S) values have been observed during f etal life and in pathological conditions such as hyperthyroidism and s elenium deficiency. Similar variations have also been reported in a sm all number of patients with systemic non-thyroidal illness, but the un derlying mechanisms have not been elucidated. In this study, serum T3S concentrations have been measured by a specific radioimmunoassay in 2 8 patients with end-stage neoplastic disease (ESND) and in 44 patients with chronic renal failure (CRF); 41 normal subjects served as contro ls. Both ESND and CRF patients had lower serum total T-4 (TT4) and tot al T-3 (TT3) than normal controls, while serum reverse T-3 (rT(3)) was increased significantly in ESND (0.7 +/- 0.5 nmol/l: p < 0.001 vs. co ntrols) but not in CRF (0.3 +/- 0.1 nmol/l). The TT3/rT(3) ratio, an i ndex of type I iodothyronine monodeiodinase (type I MD) activity, was reduced significantly in both groups of patients, Serum T-4-binding gl obulin (TBG) was decreased in CRF but not in ESND patients. Serum T3S was significantly higher both in ESND (71 +/- 32 pmol/l) and CRF (100 +/- 24 pmol/l) than in controls (50 +/- 16 pmol/l, p < 0.001). Serum T 3S values showed a positive correlation with rT(3) values and a negati ve correlation with both TT3 and FT3 values in ESND, but not in CRF. I n the latter group a positive correlation was observed between T3S and TBG values. The T3S/FT3 ratio was higher both in CRF (18 +/- 5) and i n ESND (23 +/- 18) as compared to controls (10 +/- 4). Serum inorganic sulfate was increased and correlated positively with T3S values in CR F patients. In conclusion, the results of this study in a large series of patients confirm that patients with systemic non-thyroidal illness have increased serum T3S levels. The mechanisms responsible for these changes appear to be different in ESND and CRF patients. In ESND the increase in serum T3S levels is mainly related to reduced degradation of the hormone by type I MD, whereas in CRF it might be driven by the enhanced sulfate ion concentration, and could be partially dependent o n the impaired renal excretion of T3S. Because T3S can be reconverted to T-3, it is possible that increased T3S concentrations contribute to maintenance of the euthyroid state in systemic non-thyroidal disease.