Opposite Effects of Dexamethasone on Serum Concentrations of 3, 3′,5′-Triiodothyronine (Reverse T₃) and 3,3′,5′-Triiodothyronine (T₃)

Abstract

Dexamethasone, 2 mg every 6 hours for 4 doses, was given to 4 hypothyroid patients receiving treatment with synthetic thyroxine (T4) and to 8 untreated hyperthyroid patients with Graves' disease, and serum concentrations of thyroid hormones were measured by radioimmunoassays. Serum concentration of 3,3'5'-triiodothyronine (reverse T3, rT3) increased appreciably within 8 hours after the first dose of dexamethasone, was maximum at 24-32 hours after beginning dexamethasone, and remained elevated for about 24 hours after discontinuing the steroid. The mean baseline serum rT3 was 58 ng/per 100 ml in treated hypothyroid patients and 119 ng per 100 ml in patients with Graves' disease; the corresponding maximal post-dexamethasone serum rT3 values were 87 and 170 serum concentration of 3,3',5-triiodothyronine (T3) decreased. The decrease in serum T3 was significant at about 24 hours after beginning dexamethasone and was maximal at about 30 hours in both groups of cases under study. The decrease in serum T3 persisted in treated hypothyroid cases for about 24-48 hours and in Graves' disease cases as long as studied, at least 5 days after discontinuing hexamethasone. The changes in serum rT3 and T3 could not be attributed to the effect of dexamethasone on serum protein binding of the iodothyronines because the dialyzable fractions of rT3 and T3 following steroid administration were not different from those before it. Serum T4 did not change appreciably in treated hypothyroid cases, but decreased in Graves' disease cases from a mean baseline value of 23.5 mug per 100 ml to 18.4 mug per 100 ml 3 days after beginning dexamethasone. In addition, 3 hyperthyroid cases were studied before, during, and after administration of dexamethasone, 2 mg every 6 h for 5 days. Serum rT3 increased again as noted above and the increase persisted until about 24 hours after the last dose of the steroid. Serum T3 decreased considerably and remained decreased as long as studied, at least 4 days after discontinuing the steroid. Serum T4 decreased appreciably in 2 of the 3 cases studied. The data suggest that 1) conversion of T4 to T3 and to rT3 may occur via two distinct pathways in the metabolism of T4; 2) the changes in serum rT3 and T3 observed in our study may be due in part at least to a steroid-induced 'shift' in the metabolism of T4 whereby conversion of T4 to T3 is diminished and that to rT3 is enhanced; 3) in addition to the effect on peripheral metabolism of T4, steroids appear to reduce the circulating thyroid hormones in Graves' disease by another mechanism, probably by reduction in thyroid secretion.

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

“…Similar situation has also been observed in normal fetus in whom serum T3 is less than, and serum rT3 is much higher than the adult levels (8). These observations suggest the possibility that alterations in monodeiodination of T4 observed in hepatic cirrhosis and the fetus may also be the explanation in other situations where serum T3 is low and rTs is high (9,36,38).…”

“…The Journal of Clinical Investigation Volume 58 July 1976- [32][33][34][35][36][37][38][39][40] turnover rate of reverse T3. Similarly, little information is available regarding the relative significance of the contribution of the thyroidal secretion and the peripheral metabolism of T4 to serum rTa in man.…”

Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

“…Short-term high-dose dexamethasone administration in man decreases serum T 3 and increases rT 3 concentrations, an effect attributed to the inhibition of type I deiodinase in the liver (37). Whether hypercortisolism in the human (or experimental animal) can affect the other types of tissue-specific deiodinase has not been studied in detail.…”

Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation

“…This reflects the fact that patients who required steroids were sicker than those not receiving steroids and that steroids inhibit T4 to T3 conversion and reduce TBG concentration. 34,35 Glucocorticoids are known to inhibit TSH secretion in a dose-dependent manner. 36,37 Surprisingly, in our patients TSH did not differ between the two groups either receiving corticosteroids or not.…”