Dissociated thyromimetic effects of 3, 5, 3′-triiodothyroacetic acid (TRIAC) at the pituitary and peripheral tissue levels1

Although TRIAC is bound at least twice as avidly to nuclear receptor as T3, its thyromimetic potency is relatively low and its effect at the pituitary level on thyrotropin (TSH) secretion seems to be dissociated from that at the peripheral tissue level. In order to gain further insight into the complex effects of this thyroid hormone analog, we studied the effects of long-term TRIAC administration (2.8 mg/day for 2 months) on TSH secretion, circulating free thyroid hormone (FT4 and FT3) levels and some parameters able to evaluate the peripheral thyroid hormone action, in 5 mild obese subjects on low caloric diet (1200 kcal /day). The results were compared to those obtained in 5 mild obese subjects matched for age, sex and weight on low caloric diet alone. TRIAC administration completely inhibited the secretion of both basal and TRH-stimulated TSH in few days, and consequently serum FT4 and FT3 concentrations progressively dropped to very low levels, while no significant changes in both TSH and free thyroid hormone levels were recorded in the control group. The body weight significahtly fell in both groups, without any difference between TRIAC treated and untreated patients. The heart rate was constant throughout the course of the study in both groups of patients. Serum total cholesterol, triglyceride and total lipid concentrations significantly decreased in both groups, and the decrement recorded in TRIAC treated patients was not significantly different from that found in patients on diet alone. The low serum levels of sex hormone-binding globulin (SHBG) completely normalized in both groups (TRIAC + diet: from 19.9 ± 7.4 to 49.0 ± 14.5 nmol /l, p <0.01; diet alone: from 29.0 ± 6.0 to 50.6 ± 5.2 nmol/l, p <0.01), without any difference between TRIAC treated and untreated patients. The present data confirm the previously reported discrepancy between the strong in vitro nuclear binding of TRIAC and its poor thyromimetic activity in vivo, and demonstrate that TRIAC at the dose which completely suppresses TSH secretion does not cause any particular metabolic effect at the peripheral tissue level.