J Endocrinol. Invest. 4. 343, 1981 Relative ineffectiveness of exogenous triiodothyronine as a thyroid suppressive agent1 D.A. Koutras, J. Malamitsi, A. Souvatzoglou, G.D. Piperingos, D.P. Livadas, M. Boukis, D.N. Papachristou, J. Sfontouris, and S.D. Moulopoulos Athens University, Department of Clinical Therapeutics, Alexandra Hospital, Athens 611, Greece ABSTRACT. In 16 patients with nontoxic goiterT 3 was given orally, 20l1g daily forthefirst month, 40l1g for the second and 60 I1g for the third. Before and at the end of each month the basal serum TSH levels and the 30 min response to 200 I1g TRH iv were measured. The difference was calculated as TSH. Serum T 4, T 3 resin uptake, and T 3were measured at the beginning and at the end of treatment. The results were compared to those obtained in 2 groups of 18 and 54 patients, respectively, treated with increasing doses of oral T4. In the patients treated with exogenous T3 there was a rise of serum T3 from 2.02 ± 0.06 to 3.48 ± 0.08 nmol/I, and while on 60 I1g/day all had serum T 3levels well within the hyperthyroid range. However, the TRH test became negative in only 62.5% of them. On the contrary, in the groups treated with T.j the TRH test was promptly sup- pressed completely, and TSH became 0 with 100 I1g of 1\ daily in virtually all cases. It is concluded that although 60 I1g of T3 are more than the daily maintainance dose and result in hyperthyroid serum T3 levels, the pituitary-thyroid axis is not completely suppressed, probably because pituitary TSH secretion is regulated by the intrapituitary conversion ofT 4 to T 3 and not by serum T3 levels. Hence, if one wants to suppress the pituitary TSH release, as in the treatment of nontoxic gOiter, T4 and not T3 is the drug of choice: it is selectively converted to T3 in the pituitary, where it produces higherT 3levels and so more complete suppression of the TSH release, without unduly high serum T3 levels and thyrotoxiC manifestations from the peripheral tissues. INTRODUCTION Both thyroxine (T4) and triiodothyronine (T3) are used as substitutions in hypothyr'oidism or as suppressive treatment in nontoxic goiter and thyroid cancer, either singly or in combination, Thyroxine is usually preferred because of its gradual conversion to T3 and its longer action, but T3 is also frequently advocated and quite extensively used, Several clinical studies in hypothy- roid patients have shown T 3 to be about 4 times more potent than T4 (1-7). This is now well accepted in clinical practice, and stated in most textbooks on the thyroid, It is in good agreement with the conclusion that T 3 is experimentally 5.5 times more active than T4 on a molar basi,s (8), The occasional finding of a measurable TRH response in patients taking full doses of exogenous T 3 has led to this study, which compares the effect of T 3 on the TRH test to that previously reported by us for T4 (9), The 1 Supported by a Research Contract from the Hellenic Ministry for Soc,al Services Key-words· Nontoxic goiter treatment. thyroid suppression. thyroxine. TRH test. triiodothyronine. Correspondence· Demetrios A Koutras. Athens University. Department of Clinical Therapuet,cs. Alexandra HospitaL Athens 611, Greece Rece,ved January 4. 1981. accepted April 8. 1981 343 initial hypothesis was that since the administration of exogenous T3 does not result in constant T 3 levels, this would not lead to a consistent suppression of TRH test. The results presented below show that indeed exog- enous T 3 is not a good suppressive agent, though the reason is probably not the one initially postulated, MATERIALS AND METHODS Following informed consent, 16 goitrous patients (Group 1) were studied in the endemic areas of Greece (1 male and 15 females, age from 15 to 70 yr), The goiter size, estimated by palpation (10), ranged be- tween 35 an 70 g, All gOiters were diffuse, Definite nodular gOitres were excluded, because of the auton- omy possibly present (11-13), The results were compared to those obtained in 2 others groups. Group 2 consisted of 18 goitrous pa- tients (18 females age 18 to 40 yr) and Group 3 of 54 goitrous patients (4 males and 50 females, age 18 to 65 yr). The patients of Groups 2 and 3 were also from the endemic areas, but were studied in Athens. Group 3 was previously reported (9). The protocol was in general similar to that previously used by Koutras et aL (9) for thyroxine, but since part of the study was performed in the field, only the TRH test was performed, and not the thyroid uptake suppression