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Thyrotropin Suppression by 3,5-Dimethyl-3'-Isopropyl-LThyronine in Man^*

Endocrinology Section, Medical and Research Services, Veterans Administration Wadsworth Hospital Center, Department of Medicine, University of California, Los Angeles, 90073; and the School of Pharmacy, University of California San Francisco, California 94143

Address requests for reprints to: Dr. J. M. Hershman, Section of Endocrinology, Veterans Administration, Wadsworth Hospital Center, Wilshire and Sawtelle Boulevards, Los Angeles, California 90073.

The thyromimetic activity of 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a nonhalogenated thyroid analog, was studied in adult men using suppression of TRH-induced TSH release to assess this activity. In nine men, aged 30-58 yr, the TSH increment after 500 jug TRH iv was compared to the TSH response to TRH 24 h after oral administration of 1 mg DIMIT. Eight euthyroid subjects had normal baseline TSH levels of 1.5 ± 0.2 (SE) µU/ml that fell significantly to 0.7 ± 0.2 µU/ml 24 h after DIMIT (P < 0.005). Their TSH increments after TRH fell from 15.3 ± 2.8 to 6.7 ± 1.6 µU/ml 24 h after DIMIT (P < 0.001). One subject with probable Hashimoto's thyroiditis had an elevated TSH of 18 µU/ml, with an exaggerated TSH response to TRH of 72 µU/ml. His basal TSH fell to 7.6 and his TSH increment fell to 14.3 µ/ml 24 h after DIMIT. The suppression of TSH was relatively prolonged. In four subjects, the TSH response to TRH was still blunted from 5-12 days after DIMIT. In one subject, the TSH increment returned to normal 15 days after DIMIT. DIMIT had no significant effect on PRL secretion. There was no evidence of toxicity in patients receiving DIMIT. DIMIT has effective thyromimetic activity in man, as shown by its significant and prolonged suppression of TSH secretion. (J Clin Endocrinol Metab 48: 196, 1979)

^* This work was supported by the V.A. Medical Research Service and USPHS Grants HD-7181 and AM-17576.

Received August 28, 1978.