THYROTROPIN SUPPRESSION BY 3,5-DIMETHYL-3'-ISOPROPYL-L-THYRONINE IN MAN

被引:23
作者
TAMAGNA, EI
HERSHMAN, JM
JORGENSEN, EC
机构
[1] VET ADM WADSWORTH HOSP CTR, MED SERV, ENDOCRINOL SECT, LOS ANGELES, CA 90073 USA
[2] VET ADM WADSWORTH HOSP CTR, RES SECT, LOS ANGELES, CA 90073 USA
[3] UNIV CALIF SAN FRANCISCO, SCH PHARM, SAN FRANCISCO, CA 94143 USA
[4] UNIV CALIF, DEPT MED, LOS ANGELES, CA 90073 USA
关键词
D O I
10.1210/jcem-48-2-196
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The thyromimetic activity of 3,5-dimethyl-3́-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 μU/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. © 1979 by The Endocrine Society.
引用
收藏
页码:196 / 200
页数:5
相关论文
共 20 条
[1]   TIME COURSE OF CHANGES IN TRH RESPONSIVENESS IN MAN FOLLOWING A SINGLE DOSE OF LIOTHYRONINE [J].
AZIZI, F ;
VAGENAKIS, AG ;
INGBAR, SH ;
BRAVERMAN, LE .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1975, 24 (06) :691-694
[2]   PLASMA THYROTROPIN, THYROXINE, AND TRIIODOTHYRONINE RELATIONSHIPS IN MAN [J].
AZUKIZAWA, M ;
PEKARY, AE ;
HERSHMAN, JM ;
PARKER, DC .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1976, 43 (03) :533-542
[3]  
BALLARD PL, 1978, PEDIATR RES, V12, P1164
[4]   DIFFERENTIAL EFFECTS OF TRIIODOTHYRONINE AND 3,5-DIMETHYL-3'-ISOPROPYL-L-THYRONINE TREATMENT OF MATERNAL RATS UPON HEPATIC L-TRIIODOTHYRONINE AMINOTRANSFERASE ACTIVITY IN FETAL RATS [J].
BENSON, MC ;
LIU, JP ;
HUANG, YP ;
BURGER, A ;
RIVLIN, RS .
ENDOCRINOLOGY, 1978, 102 (02) :562-567
[5]   THYROID-HORMONE ANALOGS AND FETAL GOITER [J].
COMITE, F ;
BURROW, GN ;
JORGENSEN, EC .
ENDOCRINOLOGY, 1978, 102 (06) :1670-1674
[6]   THYROMIMETIC ACTIVITY OF METHYLTHYRONINES IN BULLFROG TADPOLE [J].
FRIEDEN, E ;
YOSHIZATO, K .
ENDOCRINOLOGY, 1974, 95 (01) :188-194
[7]  
JORGENSEN EC, 1974, J MED CHEM, V17, P434, DOI 10.1021/jm00250a014
[8]   STRUCTURE ACTIVITY RELATIONSHIPS OF THYROXINE ANALOGS [J].
JORGENSEN, EC .
PHARMACOLOGY & THERAPEUTICS PART B-GENERAL & SYSTEMATIC PHARMACOLOGY, 1976, 2 (04) :661-682
[9]  
KOERNER D, 1975, J BIOL CHEM, V250, P6417
[10]   EFFECTS OF A THYROID-HORMONE ANALOG ON FETAL RAT HEPATOCYTE ULTRASTRUCTURE AND MICROSOMAL FUNCTION [J].
KRIZ, BM ;
JONES, AL ;
JORGENSEN, EC .
ENDOCRINOLOGY, 1978, 102 (03) :712-722