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

Abstract

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 microgram 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) microunit/ml that fell significantly to 0.7 +/- 0.2 microunit/ml 24 h after DIMIT (P less than 0.005). Their TSH increments after TRH fell from 15.3 +/- 2.8 to 6.7 +/- 1.6 microunit/ml 24 h after DIMIT (P less than 0.001). One subject with probable Hashimoto's thyroditis had an elevated TSH of 18 microunit/ml, with an exaggerated TSH response to TRH of 72 microunit/ml. His basal TSH fell to 7.6 and his TSH increment fell to 14.3 microunit/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.

Transplacental stimulation of lung development in the fetal rabbit by 3,5-dimethyl-3'-isopropyl-L-thyronine.

“…At the one dose investigated, clearance of DIMIT from plasma ofthe rat appears to be slower than reported for T3 (43). A relatively slow clearance of DIMIT apparently also occurs in adult humans (44). The combination of higher concentrations and slower clearance of DIMIT from the fetal circulation of the rat would favor preferential effects of DIMIT in the fetus.…”

Thyroid Function Testing

“…Thyroid hormones (T4 and T3) Replacement therapy, antigoitrogenic, and anticancer Thyroid hormone analogues (DT4, 471 3′,3′,5-TRIAC, 472 etiroxate-HCI, 473 dimethyl-3 isopropyl-L-thyronine 474 Treatment for cerebrovascular diseases and migraine Dopamine antagonist (pimozide) 254 Neuroleptic α-Noradrenergic blockers 479,480 (phentolamine, thioridazine) Neuroleptic Serotonin antagonists (metergoline, 481 cyproheptadine, 482 methysergide 483 ) Antimigraine and appetite stimulators Serotonin agonist (5-hydroxytryptophan) 463 -Glucocorticoids 484,485 Antiinflammatory, antiimmunosuppressive, and anticancer; reduction of intracranial pressure Acetylsalicylic acid 164 Antiinflammatory, antipyretic, and analgesic Growth hormone 165 * Growth promoting Somatostatin 166 Antineoplastic Octreotide 486 Opiates (morphine, 487 leuenkephalin, 488 heroin 409 ) Analgesic Clofibrate 489 Hypolipidemic Fenclofenac 403,432 Nonsteroidal antiinflammatory drug Bexarotene 490 T cell lymphoma IL-6 443 Biotin 194,195 Immune modulating Interference with biotin-strepavidin complexes DT4, Dextrothyroxine; IL, interleukin; T3, triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone; TRIAC, triiodothyroacetic acid;…”

Transplacental effects of 3,5-dimethyl-3'-isopropyl-L-thyronine on tubulin content in fetal brains in rats.

“…3, 5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT) has demonstrable thyromimetic activity in many primates (BACHRACH et al, 1983;MELMED et al, 1980;TAMAGNA et al, 1979), and is capable of transplacental movement (COMITE et al, 1978). BACHRACH et al (1983) have recently demonstrated that the administration of DIMIT to 131I-treated mothers prevents the clinical manifestations of cretinism in the fetus using monkeys.…”