Organ-specific effects of tiratricol: a thyroid hormone analog with hepatic, not pituitary, superagonist effects.
Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. A randomized, double-blind trial was performed to define precisely the tissue-specific thyromimetic actions of tiratricol. Ten athyreotic patients, treated for thyroid carcinoma, were randomly assigned to receive L-T4 sodium 0.7 micrograms/kg daily and either tiratricol 10 micrograms/kg or placebo twice daily. The daily dose of L-T4 was increased by 25-50 micrograms increments until the TRH-stimulated TSH level was less than 0.1 mU/L. After measurement of biochemical and physiological parameters of thyroid hormone actions, patients crossed treatment groups. Patients required 46% less L-T4 to achieve equivalent TSH suppression when taking tiratricol. Hepatic effects were enhanced by tiratricol administration, with significant increases in sex hormone binding globulin and ferritin concentrations, 14% and 37%, respectively. Levels of serum cholesterol, LDL cholesterol, and apolipoprotein B were reduced by 7%, 10%, and 13%, respectively, during tiratricol therapy. Triglyceride levels also declined, but there were no changes of high density lipoprotein cholesterol or apolipoproteins AI and AII. Resting metabolic rate, body weight, urea nitrogen excretion, and symptoms did not differ between the two treatment regimens. Cardiovascular function, as reflected by mean arterial pressure and pulse wave arrival time, was not different during tiratricol therapy. Skeletal metabolic activity was affected by tiratricol, with marked elevation of osteocalcin without significant change in serum calcium, PTH, and urinary calcium and hydroxyproline excretion. Tiratricol has increased hepatic and skeletal actions of potential therapeutic value, but does not have enhanced thyromimetic activity specific to the pituitary gland.
Sherman
S I
SI
Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-4904.
Ladenson
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PW
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008660:Metabolism / Q000187:drug effects; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects*; D011182:Postoperative Care; D013961:Thyroid Gland / Q000187:drug effects / Q000503:physiopathology; D013963:Thyroid Hormones / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000601:surgery; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D013963:Thyroid Hormones; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid