Effect of thyroid hormone supplementation on chronic doxorubicin (adriamycin)-induced cardiotoxicity and serum concentrations of T3 and T4 in dogs.

Chronic doxorubicin (adriamycin; ADR) intoxication was produced in Beagle dogs by weekly IV injections (1 mg/kg of body weight) for 20 weeks (cumulative dose 400 mg of ADR/m2). Group A (5 dogs) were given ADR only; group B (5 dogs), ADR and daily supplements of 0.5 mg of L-thyroxine (T4) (twice the recommended maintenance dose); and group C (5 dogs), ADR and 2.0 mg of T4 daily (8 times the recommended maintenance dose). The control group D (5 dogs) was given 0.5 mg of T4 daily. The ADR-induced cutaneous lesions (alopecia and melanosis), body weight loss, hematologic alterations, and myocardial microscopic and ultrastructural alterations (sarcoplasmic vacuolation and myocytolysis) were present with equal severity in the 3 ADR-treated groups, with or without T4 supplements. Six of the 15 ADR-treated dogs died during the study: 3 dogs had pneumonia, 1 dog had no established cause of death, and 2 dogs (from group C) had lesions of congestive cardiac failure. All ADR-treated dogs given a cumulative dose of 340 mg of ADR/m2 or more had characteristic myocardial histopathologic alterations, but 2 dogs that died after they were given only 140 or 260 mg of ADR/m2 had no microscopic evidence of myocardial damage. Low serum triiodothyronine (T3) concentrations were present in ADR-treated dogs after 28, 56, 84, 112, and 140 days and were attributed to faulty extrathyroidal conversion of T4 to T3. Serum T4 concentrations were high in dogs given 2 mg of T4/day (group C) after 28, 56, 84, and 112 days, but were low terminally as those dogs became debilitated from chronic ADR toxicosis. Unusual clinical signs or cardiac alterations of hyperthyroidism did not develop in the dogs given T4 supplements (groups B, C, and D). Our findings indicate that supplements of T4 do not alter the development of the cardiac and extracardiac lesions of chronic ADR toxicosis in dogs and indicate that the ADR-induced lesions probably are not mediated via hypothyroidism.