Summary
The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ath) vs those with pituitary-dependent hyperadrenocorticism (pdh). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocortical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ath (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with pdh. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment.
Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (± sd) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 ± 9.4 for dogs with ath vs 45.7 ± 11.9 for dogs with pdh. The mean plasma cortisol concentrations 1 hour after acth administration at the 7-day recheck were significantly higher in dogs with ath (502 ± 386 nmol/L) than in dogs with pdh (88 ± 94 nmol/L). At 30 days, the mean daily dose of mitotane and post-acth cortisol concentration were significantly greater in dogs with ath (28.8 ± 15.4 mg/kg/d; 392 ± 356 nmol/L, respectively) than in dogs with pdh (10.5 ± 7.5 mg/kg/d; 99 ± 72 nmol/L, respectively). After 90 days of treatment, these values were larger (25.3 ± 16.8 mg/kg/d; 340 ±193 nmol/L in dogs with ath vs those in dogs with pdh (5.4 ± 2.5 mg/kg/d, 110 ± 94 nmol/L) and again after 180 days (26.0 ± 22.1 mg/kg/d, 268 ± 152 nmol/L in dogs with ath vs 6.3 ± 3.4 mg/kg/d, 80 ± 116 nmol/L in dogs with pdh). Clinical signs were consistent with laboratory values, that is, cortisol control was not as good in dogs with ath as in the dogs with pdh. On the basis of these findings, we suggest that dogs with hyperadrenocorticism caused by ath are more resistant to mitotane than are dogs with pdh.
