Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism

Edward C. Feldman From the Department of Veterinary Reproduction (Feldman), the Veterinary Medical Teaching Hospital (Bruyette), and the Department of Epidemiology and Preventive Medicine (Farver), University of California, Davis, CA 95616, and the Department of Small Animal Clinics, Purdue University, West Lafayette, IN 47907 (Nelson).

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David S. Bruyette From the Department of Veterinary Reproduction (Feldman), the Veterinary Medical Teaching Hospital (Bruyette), and the Department of Epidemiology and Preventive Medicine (Farver), University of California, Davis, CA 95616, and the Department of Small Animal Clinics, Purdue University, West Lafayette, IN 47907 (Nelson).

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Richard W. Nelson From the Department of Veterinary Reproduction (Feldman), the Veterinary Medical Teaching Hospital (Bruyette), and the Department of Epidemiology and Preventive Medicine (Farver), University of California, Davis, CA 95616, and the Department of Small Animal Clinics, Purdue University, West Lafayette, IN 47907 (Nelson).

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Thomas B. Farver From the Department of Veterinary Reproduction (Feldman), the Veterinary Medical Teaching Hospital (Bruyette), and the Department of Epidemiology and Preventive Medicine (Farver), University of California, Davis, CA 95616, and the Department of Small Animal Clinics, Purdue University, West Lafayette, IN 47907 (Nelson).

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Summary

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (± sd) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 ±1.6 µg/dl), lowest in 15 control dogs (1.3 ± 0.5 µg/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (pdh; 3.4 ± 1.2 µg/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P < 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with pdh; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P < 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 ± 0.2 µg/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later.

Twenty dogs with hyperadrenocorticism (11 with pdh, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with pdh failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P < 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (acth). The healthy control dogs had a mean baseline plasma cortisol concentration of 1.4 ± 0.4 µg/dl and a post-acth cortisol concentration of 10.6 ± 3.1 µg/dl. Before ketoconazole administration, all 11 dogs with pdh had a mean baseline plasma cortisol concentration of 4.4 ± l.9 µg/dl and a post-acth cortisol concentration of 33.6 ± 17.6 µg/dl. The 9 dogs with adrenocortical tumor had a mean baseline plasma cortisol concentration of 4.4 ± 1.3 µg/dl and post-acth cortisol concentration of 28.1 ± 14.1 µg/dl. After 5 days of ketoconazole administration, the post-acth plasma cortisol concentration for dogs with pdh or adrenocortical tumor was 4.0 ± 5.4 µg/dl and 6.0 ± 3.3 µg/dl, respectively. Similar responses were observed after 60, 180, and 360 days of ketoconazole treatment.

Summary

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (± sd) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 ±1.6 µg/dl), lowest in 15 control dogs (1.3 ± 0.5 µg/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (pdh; 3.4 ± 1.2 µg/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P < 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with pdh; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P < 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 ± 0.2 µg/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later.

Twenty dogs with hyperadrenocorticism (11 with pdh, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with pdh failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P < 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (acth). The healthy control dogs had a mean baseline plasma cortisol concentration of 1.4 ± 0.4 µg/dl and a post-acth cortisol concentration of 10.6 ± 3.1 µg/dl. Before ketoconazole administration, all 11 dogs with pdh had a mean baseline plasma cortisol concentration of 4.4 ± l.9 µg/dl and a post-acth cortisol concentration of 33.6 ± 17.6 µg/dl. The 9 dogs with adrenocortical tumor had a mean baseline plasma cortisol concentration of 4.4 ± 1.3 µg/dl and post-acth cortisol concentration of 28.1 ± 14.1 µg/dl. After 5 days of ketoconazole administration, the post-acth plasma cortisol concentration for dogs with pdh or adrenocortical tumor was 4.0 ± 5.4 µg/dl and 6.0 ± 3.3 µg/dl, respectively. Similar responses were observed after 60, 180, and 360 days of ketoconazole treatment.

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