MITOTANE (O,P'-DDD) TREATMENT OF 200 DOGS WITH PITUITARY-DEPENDENT HYPERADRENOCORTICISM

Two hundred dogs with pituitary dependent hyperadrenocorticism (PDH) were treated with mitotane at an initial daily dosage of 21 to 69 mg/kg (mean = 45.2 mg/kg) for 5 to 14 days. During the induction period, 194 of the dogs also were given daily maintenance dosages of a glucocorticoid. Fifty of the dogs exhibited one or more adverse effects during initial induction, including weakness, vomiting, anorexia, diarrhea, and ataxia. After completion of the induction period, repeat ACTH stimulation testing revealed significant decreases in mean serum cortisol concentrations when compared with initial values. Twenty-five dogs, however, still responded to exogenous ACTH with serum cortisol concentrations above normal resting range, necessitating daily treatment for an additional 5 to 55 days. In contrast, 70 of the 200 dogs had low post-ACTH serum cortisol concentrations after the induction period. These subnormal serum cortisol concentrations generally increased spontaneously to within normal resting range 2 to 6 weeks after cessation of mitotane. In 184 dogs, mitotane was continued at an initial mean maintenance dosage of 49 mg/kg administered weekly in two to three divided doses. Of these dogs, 107 had one or more relapses of hyperadrenocorticism during treatment. In the 75 dogs that had one relapse, the median maintenance dosage was increased by approximately 35%, whereas the median maintenance dosage in the 32 dogs having two or more relapses was eventually increased by 225% over the initial dosage. After a mean maintenance treatment time of 2.0 years, the final maintenance dosage required in the 184 dogs ranged from 26.8 to 330 mg/kg/week. Concurrent glucocorticoid and mineralocorticoid deficiency (Addison's disease) developed in 11 dogs after 27 days to 3.5 years (median = 4.6 months) of maintenance mitotane. The mean survival time of the 200 dogs was 2.2 years (range = 10 days to 8.2 years). Of the 34 dogs that died or were euthanatized within the initial 6 months, 18 died because of complications of hyperadrenocorticism. In contrast, dogs usually did not die of complications associated with hyperadrenocorticism after the first few months of treatment, when the signs of disease were in remission. Eleven dogs died or were euthanatized as a result of the compressive effects of an expanding pituitary tumor. The results of this study indicate that mitotane is effective and relatively safe for the treatment of dogs with PDH. Of the dogs treated for longer than 3 months, over 80% were considered to have a good to excellent response to treatment. Adverse effects, although they did occur with some frequency, were generally not life-threatening, were related to the development of low serum cortisol concentrations, and usually resolved when the dosage of glucocorticoid was increased.