A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane.

BACKGROUND: Trilostane is a recognized treatment for canine pituitary-dependent hyperadrenocorticism (PDH); however, its efficacy in dogs with adrenal-dependent hyperadrenocorticism (ADH) is unknown. OBJECTIVES: To examine factors that might influence survival in the medical management of ADH, with particular emphasis on treatment selection. ANIMALS: Thirty-seven animals referred to 4 centers over a period of 12 years that had been diagnosed with ADH and treated with either trilostane (22/37), mitotane (13/37), or both (2/37). METHODS: Retrospective analysis of clinical records. RESULTS: There was no statistically significant difference between the survival times of 13 dogs treated only with mitotane when compared with 22 dogs treated only with trilostane. The median survival time for animals treated with trilostane was 353 days (95% confidence interval [CI] 95-528 days), whereas it was 102 days (95% CI 43-277 days) for mitotane. Metastatic disease was detected in 8 of 37 dogs. There was a significantly lower probability of survival for dogs with metastatic disease when compared with those without metastatic disease (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The choice of medical treatment for ADH may not have a major effect on survival times. However, the presence of metastatic disease considerably decreases survival time regardless of the choice of medical treatment.

Monitoring the response of canine hyperadrenocorticism to trilostane treatment by assessment of acute phase protein concentrations.

BACKGROUND: Acute phase proteins (APPS) include haptoglobin (Hp), C-reactive protein (CRP) and serum amyloid A (SAA). Increased Hp concentrations may be induced by endogenous or exogenous glucocorticoids in dogs. OBJECTIVES: To assess whether control of hyperadrenocorticism (HAC) affects the concentrations of Hp, CRP, SAA, alkaline phosphatase (ALKP) and cholesterol, to determine whether these analytes can be used to assess control of HAC following trilostane treatment, and whether a combination of these tests offers a valid method of assessing disease control. METHODS: Hp, CRP, SAA, ALKP and cholesterol were assessed in 11 dogs with spontaneous HAC before and after treatment with trilostane. Adequate control of HAC was defined as post-ACTH cortisol less than 150 nmol/l. RESULTS: Significant reductions in Hp, ALKP, cholesterol and SAA (P<0.05) but not of CRP were found after control of HAC. Only Hp, cholesterol and ALKP were moderately informative (Se & Sp>0.7) of disease control when compared to adrenocorticotropin or corticotropin (ACTH) stimulation test. SAA and CRP were unhelpful (Se & Sp<0.7). The analysis of the combination of the analytes did not improve the correlation with ACTH stimulation test. CLINICAL RELEVANCE: Relying on these analytes does not provide additional information over ACTH stimulation test results when assessing control of HAC treated with trilostane.

Persistent isolated hypocortisolism following brief treatment with trilostane.

A 12-year-old male neutered Miniature Poodle with confirmed pituitary-dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism ('atypical hypoadrenocorticism'), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life-threatening situation.

A comparison of the survival times of dogs treated with mitotane or trilostane for pituitary-dependent hyperadrenocorticism.

The survival times of 148 dogs treated for pituitary-dependent hyperadrenocorticism were studied using clinical records from 3 UK veterinary centers between 1998 and 2003. Of these animals, 123 (83.1%) were treated with trilostane, while 25 (16.9%) were treated with mitotane. Treatment groups were compared using t-tests and analysis of variance (or their nonparametric equivalents) and chi-square tests. Survival data were analyzed using Kaplan-Meier survival plots and Cox proportional hazard methods. There was no significant difference between the population attributes from each center or between treatment groups. The median survival time for animals treated with trilostane was 662 days (range 8-1,971) and for mitotane it was 708 days (range 33-1,399). There were no significant differences between the survival times for animals treated with trilostane and those treated with mitotane. In the multivariable model (including drug, center, breed group, weight, diagnostic group, and age at diagnosis), only age at diagnosis and weight were significantly negatively associated with survival. Importantly, there was no significant effect of drug choice on survival.

Canine hyperadrenocorticism: effects of trilostane on parathyroid hormone, calcium and phosphate concentrations.

OBJECTIVES: To determine the effects of treating canine hyperadrenocorticism (HAC) on parathyroid hormone (PTH), calcium and phosphate concentrations in dogs. METHODS: Serum calcium, phosphate and PTH concentrations were analysed in 22 dogs with HAC before treatment with trilostane and at a median of 210 days after commencing treatment. Pretreatment data were compared with data from an age- and weight-matched group of hospitalised patients, and post-treatment data were compared with pretreatment data. RESULTS: PTH and phosphate concentrations were significantly higher in dogs with HAC compared with control dogs. PTH concentrations reduced significantly with treatment, such that there was no longer a difference between the HAC and control groups. Phosphate concentrations also reduced significantly with treatment but there was still a significant difference between those in dogs with HAC and control dogs. Despite no significant difference between calcium concentrations in the pretreatment HAC and control groups, calcium concentrations increased significantly with treatment. CLINICAL SIGNIFICANCE: These results show that adrenal secondary hyperparathyroidism resolves with treatment and suggest that increased calcium and phosphate levels have a role in its pathogenesis.

Diagnosis and management of B cell chronic lymphocytic leukaemia in a cat.

A four-year-old, female neutered domestic shorthair cat had a history of chronic intermittent vomiting and lymphocytosis. B cell chronic lymphocytic leukaemia was diagnosed by flow cytometry, which revealed abnormally large numbers of mature B lymphocytes in the peripheral blood. The cat was treated conservatively with antiemetic drugs and remained stable without chemotherapy for over a year.