Spontaneous hyperadrenocorticism in dogs and cats is most commonly (∼90%) caused by a functional pituitary tumour. As pituitary surgery is still an uncommon practice in veterinary science, these animals are generally managed medically using either mitotane or trilostane.
The traditional method of managing PDH in dogs has been long term mitotane (o, pDDD) administration. The essence of this regime is to destroy most of the hyperplastic adrenal cortex with a remission inducing dose of mitotane followed by less frequent but regular dosing to maintain remission. The aim of this chemical adrenalectomy is to reduce the level of functioning adrenocortical tissue to a level that provides no more than normal cortisol production despite being subjected to supraphysiological levels of ACTH.
Trilostane a competitive inhibitor of 3β hydroxysteroid dehydrogenase is an alternative to mitotane. Trilostane has been shown to be effective in resolving the clinical signs of PDH in most dogs and in most cases these changes parallel marked reductions in post-ACTH cortisol concentrations within 10 days of treatment although in some dogs these goals were only obtained by marked increases in the daily dose.
Although trilostane seems to be well tolerated by most dogs, early case series reported the development of irreversible hypoadrenocorticism in upto 15% of PDH dogs receiving the drug. Since trilostanes inhibition of steroid synthesis is less than 20 hours the development of clinically significant hypoadrenocorticism suggests other factors must be involved.
Interestingly recent reports have documented the development of bilateral adrenal necrosis in a number of dogs on trilostane. The likelihood of long-term trilostane treatment leading to increased risk of adrenal necrosis as a result of ACTH hypersecretion and/or direct effects of trilostane or its metabolites is an ongoing area of research.