I have not yet found anything from Dr. P about twice day dosing being the better alternative for adrenal tumors though we know that it may be hard to control their cortisol so that could lead to twice day dosing. Zoe has always struggled with her evening dose.

Pros and cons of Lysodren vs Vetoryl
So which drug to use—mitotane or trilostane? If the dog has PDH, she should respond clinically to either drug (1,4-6), but if an expanding pituitary tumor is present, that might lead to neurological signs within a few months (3,7). If the dog has an adrenal tumor, the standard doses of mitotane would be unlikely to help, but this failure to control the cortisol levels would help "suggest" that an adrenal tumor is the underlying cause (1,8,9).
Use of standard doses of trilostane, on the other hand, is more effective in lowering cortisol values in dogs with adrenal tumors so this may be the way to go if the client refuses any additional workup (6,10). However, if adrenal carcinoma is present, this drug would do nothing to stop tumor invasion or metastasis. And again, if the dog has non-suppressible PDH with a pituitary macrotumor, this might lead to neurological signs within a few months.
I
have a patient with an adrenal tumor. If I give VetorylR prior to surgery, will the mass
get smaller?
No. VetorylR has not cytotoxic effects on adrenal tumors. It will not shrink the mass or prevent metastatic spread. However, VetorylR does effectively control the clinical signs of HAC in these patients, and is licensed for use in dogs with adrenal tumors. Surgery is the optimal approach in these cases, but Vetoryl should be considered if the mass is inoperable or if other factors make surgery a poor choice