Hyperadrenocorticism (HAC; ie, hypercortisolemia, Cushing's syndrome) is one of the most common endocrinopathies in dogs. Dogs with HAC have excessive glucocorticoid concentrations, typically resulting from a pituitary or adrenal tumor. Treatment goals include optimizing quality of life, eliminating clinical signs (eg, polydipsia, polyuria, polyphagia, alopecia, muscle weakness), and reducing long-term complications and mortality.
Management of HAC is continually evolving. Understanding how therapies differ in mechanism, onset, and safety is essential for tailoring treatment to each patient. Detailed information on agent selection and use is available through Plumbs.com.
Treatment Options for Hyperadrenocorticism
Trilostane is FDA-approved to treat pituitary-dependent hyperadrenocorticism (PDH) and adrenal-dependent hyperadrenocorticism (ADH) in dogs. This drug reversibly inhibits production of progesterone, thereby decreasing glucocorticoid, mineralocorticoid, and sex steroid production. The FDA-approved starting dose is often considered higher than necessary to control clinical signs and associated with a high rate of adverse effects, and lower initial doses are recommended.1-3 Trilostane should be administered with food. This drug is very effective, and clinical signs (eg, polydipsia, polyphagia, lethargy) gradually improve over the first few weeks of treatment. The dose should be adjusted based on clinical signs and ACTH stimulation testing. Although this drug is generally well tolerated, hypoadrenocorticism can develop at any dose and at any time during therapy.4-7 Survival times in dogs treated with trilostane are greater than in untreated dogs and are equivalent to or possibly slightly longer than in dogs treated with mitotane.8-13 Trilostane is generally considered the treatment of choice for dogs with HAC.
Mitotane causes necrosis of the zona fasciculata and zona reticularis in the adrenal cortex, resulting in decreased glucocorticoid and sex steroid production. Mitotane usually has little effect on the zona glomerulosa, and aldosterone synthesis is largely unaffected. Mitotane is particularly effective in cases of PDH but also is effective in cases of ADH.14-16 In dogs with PDH, this drug should be initially administered twice daily until clinical signs are controlled but not longer than 8 to 10 days, at which time ACTH stimulation testing can be performed; dogs can be transitioned to maintenance treatment (ie, once or twice weekly) when pre- and post-ACTH cortisol concentrations are acceptable and clinical signs are controlled. A longer induction phase is needed for dogs with adrenal tumors. Hypoadrenocorticism is a frequent clinical sequela and prednisone/prednisolone may be needed.
Due to the risk for hypoadrenocorticism associated with trilostane and mitotane, pet owners should be instructed to contact the clinic immediately if the dog experiences vomiting, diarrhea, lethargy, poor/reduced appetite, weakness, collapse, or any other unusual developments. Prescribing a small supply of prednisone/prednisolone for the owner to have in case of emergency can be considered.
Ketoconazole, an antifungal agent, also inhibits steroid synthesis. Although this drug has demonstrated some efficacy for treatment of HAC, unacceptably high rates of adverse effects (eg, anorexia, vomiting, diarrhea, increased liver enzymes) limit usefulness.17,18
Selegiline (ie, L-deprenyl) is FDA-approved to control clinical signs in dogs with PDH; however, efficacy is poor and adverse effects are common.19,20