Cushing's disease and other adrenal gland disorders

Cushing's disease and other adrenal gland disorders

A Q&A with veterinary endocrinologist Edward C. Feldman
Jun 01, 2010

Dr. Edward C. Feldman
DVM: In your position at the University of California-Davis School of Veterinary Medicine, you have the opportunity to diagnose and treat a large number of adrenal gland disorders in dogs. Is there any new information that may influence our clinical approach to hyperadrenocorticism?

Feldman: Most studies agree that the ACTH stimulation test is neither sensitive (about 40 percent of dogs with Cushing's have an abnormal result) nor specific (an abnormal result does not consistently indicate that Cushing's is present). No dog should be treated unless it has obvious and worrisome clinical signs seen by the owner.

DVM: That being said, besides a basic database, which diagnostic test do you prefer to perform first if you suspect Cushing's?

Feldman: The most sensitive and specific tests in the diagnosis of Cushing's in dogs are the history (most important) and physical examination (next most important). The urine cortisol-creatinine ratio is quite sensitive but not specific. The low-dose dexamethasone suppression (LDDS) test is sensitive and relatively specific if the test is performed on dogs with appropriate history and physical examination results. I do not recommend an ACTH stimulation test unless iatrogenic disease is suspected.

DVM: How does the presentation of patients with iatrogenic hyperadrenocorticism differ from other cases of Cushing's disease, and how do you approach diagnosis and treatment in these patients?

Feldman: Iatrogenic and naturally occurring Cushing's are clinically indistinguishable. While the ACTH stimulation test is an inferior screening test for naturally occurring Cushing's, it is the gold standard for the diagnosis of iatrogenic cases. If a dog looks, smells and feels like it has Cushing's and if an iatrogenic source is suspected, an ACTH stimulation test should be performed. Treatment could not be easier: Stop the steroids.

DVM: Could you outline how your treatment recommendations change when you suspect an adrenal tumor as the cause of hyperadrenocorticism?

Feldman: Dogs with a cortisol-secreting adrenal tumor should be treated for eight to 16 weeks with trilostane. The initial dose should be about 0.5 mg/kg twice a day. Then, assuming that good control has been achieved for about eight weeks, surgical removal of the adrenal tumor should be performed. Remember that a large percentage of adrenal masses extend into the vena cava or other major blood vessels, so it is important that the surgeon be experienced in removing such masses.

DVM: So has trilostane become your first choice in the treatment of hyperadrenocorticism, or do you continue to use mitotane (o,p'-DDD)? Is there a particular protocol you use if you switch between the two medications to avoid possible complications, in light of a couple of reported cases of acute adrenocortical necrosis following a switch?

Feldman: Trilostane is my first choice in dogs with an adrenal tumor. My first choice for dogs with pituitary-dependent hyperadrenocorticism is mitotane. However, trilostane at an initial dose of 0.5 mg/kg given twice daily is an excellent second choice. No veterinarian should consider the use of trilostane before thoroughly reading the insert provided with the drug — not the insert for pet owners, the insert for veterinarians. Any dog switched from one to the other should receive no medication for at least six weeks.

Regarding adrenal necrosis: Both mitotane and trilostane have been linked with adrenal necrosis. Mitotane, as a cytotoxic drug, certainly acts by killing cells. Trilostane, however, is the only drug that has been associated with necrosis, adrenal rupture, acute bleeding, related illness and/or death. Therefore, switching from one drug to the other may not be the cause of necrosis or rupture, since this adverse reaction has been demonstrated to occur in dogs that have only received trilostane. Mitotane has not been associated with adrenal rupture.

DVM: Given that there are different causes, diagnostics and treatment options for dogs with Cushing's, are there any areas of client communication that you feel many practitioners could handle better?