New possible Cushings treatments work at root cause

Dr. Dave BruyetteEvery year an estimated 90,000 to 100,000 new cases of Cushing's disease are diagnosed in geriatric dogs, making it the most common endocrine disease in older canine patients. Many of these cases are treated with drugs such as mitotane or trilostane, which reduce cortisol and help with clinical signs, but neither works at the level of the pituitary.

David S. Bruyette, DVM, DACVIM, medical director VCA West Los Angeles Animal Hospital, says dopaminergic drugs may provide another treatment option that does just that. “Historically we've used medications that attack the adrenal; we don't address the primary problem, which is the pituitary tumor,” Bruyette told dvm360 recently.

Up to 40 percent of these tumors overexpress the D2 dopamine receptor in dogs, he says, and drugs that bind with high affinity to the dopaminergtic receptor actually shrink the tumors. They also decrease adrenocorticotropic hormone (ACTH) production, which then lowers cortisol-so these drugs treat clinical signs of Cushing's as well.

“There is a drug commercially available called cabergoline that was used in a large number of dogs in a study out of Argentina, and the drugs seem quite effective in normalizing clinical signs as well as shrinking the tumors-at least in dogs with relatively small tumors,” Bruyette says.

Further studies have examined the receptor abnormalities expressed by the pituitary tumors that cause Cushing's, he continues. Researchers are actively looking at epithelial growth factor receptor (EGFR) antagonists as well as somatostatin receptor antagonists.

Bruyette says use of a human drug called pasireotide, an SST2 receptor antagonist, looks promising for treatment of dogs as well. “A recent study in dogs with fairly small tumors showed that not only did they get reductions in ACTH and reductions in urine cortisol-creatinine ratios but also modest shrinkage in some of these tumors,” he says.

Larger studies will examine whether use of drugs such as pasireotide are effective for treating dogs with larger tumors without radiation and surgery.

“Hopefully, some of these newer treatments that have recently come available for humans will become available for use in the dog,” Bruyette says.