Canine Cushing's Case Files: The ins and outs of detection and treatment-Case file: Boca (Sponsored by Dechra Veterinary Products)

Case file: BOCA, an 8-year-old spayed female Shih Tzu weighing 14 lb (6.4 kg)

Patient history and initial diagnostic workup

Boca was presented to Parkview Veterinary Hospital for evaluation of polyuria, polydipsia, skin lesions, and signs of gastrointestinal discomfort. Boca had a previous history of intermittent gastrointestinal signs including stool that would vary from soft to liquid, inappropriate fecal elimination in the house, and vomiting. These signs had previously improved after her diet was changed to a food containing hydrolyzed protein.

Cynthia Nichols, DVM

Physical examination revealed pain upon abdominal palpation, borborygmi, and calcinosis cutis on the dorsal head and neck.

A serum chemistry profile showed elevated alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) activities. Boca's urine specific gravity was 1.014.

An abdominal ultrasonographic examination revealed a biliary mucocele and hepatomegaly. Bocca was subsequently referred to a veterinary surgeon, and her gallbladder was removed.

Adrenal function test results

An ACTH stimulation test performed two weeks after the gallbladder surgery showed a baseline cortisol concentration of 8.1 µg/dl (reference range = 1.0 to 5.0 µg/dl) and a one-hour post-ACTH cortisol concentration of 44.5 µg/dl (reference range = 8.0 to 17.0 µg/dl). These results were consistent with a diagnosis of hyperadrenocorticism.

Boca, after treatment with VETORYL® Capsules (trilostane) and awaiting re-examination.

I discussed two medical treatment options with the owners—mitotane and VETORYL® Capsules (trilostane). I advised the owners that mitotane was not approved for use in dogs and that I had experience with using mitotane to treat canine hyperadrenocorticism but not with VETORYL Capsules. The owners elected to treat Boca with mitotane in an extra-label fashion.

Initial treatment

After 11 days of once daily treatment with an induction dose of mitotane, Boca's baseline cortisol concentration was 1.0 µg/dl and her one-hour post-ACTH cortisol concentration was 1.1 µg/dl. Based on these results, the induction dose of mitotane was discontinued and a twice-weekly maintenance dose of mitotane was started. A low dose of prednisone was also given on the mitotane treatment days.

After one month on the maintenance dose of mitotane with prednisone, Boca's owners reported that she had diarrhea and lethargy on the days she received mitotane. Boca's baseline cortisol concentration was 2.8 µg/dl and her one-hour post-ACTH cortisol concentration was 5.2 µg/dl. Her ALP, ALT, and GGT activities were still elevated. Boca's diarrhea was managed with supportive care and the prednisone and mitotane were continued at the same dosages.

After one year of treatment with mitotane and prednisone, Boca presented for evaluation of vomiting and diarrhea with tenesmus. Her ALP, ALT, and GGT activities were still elevated. An ACTH stimulation test showed a baseline cortisol concentration of 6.8 µg/dl and a one-hour post-ACTH cortisol concentration of 24.5 µg/dl.

Because Boca would again need to receive mitotane at an induction dose and she had not tolerated mitotane well to date, I recommended discontinuing treatment with mitotane and prednisone and starting treatment with VETORYL® Capsules (trilostane) one month later.

Treatment with VETORYL Capsules

The owners took time to consider their options, and Boca did not receive mitotane or prednisone for more than three months. The owners reported that Boca's water consumption seemed normal, but that her clinical signs of gastrointestinal discomfort recurred, and her calcinosis cutis began to recur as well. The return of her clinical signs and the previously elevated post-ACTH cortisol concentration provided evidence that Boca still had enough functioning adrenal tissue to warrant the use of VETORYL Capsules.

Boca was treated with VETORYL Capsules at 10 mg once daily in the morning with a meal. This commercially available capsule size provided the dose closest to the low end of the labeled dosage range of 1 to 3 mg/lb (2.2 to 6.7 mg/kg). After nine days of VETORYL Capsules treatment, an ACTH stimulation test revealed a baseline cortisol concentration of 9.1 µg/dl and a one-hour post-ACTH cortisol concentration of 14.2 µg/dl. The owners reported that Boca was doing well and experienced no diarrhea or lethargy while receiving VETORYL Capsules.

Her calcinosis cutis was resolving steadily. Boca was continued on the same dose of VETORYL Capsules; the dose was not increased because she was doing well clinically and because of her history of sensitivity to mitotane. Boca's owners were advised to schedule a 30-day posttreatment recheck examination, and Boca's reexamination is pending.

Dr. Nichols' perspective

Boca may have been exhibiting some atypical gastrointestinal signs of hyperadrenocorticism,1-3 along with the more typical clinical signs such as polyuria, polydipsia, and calcinosis cutis. She also had a biliary mucocele, which may be more likely to occur in dogs with hyperadrenocorticism.4

Because Boca would have required reinduction with mitotane and had not tolerated mitotane treatment well, I tried VETORYL Capsules for the first time. It can be intimidating in a complex case such as Boca's to try a new drug and treatment protocol for the first time. I have been pleased with the simplicity of the VETORYL Capsules protocol to treat canine hyperadrenocorticism.

Dr. Nichols is a veterinary practitioner at Parkview Veterinary Hospital in Monterey, Calif.

REFERENCES

1. Hess, RS, Kass PH, Shofer FS, et al. Evaluation of risk factors for fatal acute pancreatitis in dogs. J Am Vet Med Assoc 1999;214(1):46-51.

2. Cook AK, Breitschwerdt EB, Levine JF, et al. Risk factors associated with acute pancreatitis in dogs: 101 cases (1985-1990). J Am Vet Med Assoc 1993;203(5):673-679.

3. Nnichols R. Concurrent illness and complications associated with canine hyperadrenocorticism. Semin Vet Med Surg (Small Anim) 1994;9(3):132-136.

4. Mesich ML, Mayhew PD, Paek M. Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study. J Small Anim Pract 2009;50(12):630-635.

This case was solicited from the prescribing veterinarian and may represent an atypical case study. Similar results may not be obtained in every case.

Hyperadrenocorticism affects many adult dogs. Whether the disease is pituitarydependent (80% to 85% of spontaneous cases) or adrenal-dependent (15% to 20% of cases), the clinical and laboratory abnormalities associated with it result from chronic hypercortisolemia. Clinical signs of hyperadrenocorticism at the time of diagnosis can vary widely, and they develop so gradually that owners often mistake the signs for "normal" aging. Being aware of the more subtle signs of canine hyperadrenocorticism can be key to early diagnosis and initiation of therapy.

Common Clinical Signs of Canine Hyperadrenocorticism

Whenever possible, pituitary-dependent hyperadrenocorticism and adrenal tumors should be differentiated to help guide therapy and patient monitoring. Early diagnosis and management of canine hyperadrenocorticism may not only improve the patient's clinical signs but may also keep the more severe consequences of Cushing's syndrome from developing.

Learn more with these online resources

Go to the Dechra Veterinary Products CE Learning Center at www.dechrace.com and choose one of the online CE modules to learn the latest on managing feline hyperthyroidism and canine hyperadrenocorticism. Plus earn free CE!

• Diagnosing and treating canine hyperadrenocorticism

Presented by Audrey K. Cook, BVM&S, MRCVS, DACVIM, DECVIM, and David s. Bruyette, DVM, DACVIM

• Cushing's disease: Inside and out

Rhonda Schulman DVM, DACVIM, and John Angus, DVM, DACVD

• Diagnosing and treating feline hyperthyroidism

Presented by Andrew J. Rosenfeld, DVM, DABVP

Then get your whole team on the same page, by visiting the Team Meeting in A Box section at www.dechrace.com

• Stop getting burned by ear infections

How you handle otitis externa and ear infections can make or break client bonds—and dogs' well-being. Use this Team meeting in a Box to create a team approach to help pet owners and heal patients.

• Coping with Cushing's syndrome

Pets with Cushing's syndrome suffer from a chronic illness that will be managed throughout the pet's life, not cured. This Team Meeting in A Box will help you deliver a successful team-wide approach.

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