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

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.

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.

COMMON CLINICAL SIGNS OF CANINE HYPERADRENOCORTICISM

CASE FILE: DALI

10-year-old, spayed female dachshund weighing 9 lb (4.1 kg)

Presenting complaint and history

Dali was referred to Texas A&M's Veterinary Teaching Hospital for evaluation of a mammary mass that had progressively enlarged over a three-month period. Several years before referral, Dali had two malignant mammary masses removed. Dali was receiving levothyroxine, and recent post-pill thyroxine concentrations showed effective control of her hypothyroidism.

Referral evaluation

Dali had a 2- × 3-cm nodular mass (and three smaller nodules) associated with her third right mammary gland. Dali displayed a plantigrade stance of the forelimbs, and her abdomen was pendulous, with thin skin (Figure 1).

FIGURE 1. Dali exhibited thin ventral abdominal skin with poor elasticity.

Laboratory test results

A serum chemistry profile revealed increased alkaline phosphatase, alanine aminotransferase, and gamma glutamyl transferase activities. Dali's serum cholesterol concentration was also increased. A complete blood count showed a stress leukogram with thrombocytosis. Her urine specific gravity was 1.008, and a urine bacterial culture was negative. Although the owner had not reported that Dali exhibited abnormal thirst or excessive urination, the low urine specific gravity indicated polyuria and polydipsia.

Cytologic examination and imaging

The results of a fine-needle aspirate and cytologic examination of the mammary mass indicated carcinoma. Thoracic radiographs were unremarkable; however, abdominal ultrasonography revealed diffuse hyperechoic hepatomegaly, and both adrenal glands were substantially enlarged (Figure 2).

FIGURE 2. An ultrasonographic image of Dali's left adrenal gland reveals adrenomegaly (Image courtesy of Texas A&M Radiology Service).

Differential diagnoses

Dali's tentative diagnoses were mammary carcinoma and hyperadrenocorticism. Although the ultrasonographic findings strongly suggested hyperadrenocorticism, adrenomegaly does not provide a definitive diagnosis. A low-dose dexamethasone suppression (LDDS) test was done to evaluate the pituitary-adrenal axis.

LDDS test results

Dali's LDDS test results indicated hyperadrenocorticism. Although the 4-hour post-dexamethasone cortisol concentration (2.95 µg/dl) was lower than the baseline (4.73 µg/dl) and 8-hour post-dexa-methasone (5.08 µg/dl) cortisol concentrations, it was greater than 1.4 µg/dl (reference range) and did not suppress to more than 50% of the baseline concentration. Therefore, the LDDS test results did not confirm pituitary-dependent hyperadrenocorticism. However, the ultrasonographic findings excluded an adrenal tumor.

Treatment

Prompt removal of Dali's mammary carcinoma was recommended because of its size and metastatic potential. Compromised healing due to hyperadrenocorticism and increased risk of acute perioperative complications such as pulmonary thromboembolism and infection were of concern, but the decision was made to treat the hyperadrenocorticism postoperatively. Dali's potential to develop thromboembolic problems was adequately managed medically, and a mastectomy was performed.

VETORYL® (trilostane) Capsules

The day after surgery, Dali was comfortable and eating well. Treatment for hyperadrenocorticism with VETORYL® (trilostane) Capsules was started, at a dose of 2.4 mg/kg, given orally once daily with food. Dali was discharged later that day and was to continue to receive levothyroxine; antibiotic treatment to prevent postoperative infection was also prescribed.

Dali's owners were told to monitor Dali closely and if problems were observed, to discontinue VETORYL Capsules and have Dali re-evaluated immediately.

Follow-up evaluations and Dali's response

At Dali's recheck visit two weeks later, the incision site appeared to be healing well and the antibiotic therapy was complete. The owner reported that Dali was eating well and urinating less frequently. The results of a serum chemistry profile were similar to the results of a previous one, and Dali's serum electrolyte concentrations were normal. An adrenocorticotropic hormone (ACTH) stimulation test was performed four hours after VETORYL® (trilostane) Capsules administration to assess Dali's adrenal function. The baseline cortisol concentration was 5.3 µg/dl, and the post-ACTH cortisol concentration was 13.8 µg/dl (target post-ACTH cortisol concentration <9.1 µg/dl). Dali's VETORYL Capsules dose was increased to 5 mg/kg once daily.

Four weeks postoperatively

Dali was presented for a recheck examination and suture removal (postponed to allow more time for healing) two weeks later. Dali was doing well at home and was drinking less than before VETORYL Capsules treatment. The skin on her ventrum was still thin, but hair growth was apparent around the surgical site. Her serum electrolyte concentrations were normal. An ACTH stimulation test showed a baseline cortisol concentration of 4.5 µg/dl and a post-ACTH cortisol concentration of 7.7 µg/dl. VETORYL Capsules was continued at the same dose. The owner was advised to present Dali for a recheck examination in four weeks.

Ten weeks postoperatively

Dali was presented six weeks later and the owner reported that Dali was active and energetic. The hair around Dali's surgical site had regrown, and the thickness and elasticity of her ventral abdominal skin had improved. The owner declined laboratory tests other than an ACTH stimulation test. The results were optimal, with a baseline cortisol concentration of 3.3 µg/dl and a post-ACTH covrtisol concentration of 4.4 µg/dl. VETORYL Capsules was continued at 5 mg/kg once daily.

Dali's long-term response

Eighteen months postoperatively, Dali exhibits no evidence of recurrence or metastasis of the mammary carcinoma and her hypothyroidism continues to be managed medically. Her hyperadrenocorticism is effectively controlled with VETORYL Capsules (Figure 3), adjusted from 2.4 mg/kg to 5 mg/kg once daily, depending on her clinical signs and routine laboratory and adrenal function test results.

FIGURE 3. Dali, 18 months after a mastectomy and treatment for hyperadrenocorticism with VETORYL® (trilostane) Capsules. Dali's hair coat and abdominal silhouette are not suggestive of hyperadrenocorticism. She still has a slightly plantigrade stance in the forelimbs.

Dr. Cook's perspective

Dali's case highlights the need to carefully weigh the risks of surgery in a dog with untreated hyperadrenocorticism, such as poor healing, infection, and thromboembolic problems. Also keep in mind that bilateral adrenomegaly is not diagnostic for hyperadrenocorticism and the diagnosis must be confirmed by adrenal function testing.

Concurrent diseases may affect the results of some of these tests. The LDDS test is more sensitive than the ACTH stimulation test, but it is less specific and more likely to be affected by concurrent disease, including neoplasia. Adrenal function test results must always be evaluated carefully in dogs with concurrent diseases, and a high index of suspicion for hyperadrenocorticism should be present before performing either test. Because Dali's small mammary tumors were unlikely to cause systemic illness, we were comfortable diagnosing hyperadrenocorticism based on her clinical examination and routine laboratory and LDDS test results.

As in Dali's case, when treating hyperadrenocorticism with VETORYL Capsules, decisions to adjust the dose should take into account the clinical status of the patient, the cortisol concentrations, and the owner's satisfaction.

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

Audrey K. Cook, BVM&S, MRCVS, DACVIM, DECVIM

For 10 years, Dr. Cook owned a specialty referral practice in Virginia. in 2007, she joined the faculty of Texas A&M University, where she is an associate professor in Small Animal Internal Medicine.

Dr. Audrey K. Cook

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.

Visit www.dechra-us.com to sign up for the Dechra eNewsletter or to see the Latest Events list.