Top 5 Roadblocks When Navigating Cushing’s Syndrome

ArticleJanuary 20235 min readSponsored
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Most veterinary practitioners diagnose and manage many patients with Cushing’s syndrome (ie, hyperadrenocorticism) over their career, with the disease having an estimated overall prevalence of 0.2% in client-owned dogs.1 Although some cases of Cushing’s syndrome may be straightforward, the condition can also pose a number of challenges throughout the diagnosis and management process.

Explore how to navigate these 5 common hurdles that can be encountered on the way to a stable Cushing's patient.

1. Recognizing Clinical Signs

Clients may dismiss signs of Cushing’s syndrome as signs of aging, neglecting to mention these changes to their veterinarian. Therefore, it is important to ask direct questions to help clients recognize the signs of Cushing’s syndrome, including decreased activity, polyuria/polydipsia, polyphagia, panting, pendulous abdomen, endocrine alopecia, and muscle weakness.2

2. Knowing When to Test

It is important to keep in mind that not every alkaline phosphatase (ALP) elevation indicates Cushing’s syndrome. If clinical signs and physical examination findings are consistent with Cushing’s syndrome, only then should endocrine testing begin.2 Even a single sign of Cushing’s syndrome is an indication for investigation due to the risks for thromboembolic disease, diabetes mellitus, and other conditions that may accompany untreated Cushing’s syndrome.3

3. Selecting the Right Diagnostic Test

Three screening tests are available for canine patients, each with unique advantages and disadvantages:

  • Low-dose dexamethasone suppression (LDDS) test: This is the screening test of choice.2,4 It has a sensitivity of 85% to 100%2 and can differentiate pituitary-dependent hyperadrenocorticism (PDH) from adrenal-dependent hyperadrenocorticism (ADH) in ≈50% of cases.4

  • Adrenocorticotropic hormone (ACTH) stimulation test: The sensitivity for the diagnosis of Cushing’s syndrome is reportedly as low as 57%.2 However, an ACTH stimulation test is the best screening test for suspected iatrogenic Cushing’s syndrome.2,4

  • Urine cortisol:creatinine ratio (UCCR): This can be a beneficial screening tool but cannot provide a diagnosis. This test is sensitive (75%-100%) but nonspecific (20%-25%) and is heavily influenced by patient stress levels.2 If a client is uncertain about whether to pursue testing for Cushing’s syndrome, a UCCR may be beneficial as a preliminary step to help rule out Cushing's syndrome.

Following the diagnosis of Cushing’s syndrome, additional differentiating tests may be required. The distinction between PDH and ADH is important, even if surgery is not an option should an adrenal tumor be found. Dogs with adrenal tumors often require higher doses of trilostane3 and may also need to undergo additional testing to acquire prognostic information. Differentiating tests include endogenous ACTH levels, LDDS test, adrenal ultrasonography, and/or pituitary imaging (CT or MRI).5

4. Treating Cushing’s Syndrome

In cases of PDH, which constitutes 80% to 85% of cases,5 lifelong treatment and monitoring is necessary. The only FDA-approved treatment for Cushing’s syndrome in dogs is Vetoryl® Capsules (trilostane). Dosing is initiated at 2.2-6.7 mg/kg daily,5 starting at the low end of the dosing range and increasing based on monitoring. Compounded trilostane should be avoided, as studies have shown it to have unreliable safety and efficacy.3

Other options for the treatment of pituitary-dependent Cushing’s syndrome exist but have disadvantages. Selegiline is FDA-approved for the treatment of uncomplicated PDH, but studies demonstrate low efficacy.6 Mitotane has historically been used to treat Cushing’s syndrome but is not FDA-approved for this indication, and its use can be complex and accompanied by many potential side effects.7

5. Monitoring Patients & Educating Pet Owners

Once treatment has been initiated, it is important to monitor the patient closely, especially at home by the pet owner. Any signs of lethargy, weakness, anorexia, and/or vomiting should be taken seriously and may indicate oversuppression of cortisol production and the development of hypoadrenocorticism.8

Patients receiving Vetoryl should be monitored with an ACTH stimulation test 10 to 14 days after starting medication.5 Based on test results and the patient’s clinical signs, dosing may be adjusted and another ACTH stimulation test performed 10 to 14 days later. Once the patient’s optimal dosage has been identified, ACTH stimulation tests should ideally be performed every 90 days.

For a variety of reasons, including financial constraints, alternative monitoring protocols may be unavoidable. The following tips may be useful in these scenarios:

  • A cosyntropin dose as low as 1 µg/kg can be used in ACTH stimulation tests to monitor a patient on Vetoryl,3 which can reduce testing costs.

  • Performing only a post-ACTH cortisol level may also be a way to decrease client costs while still providing valuable information.

  • A pre-pill cortisol level can be used to monitor clinically well patients. If the pre-pill cortisol level is ≥1.5 µg/dL, continuing on the same dose is likely safe. However, if the patient’s pre-pill cortisol level is below 1.5 µg/dL, a full ACTH stimulation test is indicated.

Conclusion

Cushing’s syndrome can pose a number of challenges for the practitioner. Clinical signs may be difficult to recognize, and obtaining an accurate diagnosis can be logistically challenging. Once a pet is diagnosed with Cushing’s syndrome, lifelong therapy and regular monitoring are required.

Being prepared to address roadblocks along the way can increase practitioner efficacy and allow the veterinary team to provide greater benefits for clients and patients.


IMPORTANT SAFETY INFORMATION

As with all drugs, side effects may occur. In field studies and post-approval experience, the most common side effects reported were: anorexia, lethargy/depression, vomiting, diarrhea, elevated liver enzymes, elevated potassium with or without decreased sodium, elevated BUN, decreased Na/K ratio, hypoadrenocorticism, weakness, elevated creatinine, shaking, and renal insufficiency. In some cases, death has been reported as an outcome of these adverse events. VETORYL Capsules are not for use in dogs with primary hepatic or renal disease, or in pregnant dogs. Refer to the prescribing information for complete details.


The Clinician's Brief and Dechra teams would like to thank Cynthia Ward, VMD, PhD, DACVIM (SAIM), for her involvement and expertise in this article.

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