When it comes to Cushing's syndrome, an accurate diagnosis starts with proper patient selection. Let's discuss when clinical signs should raise suspicion, narrowing the patient list, screening tests (and how to interpret their results), and client communication during the decision-making process.

When to Suspect Cushing's Syndrome

The clinical hallmarks of Cushing's syndrome in dogs—polyuria, polydipsia, polyphagia, panting, hepatomegaly or potbelly, muscle wasting, thin skin, recurrent infections, pendulous abdomen, and changes in the hair coat (e.g., alopecia and thinning)—are well recognized. In a study of 115 dogs diagnosed with Cushing's syndrome, the rates of polyphagia, polydipsia, polyuria, panting, and thin skin were 86%, 82.6%, 80%, 74.8%, and 79.1%, respectively.

While these signs alone are not pathognomonic, specific red-flag patterns should raise suspicion:

• Concurrent multiple clinical signs. A dog showing only mild increased thirst is not a strong candidate for testing; however, a dog with polyphagia, polyuria, panting, weight changes, and coat thinning warrants investigation.
• Progressive onset in middle-aged or older dogs. Most cases occur in dogs approximately 8–12+ years old; a sudden change over months rather than years is more concerning.
• Signs that do not respond to routine treatments for standard differentials. For example, if a dog is treated for recurrent urinary or skin infections but fails to improve.
• Laboratory abnormalities on routine screening tests. For example, a patient presenting with elevated alkaline phosphatase (ALP), increased cholesterol/triglycerides, or stress leukogram, combined with common clinical signs.

Rule Out Other Differentials First

Cushing's syndrome patients have several differentials: diabetes mellitus, chronic kidney disease, hepatic disease, hyperlipidemia, pancreatitis, hypothyroidism, hypercalcemia, iatrogenic glucocorticoid use, and even neoplasia.

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But we can also see patients with comorbidities. The 2023 AAHA guidelines emphasize that "practitioners should only test patients when clinical suspicion is high (i.e., presence of two or more clinical or biochemical abnormalities)" and manage any comorbidities before testing. Additionally, concurrent illness or stress can cause false-positive results on adrenal function tests. Completion of a basic workup (CBC, chemistry, urinalysis, thyroid screening, and ruling out or managing differentials) should occur before adrenal testing.

Screening Tests

When it comes to Cushing's syndrome, a strategic testing approach leverages multiple diagnostic tools, each offering distinct clinical value. Screening tests, such as the low-dose dexamethasone suppression test (LDDST), the ACTH stimulation test, and baseline lab findings, work together to build a comprehensive diagnostic picture, with each serving a specific role in patient evaluation.

Urine Cortisol: Creatinine Ratio (UCCR)

This is a simple, low-cost, noninvasive screening tool. Its high sensitivity of 75-100% reduces the likelihood of false negatives.¹ However, this test has lower specificity, resulting in more false positives. Because of this low specificity, clinicians must confirm any positive result with a more specific adrenal function test. UCCR is ideal for ruling out disease in patients with a low suspicion.

Low-Dose Dexamethasone Suppression Test (LDDST)

The 2023 AAHA guidelines indicate that the LDDST is the preferred screening and diagnostic test for spontaneous Cushing's (non-iatrogenic) cases. Measure a baseline cortisol level, administer dexamethasone at 0.01 mg/kg IV, and collect samples at 4 and 8 hours.

If cortisol levels at 8 hours remain above a specific cutoff (e.g., >1.4 µg/dL, depending on the laboratory reference), the lack of suppression raises suspicion of Cushing's syndrome. Partial suppression or escape patterns may indicate pituitary-dependent disease. Although LDDST sensitivity is high (85–100%), the moderate specificity (44–73%) means more false positives.

ACTH Stimulation Test

The ACTH Stimulation Test assesses adrenal responsiveness, measuring cortisol levels before and after administering exogenous ACTH (often synthetic). In a dog with spontaneous Cushing's, cortisol levels rise significantly. The ACTH stimulation test is more specific (fewer false positives) but less sensitive than the LDDST in cases of non-iatrogenic disease. While a positive ACTH test is a compelling piece of evidence, a negative result does not reliably rule out the disease.

The ACTH Stimulation test is the test of choice in suspected iatrogenic disease (i.e., prolonged glucocorticoid administration) or for monitoring response to therapy (e.g., trilostane).

Beyond the previous minimum database recommendations, additional tests to consider include:

• Endogenous ACTH measurement (to help differentiate PDH vs. adrenal tumor)
• Abdominal ultrasound or advanced imaging if localization is necessary or to help rule out adrenal tumors. Recent research demonstrates the usefulness of correlating adrenal size variation and suppression patterns (e.g., partial suppression often seen in bilateral adrenal hyperplasia).

Communicating with Clients

Cushing's syndrome testing is not straightforward; cost, patient stress, and the potential for ambiguous or false-positive results all necessitate clear communication with pet owners to build trust and prevent future conflicts.

Some best practices veterinarians should follow when communicating with clients include:

• Explain the rationale. Guide the pet owner through your reasoning for testing.
• Discuss the diagnostic process. Explain that Cushing's diagnosis often requires multiple data points working together—screening tests, baseline labs, and clinical signs all contribute to the overall picture. False positives and false negatives can occur, especially if the dog has a concurrent illness or is under stress.
• Set expectations from the beginning. Inform clients that in borderline cases, repeat testing or additional diagnostics (i.e., imaging) may be necessary, and at times, the diagnosis may remain uncertain.
• Discuss the cost versus benefit. Choosing to test only "high-risk" patients reduces unnecessary expenses. Explain how testing dogs with only mild or non-specific signs often gives ambiguous results that might do more harm than good.
• Plan a monitoring strategy. If you're not testing immediately, suggest a monitoring schedule that includes rechecking clinical signs and baseline labs in a few months.

Diagnosing Cushing's Syndrome Begins With Patient Selection

Strategic patient selection is the foundation of successful Cushing's diagnosis. The ideal candidate presents with multiple concurrent clinical signs—polyuria/polydipsia, polyphagia, panting, and coat changes—in the appropriate age range (typically 8–12+ years), with other differentials ruled out through baseline diagnostics.

This selective approach delivers measurable benefits: more definitive test results, reduced unnecessary costs for clients, and stronger diagnostic confidence that supports clear treatment recommendations. Equally important, it builds trust. When clients understand why you're recommending testing and why you're not testing prematurely, they recognize your clinical judgment and stewardship of their resources.

By applying this framework consistently, veterinarians can improve diagnostic accuracy, enhance practice efficiency, and improve the client experience—transforming a complex diagnostic challenge into an opportunity for clinical leadership.

References:
1. Bennaim, M., Shiel, R. E., & Mooney, C. T. (2019). Diagnosis of spontaneous hyperadrenocorticism in dogs. Part 1: Pathophysiology, aetiology, clinical and clinicopathological features. The Veterinary Journal, 252, 105342.

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