Several tests are available on the market, each with its own strengths, limitations, and ideal applications; careful consideration is always necessary.

Below, we'll guide veterinarians through selecting the appropriate diagnostic test for Cushing's. The most suitable test depends on the patient's presentation, clinical history, and available resources, highlighting the importance of correlating test results with clinical signs and coexisting diseases.

Correlating Test Choice with Clinical Presentation

Cushing's presents with a variety of clinical signs, including polyuria/polydipsia (PU/PD), polyphagia, hair loss, muscle wasting, and a pot-bellied appearance. However, these signs are not unique to Cushing's and can mimic other diseases like diabetes mellitus, liver disease, and chronic kidney disease.

To avoid misdiagnosis and unnecessary testing, veterinarians should consider clinical signs, medical history, and concurrent diseases along with test results.

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Opting for one test with specific criteria instead of casting a wide net also helps the practice-client relationship. Running multiple tests on a patient with vague clinical signs can cause unnecessary stress for both the patient and the pet parent. Veterinary teams must have a strong clinical suspicion of the patient, along with supporting laboratory findings, to warrant testing for Cushing's. In other words, if a patient presents with vague clinical signs or clinical signs that are unsupportive of this disease (ie, anorexia), initial testing for Cushing's would be discouraged, as this can be costly, time-consuming, and likely unproductive in these cases.

Testing for Cushing's is divided into two categories: screening tests, which include the low-dose dexamethasone test and the ACTH stimulation test, and, if a screening test is positive, differentiating tests, which include the high-dose dexamethasone suppression test, endogenous ACTH concentrations, and advanced imaging. In all cases, a screening test must be performed before moving on to a differentiating test protocol.

Below, we'll discuss the benefits, drawbacks, and use cases for each of these diagnostic methods.

The Role of the Low-Dose Dexamethasone Suppression Test

Veterinarians primarily use the low-dose dexamethasone suppression test (LDDST) as a screening tool and one of the most common ways to diagnose Cushing's syndrome in dogs. This test assesses the adrenal glands' ability to suppress cortisol production in response to dexamethasone, a synthetic glucocorticoid. In healthy dogs, the administration of dexamethasone typically suppresses cortisol secretion. However, in dogs with Cushing's syndrome, cortisol levels remain abnormally high.

This test is typically preferred for most cases, as it has a sensitivity of 85-95%, making it a primary screening strategy for Cushing's. This test has a few limitations (i.e., low specificity, which can produce false positives in animals with other diseases, including diabetes and hypothyroidism). Still, the results of the LDDST are always evaluated in conjunction with clinical signs and other diagnostic results.

Differentiating Pituitary vs. Adrenal Disease

While the LDDST is a valid initial screening test for Cushing's, it can also be used, based on the pattern of results, to help differentiate between pituitary-dependent hyperplasia (PDH) and adrenal tumors. The LDDST pattern in PDH cases exhibits up to 50% suppression of the baseline or reference range at the 4-hour mark, but a high cortisol level (due to escape) at the 8-hour mark. This early suppression is diagnostic for PDH because adrenal tumors, in contrast, never suppress at either the 4-hour or 8-hour blood draw.

Differentiation with High-Dose Dexamethasone Suppression

While an LDDST can be both a screening and differentiation test, the high-dose dexamethasone suppression test (HDDST) has historically been used for differentiation. The HDDST is similar to the LDDST but uses a higher dose of dexamethasone. However, with the advent of advanced imaging and endogenous ACTH testing, the HDDST has mostly fallen out of favor.

Differentiation with Advanced Imaging

Conversely, advanced imaging, such as abdominal ultrasonography, has become increasingly important for diagnosing and distinguishing between the two forms of Cushing's. In general practice, abdominal ultrasonography can not only help screen and identify adrenal tumors or masses but also ensure that no other abdominal disease is present. For pet parents and clinicians alike, this testing often proves highly useful, especially when differentiation may alter the treatment course or serve as prognostic indicators before medical therapy.

Real-Time Cortisol Diagnostics

Advances in diagnostic technology have made real-time testing more accessible and efficient for diagnosing Cushing's. Point-of-care cortisol assays enable faster and more accurate assessments of cortisol levels.

This accessible testing is not only helpful when Cushing's is suspected, but can also be used to monitor the effectiveness of ongoing treatment. Veterinary clinics with in-house labs can perform real-time cortisol measurements while the patient is present, providing immediate results. This enables veterinarians to evaluate and modify treatment promptly.

The ACTH Stimulation Test for Monitoring and Suspected Iatrogenic Cushing's Syndrome

While veterinarians primarily use the LDDST for initial diagnosis (and some may use HDDST as a follow-up differentiating test), they find the ACTH stimulation test particularly valuable. They use it for monitoring treatment response in patients receiving trilostane or mitotane, and they also employ it to diagnose Iatrogenic Cushing's syndrome. Exogenous corticosteroid administration causes Iatrogenic Cushing's. In cases where time with the patient is limited, the ACTH stimulation test may be preferable, as it takes two hours rather than eight, offering real-time results.

Tailoring the Diagnostic Approach for Cushing's Syndrome

As veterinary hospitals shape their diagnostic approach to Cushing's, there are two critical points to remember. There are two steps to the diagnostic process: screening and differentiation, followed by associated testing in each category, which must follow a correct order. The second critical piece to remember is to ensure that a strong clinical suspicion is present, along with an appropriate clinical history, to correlate with testing results. The pairing of a patient with several clinical signs and appropriate screening tests, such as the LDDST, lends itself to the most accurate diagnosis and corresponding treatment plan.