A general practitioner’s guide to Cushing syndrome

Sigma s / stock.adobe.com

Hyperadrenocorticism, or Cushing syndrome, is a common differential diagnosis in older dogs presenting with PU/PD or elevated Alkaline Phosphatase (ALP). But "[Cushing] syndrome is one of the most over-diagnosed diseases in veterinary medicine,” according to Lawren Durocher-Babek, DVM, MS, DACVIM, CHPV of Zodiac Pet and Exotic Hospital in Fortress Hill, Hong Kong. During a session at the 2023 American Veterinary Medical Association Convention, in Denver, Colorado, Durocher-Babek discussed the need for careful patient and test selection when hyperadrenocorticism is suspected and shared pearls for medical management of the disease.¹

Which patients should be tested for Cushing syndrome?

Appropriate patient selection is critical when testing for hyperadrenocorticism. Durocher-Babek’s minimum database for a dog presenting with polyuria and polydipsia or as a Cushing suspect includes a thorough physical examination with rectal palpation, a complete blood count, chemistry panel with electrolytes, urinalysis, and blood pressure.

An abdominal ultrasound may or may not be included in the initial series of tests. Durocher-Babek tends to do abdominal ultrasound sooner rather than later. “Most of the patients we see with [hyperadrenocorticism] are older and we are worried about other things like cancer,” she stated. An abdominal ultrasound will help to rule out conditions like cancer and can help to differentiate between adrenal-dependent and pituitary-dependent Cushing syndrome.

Ultimately, "there is no lab abnormality or clinical sign that is pathognomonic for hyperadrenocorticism," said Durocher-Babek. The list of clinical signs and laboratory abnormalities that may be seen in patients with hyperadrenocorticism is lengthy. Durocher-Babek suggests creating a checklist of these abnormalities and considering how many are present in an individual patient. There is a higher likelihood a patient has Cushing and stronger support for testing as the number of abnormalities present increases.

Durocher-Babek recommends testing patients with large numbers of clinical and laboratory abnormalities consistent with hyperadrenocorticism, patients diagnosed with a pituitary or adrenal mass, and patients with persistent hypertension. For diabetic patients showing signs of insulin resistance, Cushing testing should only be tested if they have been under treatment for at least a month and have yet to be controlled.

“I have more guidelines for who not to test than who to test,” Durocher-Babek stated. Sick and hospitalized patients should never be tested for hyperadrenocorticism. She reminded practitioners that “patients with Cushing disease feel great. They are running—or waddling—in to see us. Testing for hyperadrenocorticism is never an emergency.” Testing can wait until patients are eating well and concurrent diseases have been managed for some time. Additionally, newly diagnosed diabetics, patients with inappetence or anorexia, and patients without consistent clinical signs are poor candidates for testing.

What test should be used?

The screening test of choice for Cushing’s syndrome is the low dose dexamethasone suppression (LDDS) test, which assesses if cortisol production can be turned off in the body. With a sensitivity of 85-100%, there are fewer false negatives than are seen with some of the other available tests.

In some cases, such as for diabetic patients, those on phenobarbital, or in cases of suspected iatrogenic Cushing syndrome, an ACTH stimulation test is the preferred test. This test assesses the adrenocorticoid reserves.

A Urine cortisol creatinine ratio (UCCR) can be used as a screening test but will not provide a definitive diagnosis. The test has a sensitivity of 75-100%, so a negative result can be used to rule out hyperadrenocorticism. The urine sample should be collected at home at least 2 days after a veterinary visit or other stressful event. This test may be a good choice for clients who are concerned about Cushing syndrome in a patient with few or no clinical signs.

For patients that are highly suspicious for hyperadrenocorticism but do not have a consistent test, Durocher-Babek recommends doing the opposite test (eg, if LDDS was performed, run an ACTH stimulation test) or waiting 3 months and retesting. An adrenal panel from the University of Tennessee is available as well. Treatment should not be started until a positive test result is obtained.

How should patients be treated?

Durocher-Babek reminds veterinarians that even after a diagnosis of hyperadrenocorticism, treatment is optional. Patients that feel good, have clinical signs (especially if they are affecting patient or owner quality of life), or have comorbidities that would benefit from controlling the Cushing syndrome are good candidates for treatment as long as their owners can keep up with treatment and monitoring, which can be costly. Patients with a poor appetite, vomiting, diarrhea, or other clinical illness should not be treated.

“The treatment of choice for pituitary-dependent hyperadrenocorticism and adrenal-dependent hyperadrenocorticism that can’t have surgery is trilostane,” said Durocher-Babek. It is the only FDA-approved treatment for hyperadrenocorticism in dogs, is available in multiple sizes, is reversible, and usually well tolerated with transient side effects. “Irreversible adrenal gland damage can occur but is much less common than with mitotane,” Durocher-Babek stated. “What I see is the biggest problem [with trilostane] is people start too high and start once a day,” she continued, recommending a starting dose of 0.5 mg/kg twice daily and increasing as needed.

Durocher-Babek cautions veterinarians “not to expect miracles overnight” once treatment is started. Generally, clinical signs of PU/PD will begin to decrease within 4 weeks of treatment. Dermatologic changes can take 6 months, and achieving good control of the disease may take 10 months. Patience is key when treating patients with hyperadrenocorticism and owner expectations should be managed early.

Monitoring of hyperadrenocorticism can be complex with several different protocols available, including an ACTH stimulation test 3 to 4 hours post-pill or a pre-pill cortisol level. Ultimately, “the owner’s perception of clinical signs is the most important monitoring tool,” said Durocher-Babek. A history is essential for all patients coming in for examinations while on trilostane. Any testing performed is to ensure that cortisol levels are not going too low and can help to know how much room to adjust the dosage there is.

Take-home points

When testing for Cushing syndrome, patient selection is critical for accurate results. Although the screening test of choice is the low dose dexamethasone suppression test, some patients, such as diabetics, should have an ACTH stimulation test performed instead. If the results are consistent with Cushing syndrome, treatment with trilostane can be started if consistent clinical signs are present. Although there are several strategies for monitoring, the owner’s perception of clinical signs should be a key component.

Reference

Durocher-Babek L. The Cushing’s conundrum: When should we test, how should we test, and what do we do with the results? Presented at 2023 AVMA Convention: Denver, Colorado. July 15, 2023.

Dr Boatright, a 2013 graduate of the University of Pennsylvania, is a practicing veterinarian and freelance speaker and author in western Pennsylvania. She is passionate about mentorship, education, and addressing common sources of stress for veterinary teams and recent graduates. Outside of clinical practice, Dr. Boatright is actively involved in organized veterinary medicine at the local, state, and national levels.