When a dog presents with signs of hypoadrenocorticism or hyperadrenocorticism, the first step is to assess the function of the adrenal glands. There are a number of common tests that may be used for this purpose, each with its own unique pros and cons.

Urine cortisol-creatinine ratio (UCCR)

This test looks at the cortisol level in the urine (adjusted for urine output), based on the idea that hypercortisolemia will be reflected as an increased cortisol in the urine. 

A UCCR can be used as a preliminary screening test for Cushing’s disease, in order to determine whether a more definitive workup is indicated. A normal UCCR rules out Cushing’s disease, while an elevated UCCR suggests the need for further testing. 

ACTH stimulation test

This test can be used in the workup of both Cushing’s disease and Addison’s disease. It is the preferred test for the diagnosis of Addison’s disease. It can be used to diagnose Cushing’s disease, although there are other tests that are generally regarded as more sensitive.

ACTH stimulation test protocol: 

• Collect a baseline blood sample.
• Inject 5 ug/kg Cortrosyn^® IV or inject 1 IU/lb ACTH gel (to a maximum of 40 IU) IM. 
• Draw a second blood sample after one hour (if using Cortrosyn^®) or two hours (if using ACTH gel).

Failure to produce adequate cortisol levels in response to ACTH stimulation is diagnostic for Addison’s disease. Continued production of elevated cortisol levels, even after ACTH stimulation, is diagnostic for Cushing’s disease. 

Low-dose dexamethasone suppression (LDDS) test

This test is typically regarded as the preferred test for the diagnosis of Cushing’s disease. It is more sensitive for the diagnosis of Cushing’s disease than the ACTH stimulation test, less expensive than the ACTH stimulation test, and also can differentiate between pituitary-dependent and adrenal-dependent Cushing’s in approximately 30% of dogs.¹ The primary drawback of this test is that it requires 8 hours of hospitalization to perform, which may be an inconvenience for some clients. 

LDDS protocol: 

• Collect an initial blood sample.
• Inject dexamethasone (0.01 mg/kg) IV. 
• Draw a second blood sample 4 hours post-dexamethasone. 
• Draw a third blood sample 8 hours post-dexamethasone. 

Dogs with an elevated cortisol level at 8 hours post-dexamethasone likely have Cushing’s disease (although false positives may rarely occur). If a dog has normal cortisol levels at 8 hours post-dexamethasone, Cushing’s disease is unlikely (although false negatives may also occur). Dogs with unexpected results should receive an ACTH stimulation test for confirmation. 

Once you have diagnosed Cushing’s disease on the basis of an elevated cortisol at 8 hours post-dexamethasone, you can look at localization. If over 50% suppression of baseline cortisol is observed at 4 or 8 hours post-dexamethasone, the dog can be diagnosed with pituitary-dependent Cushing’s and no further testing is needed. If the dog does not suppress to that extent, additional testing is needed to distinguish between pituitary-dependent and adrenal-dependent Cushing’s disease. 

High-dose dexamethasone suppression (HDDS) test

This is a differentiating test, used for dogs that have been diagnosed with Cushing’s disease with an ACTH stim or a LDDS. It is used solely to distinguish between pituitary-dependent and adrenal-dependent Cushing’s disease. 

HDDS protocol: 

• Collect an initial blood sample.
• Inject dexamethasone (0.1 mg/kg) IV. 
• Draw a second blood sample 4 hours post-dexamethasone. 
• Draw a third blood sample 8 hours post-dexamethasone. 

If a dog did not show suppression in the LDDS, but does show suppression on the HDDS, pituitary-dependent Cushing’s disease is likely. However, some dogs may show poor suppression even with pituitary-dependent Cushing’s disease, so adrenal ultrasound is recommended to confirm suspected adrenal tumors. 

Adrenal ultrasound

Ultrasound can be used to distinguish between pituitary-dependent and adrenal-dependent Cushing’s disease in a dog that has been diagnosed with another test. A dog with adrenal-dependent Cushing’s will have unilateral adrenomegaly (due to neoplasia), while a dog with pituitary-dependent Cushing’s will have bilateral adrenomegaly (due to pituitary stimulation). 

Summary: Which Test is Best?

If you suspect Addison’s disease, there’s only one diagnostic test that you should consider: an ACTH stimulation test. If the dog presents in crisis, it’s okay to administer dexamethasone before performing the ACTH stim. (Any other corticosteroid may interfere with the results of your ACTH stim.) 

If you suspect that a dog has Cushing’s disease, you have more options for diagnostics. In general, it’s best to start with a LDDS, because this test is sensitive and may even allow you to distinguish pituitary vs. adrenal-dependent Cushing’s disease. (If your client has financial constraints, however, you might want to begin with a UCCR, to see if it supports the need for further workup. If a client is reluctant to drop their pet off for 8 hours, you could even begin with an ACTH stimulation test.) If you diagnose Cushing’s on the LDDS but are unable to identify its cause, you can then perform a HDDS or adrenal ultrasound for localization.

References

1. Kerl ME. Diagnosing and Treating Cushing’s Disease. DVM360. 2011. Retrieved from: https://www.dvm360.com/view/make-it-happen-personal-and-practice-financial-growth-for-veterinarians