Determining Type: Adrenal or Pituitary Cushing’s

Once Cushing’s disease has been diagnosed, the next step is identifying the type of Cushing’s. Approximately 85 percent of dogs with Cushing’s have the pituitary-dependent form of the disease, caused by a pituitary tumor. The other 15 percent have the adrenal-dependent form, caused by an adrenal gland tumor. This article provides an overview of how adrenal-dependent and pituitary-dependent Cushing’s disease are distinguished.

Why Classification Matters

The type of Cushing’s disease that’s present can affect a dog’s prognosis. Adrenal tumors have a 50 percent chance of being malignant, so it’s important to know whether this is something that you are dealing with. Veterinarians will want to look for evidence of malignancy, including size of the tumor and whether it has spread to other organs. With a pituitary tumor, there’s less risk of malignancy but a possibility that it will grow and put pressure on the brain. Your veterinarian may want to visualize the pituitary tumor with MRI to determine its size.

Low-Dose Dexamethasone Suppression Test

The LDDST is the most common test for diagnosing Cushing’s disease. As explained below, this test can also identify the type of Cushing’s disease in some cases.

• For this test, dogs are given an injection of a synthetic cortisol called dexamethasone, and three blood samples are collected. The first blood sample is taken prior to the dexamethasone injection and measures baseline cortisol. The second and third samples are taken 4 and 8 hours following the injection.

• If cortisol at both 4 and 8 hours is more than 50% of the baseline, it points strongly to Cushing's but does not indicate whether it is pituitary or adrenal. More tests will be needed to determine the type of Cushing’s.

• If cortisol is (1) below 1.5 ug/dL (or other cutoff established by the laboratory) at 4 hours or (2) less than 50% of the baseline cortisol level at 4 hours or (3) less than 50% of the baseline at 8 hours, it confirms pituitary Cushing’s.

For more insight into LDDST results, see this chart by IDEXX Laboratories. Please note, the numbers used by other laboratories may differ from the ones used by IDEXX.

Imaging

An abdominal ultrasound can provide strong clues about what type of Cushing’s disease is present. In dogs with pituitary-dependent Cushing’s disease, imaging will show two adrenal glands that are the same size and shape and most likely enlarged. Dogs with adrenal-dependent Cushing’s usually have one adrenal gland that is enlarged and potentially misshapen due to a tumor, while the other gland is smaller than normal. Research has shown that ultrasound can correctly identify an adrenal tumor in 86 percent of cases.

High-Dose Dexamethasone Suppression Test

After diagnosing a pet with Cushing’s disease, some veterinarians use the high-dose dexamethasone test to identify the type. It’s similar to the low-dose dexamethasone test but a higher dose of dexamethasone is used. This test is able to confirm pituitary-dependent Cushing’s disease about 70 to 80 percent of the time but cannot confirm adrenal-dependent Cushing’s disease.

Endogenous ACTH

Endogenous ACTH is considered the most accurate way to determine which form of Cushing’s disease a dog has. To conduct this test, veterinarians measure the amount of ACTH in a dog’s bloodstream. High or normal levels of endogenous ACTH typically indicate pituitary-dependent disease, whereas low levels suggest an adrenal tumor.

References

Cushing’s Disease: Classifying the Type, by Wendy Brooks, DVM

Canine Endogenous ACTH, by Gribbles Veterinary

Testing for Cushing’s: Which Diagnostic Approach is Best? By Natalie Marks, DVM