Adrenal cortisol testing. Although multiple clinical diagnostic tests are available, there isn't always a single correct diagnostic pathway that will
point to Cushing's disease. Some clinical tests that can help in diagnosis include:
—Urine cortisol/creatinine ratio. In animals with Cushing's disease, excess cortisol is excreted by the kidneys, increasing the amount of cortisol in comparison
to the normal concentrations of creatinine in the urine.
—ACTH stimulation. In a dog fasted 12 hours, serum is obtained to determine a pre-stimulation cortisol concentration. Then ACTH (pituitary
hormone) is given, either intramuscularly or intravenously, depending on the form of ACTH. One or two hours later (again,
depending on the ACTH form), a post-stimulation cortisol concentration is obtained. Hyperadrenocortical patients show a significant
increase (far above normal response to ACTH) of cortisol concentrations after stimulation due to hypertrophic adrenal glands.
Although this test can confirm a patient suffers from hyperadrenocorticism, it does not distinguish the pituitary-dependent
from the adrenal-dependent (adrenal tumor) form of Cushing's disease.
—Low-dose dexamethasone suppression. In a fasted animal, serum is obtained for measurement of cortisol at the time of injection of dexamethasone sodium phosphate
and then again four and eight hours later. An intravenously administered dexamethasone dose of 0.015 mg/kg is used. A patient
with a normal pituitary-adrenal axis will respond by suppressing the endogenous cortisol to concentrations below the reference
range (different with each laboratory) at both four and eight hours post-injection. A patient with hyperadrenocorticism won't
respond to the dexamethasone; subsequently the endogenous cortisol concentration will remain above the reference range at
the eight-hour measurement. The four-hour measurement can be useful because some patients with pituitary-dependent hyperadrenocorticism
will have suppressed concentrations of cortisol at four hours, but the concentration will "escape" or rise above the normal
range at the eight-hour measurement. In this instance, the test will confirm both the disease (Cushing's) and the form (pituitary-dependent).
Note, some pituitary-dependent cases of Cushing's disease will not show a suppressed cortisol concentration at four hours post-dexamethasone. It's expected that a patient with a functional
adrenal tumor will have endogenous cortisol concentrations that remain increased, or not suppressed, at both four and eight
hours post-dexamethasone. This test is considered by many to be more sensitive at confirming a patient with Cushing's, but
not as specific as an ACTH stimulation test. Other systemic illnesses, such as diabetes mellitus or renal or liver disorders,
may result in false-positive low-dose dexamethasone suppression.
—High-dose dexamethasone suppression. This test can be performed to distinguish the pituitary-dependent from the adrenal-dependent form of hyperadrenocorticism,
but only after confirming this disease exists by either the ACTH stimulation test or the low-dose dexamethasone suppression
test. In this test, a high-dose (1 mg/kg) of dexamethasone is injected intravenously. With pituitary-dependent Cushing's disease,
most pituitary tumors will decrease the ACTH concentration in the presence of higher dexamethasone concentrations. The decreased
ACTH decreases endogenous cortisol concentrations. In adrenal-dependent Cushing's disease, three out of four adrenal tumors
won't suppress cortisol concentrations after the injection of the high-dose dexamethasone. Note, both false positive and false
negative results are possible when using high-dose dexamethasone to differentiate pituitary from adrenal forms of hyperadrenocorticism.
—Abdominal ultrasonography. Once hyperadrenocorticism is suspected through routine clinical diagnostic tests or a Cushing's screening test (i.e., urine
cortisol/creatinine ratio), abdominal ultrasonography can detect adrenal gland changes. Specifically, ultrasonography can
help detect three disorders: 1) pituitary-dependent disease, or enlargement (one to two times normal size) of both adrenal
glands due to increased ACTH production from the pituitary gland, resulting in bilateral hyperplasia; 2) adrenal tumors, that
is, moderate enlargement of one adrenal gland and atrophy of the second gland secondary to negative feedback of increasing
cortisol concentrations and decreasing ACTH concentrations; and 3) pheochromocytoma (epinephrine-producing tumor of the adrenal
medulla), that is, a moderate-to-severe enlargement of one adrenal gland, while the other gland usually is normal in size.
Identification and diagnosis of endocrinopathies requires close attention to medical history, physical examination findings,
identification of secondary infections and a thorough clinical diagnostic database. The medical team must be able to isolate
abnormal findings that may suggest the presence of a subtle underlying disease process. These changes help the veterinarian
determine if more specific endocrine or allergy testing should be done.
Dr. Lewis sees dermatology patients in California, Arizona, Nebraska, New Mexico, Nevada and Utah. In 1991, he established
Dermatology for Animals, PC. Dr. Rosenfeld is the founder and president of VTEC. He has practiced small-animal critical care
and emergency medicine for 20 years and is currently working as a general practitioner and running a mobile ultrasound practice
in Cape Cod, Mass.
1. Scott DW, Miller Jr. WH, Griffin CE. Muller and Kirk's small animal dermatology. Baltimore, Md: Elsevier, 2000.
2. Feldman EC, Nelson RW. Canine and feline endocrinology and reproduction. 3rd ed. Baltimore, Md: Elsevier, 2003.
3. Rosenfeld A. The veterinary medical team handbook. Ames, Iowa: Wiley Blackwell, 2007.