A veterinarian’s diagnosis of hyperadrenocorticism is done by a combination of physical examination, general laboratory tests, and specific screening tests for high cortisol levels. Several diseases including diabetes, kidney disease, liver disease, hypothyroidism, and hyperthyroidism exhibit signs also seen in hyperadrenocorticism so veterinarians may want to rule out many of these other possibilities before performing specific tests for hyperadrenocorticism. A complete blood count, urinalysis, chemistry profile, and abdominal x-ray or ultrasound will provide the veterinarian with clinical data necessary to aid in the diagnosis. Veterinarians may also request a thyroid profile, since many of the symptoms associated with hyperadrenocorticism are also seen in dogs with hypothyroidism including hair loss, skin problems, lethargy, and weight gain.

Once the general diagnostic testing is performed and a presumptive diagnosis of hyperadrenocorticism is made, the veterinarian will perform specific tests designed to diagnosis hyperadrenocorticism and provide a differential diagnosis of PDH or ADH.

The tests utilized to diagnose hyperadrenocorticism are designed to measure increased levels of cortisol. Cortisol secretion fluctuates throughout the day and although dogs with hyperadrenocorticism have an increased mean cortisol concentration throughout the day a single baseline cortisol test can be normal, therefore use of a single baseline cortisol is not recommended as a screening test. The following tests are used to screen for and differentiate the type of hyperadrenocorticism.

Adrenocorticotropic Hormone (ACTH) Stimulation Test
This test measures the dog’s response to an injection of ACTH. A blood sample is taken before ACTH is administered and another sample is taken generally 1-2 hours after injection providing the laboratory with pre and post blood samples to analyze cortisol levels. Dogs with hyperadrenocorticism will have an increased cortisol response to ACTH stimulation resulting in an abnormally high level of cortisol in the post stimulation blood sample. The ACTH stimulation test cannot differentiate between the pituitary and adrenal forms of the disease but is the only test that can detect iatrogenic hyperadrenocorticism. Iatrogenic hyperadrenocorticism is characterized by a normal or low baseline cortisol level and little or no cortisol response to ACTH stimulation.

Low-Dose Dexamethasone Suppression Test
This test involves the measurement of cortisol levels before the administration of dexamethasone and at 4 and 8-hours post injection. Normally dexamethasone causes the pituitary to stop secretion of ACTH, which will result in a corresponding decrease in cortisol levels. Pituitary and adrenal hyperadrenocorticism does not respond to the suppression effect of dexamethasone and cortisol levels taken 8 hours after the administration of dexamethasone usually remain elevated. A small percentage, approximately 5%, of dogs with PDH will suppress cortisol production, which can result in a missed diagnosis of hyperadrenocorticism. Since both PDH and ADH usually do not respond to the Low-Dose Dexamethasone Suppression Test it is not generally used to differentiate between to the forms of hyperadrenocorticism but only to confirm a diagnosis of hyperadrenocorticism. Sometimes analysis of the 4 and 8-hour post injection samples with respect to the baseline level can result in a differential diagnosis of PDH.

Urine Cortisol-Creatinine Ratio
Since urine cortisol levels are elevated in hyperadrenocorticism, a high ratio of urine cortisol level in relation to the creatinine level is expected. A normal result for this test may be used to rule out hyperadrenocorticism, but elevated ratios are seen in many nonadrenal diseases so this test does not confirm a diagnosis of hyperadrenocorticism.

High-Dose Dexamethasone Suppression Test
This test is generally performed to try and differentiate between the PDH and ADH forms of the disease. Since ADH produces cortisol independent of ACTH secretion, the administration of either a low or high dose of dexamethasone fails to suppress the cortisol level. When a high dose of dexamethasone is administered a majority of the dogs with PDH will exhibit a decrease in cortisol levels due to the suppression of ACTH production.

Plasma ACTH Measurements
Measurement of plasma ACTH concentrations can also be used to differentiate between PDH and ADH. A single baseline plasma ACTH is not useful as a screening test because ACTH secretion fluctuates, frequently dogs with PDH will exhibit normal levels of ACTH on a single test analysis. Measurement of plasma ACTH concentrations can be used to diagnose ADH, since the high cortisol levels produced by ADH suppress ACTH secretion from the pituitary this results in low to undetectable levels of ACTH.