Challenges in diagnosing hyperadrenocorticism in dogs (Proceedings)

Hyperadrenocorticism can be pituitary-dependent (PDH), secondary to cortisol-secreting adrenocortical neoplasia, or iatrogenic. Spontaneous hyperadrenocorticism is primarily a disease of middle-aged to older dogs. All breeds can be affected but poodles, dachshunds, Boston terriers and boxers appear to be at greater risk of developing PDH. Adrenal tumors are more common in larger dogs (>20 kg). No sex predilection is seen in dogs with PDH. In contrast, two-thirds of dogs with adrenal tumors are female.

Evaluation of a dog with suspected hyperadrenocorticism involves the confirmation of hyperadrenocorticism followed by differentiation between PDH and adrenal tumors. Tests for diagnosing hyperadrenocorticism include the ACTH stimulation test, the low dose dexamethasone suppression test and the urine cortisol:creatinine ratio. Imaging studies and plasma ACTH levels are typically used to differentiate PDH from adrenal tumors.

The ACTH stimulation test is performed by obtaining a serum sample for cortisol determination before and 1 hour after IV injection of 5 ug/kg of the synthetic ACTH (Cortrosyn). Once reconstituted, the solution appears to be stable for at least 4 weeks if refrigerated. Alternatively, the remaining solution can be aliquoted and frozen. If necessary ACTH gel can be used. Acthar Gel (80 U/ml, Rhone Poulenc) is available but is very expensive. ACTH gel (usually 40 or 80 U/ml) is available from various compounding pharmacies. The dose is 2.2 U/kg IM; samples should be taken at 0, 1 and 2 hours. The bioavailability and reproducibility of these various formulations has not been stringently evaluated. Therefore, it may be prudent to assess the activity of each new vial by performing an ACTH stimulation test on a normal dog.

The low dose dexamethasone suppression test is performed by obtaining serum samples for cortisol determination before and 4 and 8 hours after IV or IM administration of 0.01 or 0.015 mg/kg dexamethasone. In normal dogs, serum cortisol concentrations are suppressed below 1 ug/dL (30 nmol/L) by 4 hours after administration of dexamethasone and remain suppressed at 8 hours. In contrast, cortisol concentrations in most dogs with hyperadrenocorticism remain above 1 ug/dL (30 nmol/L) during the 8-hour test period. Some laboratories use a 1.5 ug/dL cutoff for the diagnosis of hyperadrenocorticism and consider the 1.0 to 1.5 ug/dL range a "grey zone". About 25% of dogs show a pattern of "escape" from suppression (<1 ug/dL at 4 hours and >1.5 ug/dL at 8 hours), a pattern diagnostic for PDH. About 5% of dogs with hyperadrenocorticism will have a normal test result. The test should be repeated in 3 to 6 months if clinical signs of hyperadrenocorticism persist.

The urine cortisol:creatinine ratio is a convenient screening test for hyperadrenocorticism. The sample should be collected at home by the owner rather than in the hospital. A normal value makes a diagnosis of hyperadrenocorticism very unlikely. A positive (elevated) result must be confirmed with an ACTH stimulation test or a low-dose dexamethasone suppression test.

Endogenous plasma ACTH determination reliably distinguishes PDH from adrenal tumors in most cases. Contact the appropriate laboratory for collection and shipping instructions. Dogs with pituitary-dependent hyperadrenocorticism have a normal to high ACTH levels (>40 pg/ml), whereas dogs with adrenal tumors have low or undetectable plasma levels of ACTH (<20 pg/ml).

Ultrasonography is more sensitive than radiography for imaging the adrenal glands and is a recommended part of the workup of all dogs with hyperadrenocorticism, but is a very dependent technique on the quality and resolution of the equipment and the skill and experience of the ultrasonographer. Bilateral adrenomegaly is found in most dogs with pituitary-dependent hyperadrenocorticism, though some are found not to have enlarged adrenal glands. An adrenal mass is usually readily identified in dogs with adrenal neoplasia. The contralateral adrenal is atrophied and difficult to find. Bilateral adrenal tumors are very rare. In dogs with adrenal neoplasia, evaluate the liver for metastasis and the caudal vena cava for tumor thrombus. CT and MR imaging are accurate means of assessing the pituitary and adrenal glands in dogs with hyperadrenocorticism, but are less available and require anesthesia.