Hyperadrenocorticism (HAC) results from excess cortisol secretion by the adrenal cortex. Approximately 85% of dogs with this disease secrete excess adrenocorticotropic hormone (ACTH) from the pituitary gland, resulting in bilateral adrenocortical hyperplasia (termed pituitary-dependent HAC or PDH). The remaining dogs with HAC have an adrenocortical tumor (AT), adenoma or carcinoma, which secretes cortisol independent from the hypothalamic-pituitary-adrenal axis. About half of the ATs are calcified and can be seen radiographically. Abdominal ultrasound may also aid in visualizing these tumors.

The most common clinical signs are polyuria/polydipsia, polyphagia, panting, weakness, and endocrine alopecia. Common blood chemistry abnormalities include elevations in serum alkaline phosphatase, SGPT (ALT), cholesterol, and blood glucose. A "stress leukogram" may also be seen.

When HAC is suspected, begin with a screening test to confirm the diagnosis (ACTH Stimulation Test or Low-Dose Dexamethasone Suppression Test) and follow with a test that differentiates PDH from an AT (Endogenous ACTH Level or High-Dose Dexamethasone Suppression Test). A single basal cortisol concentration can be difficult to interpret because cortisol is secreted episodically, resulting in normal dogs and those with HAC having overlapping values.

The principal behind this test is that dogs with PDH or AT have abnormally large adrenal cortisol reserves. Therefore, they can potentially hyperrespond to a maximal ACTH stimulation. The ACTH Stimulation Test is reliable for diagnosing HAC in 80-85% of affected dogs. The test is simple to perform, it distinguishes spontaneous from iatrogenic HAC (little to no increase in post ACTH cortisol), and provides baseline cortisol information, which may be helpful in monitoring op-DDD (Lysodren) therapy.

Protocol:

1. Collect baseline blood sample for cortisol determination (serum or plasma).
   
2. Give synthetic ACTH (Cortrosyn) – 5 mcg/kg to maximum of 0.25 mg (250 mcg)/dog IV or IM. Unused portion can be stored refrigerated for one year without loss of potency.
   
3. Collect blood one hour later for cortisol determination.

In normal dogs, pituitary ACTH stimulates adrenocortical synthesis and secretion of glucocorticoids. In turn, the rising plasma concentrations of glucocorticoids suppress continued secretion of ACTH via negative feedback. The result is the maintenance of plasma cortisol concentrations. Exogenous dexamethasone given to normal dogs results in suppression of endogenous ACTH secretion. Dogs with HAC, on the other hand, are abnormally resistant to suppression by exogenous dexamethasone.

This test is somewhat more reliable than the ACTH Stimulation Test in confirming HAC. Results will be diagnostic in 90-95% of dogs with HAC. Furthermore, the LDDST can differentiate between PDH and AT if a pattern of suppression and escape is seen. The disadvantages of the test are that it takes 8 hours to perform, it cannot differentiate between spontaneous HAC and iatrogenic HAC, and the test does not provide pre-treatment information which may aid in monitoring the effects of Lysodren.

Protocol:

1. Collect baseline blood sample for cortisol determination (serum or plasma).
   
2. Give Dexamethasone sodium phosphate (0.01 mg/kg IV) or dexamethasone in polyethylene glycol [Azium] (0.015 mg/kg IV).
   
3. Collect blood for cortisol determination 4 and 8 hours after dexamethasone administration.

Results:
Cortisol concentration greater than 1.4 ug/dl at 8 hours, in a dog with compatible clinical signs, is consistent with a diagnosis of HAC. Cortisol concentrations between 1.0 and 1.4 ug/dl are nondiagnostic.

If the LDDST result is normal, yet clinical signs/history are consistent with HAC and no other disease process can be determined, retest in 1-2 months.

CAVEAT: Nonadrenal illness can cause a false positive result in all of the above tests. Test results should be interpreted in conjunction with clinical signs, history and baseline bloodwork.