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.

Regardless of the basal cortisol value obtained, diagnosis of HAC depends upon demonstration of a post-ACTH cortisol concentration higher than the normal canine post-ACTH range (normal post range is 6-17 ug/dl). Post-stimulation values between 17-22 ug/dl are considered borderline, and those of > 22 ug/dl are consistent with a diagnosis of HAC.

If HAC is suspected in a dog with normal or only slightly abnormal ACTH Stimulation Test results, the Low-Dose Dexamethasone Suppression Test is then recommended, or the ACTH test is repeated in 1-2 months.

Low-Dose Dexamethasone Suppression Test (LDDST)

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.

1. Collect blood for baseline 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.

Basal and 8 hour post-dexamethasone samples are the most important for interpretation. However, a sample taken at 4 and 6 hours during the test period may be helpful in differentiating PI3H from AT. If cortisol is suppressed to below 1.4 ug/dl at 4 hours after dexamethasone administration, while the 8 hour sample shows escape from suppression (greater than 1.4 ug/dl), a diagnosis of PDH can be made.

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.

The principle of this test is that a high dose of dexamethasone inhibits pituitary ACTH secretion through the glucocorticoid negative feedback effect. The decrease in circulating ACTH results in a decrease in adrenal secretion of cortisol. Functioning ATs secrete high levels of cortisol autonomously which, in turn, suppress ACTH secretion via negative feedback. In these dogs, administration of dexamethasone at any dose cannot suppress ACTH secretion or serum cortisol concentrations any further. In dogs with PDH, on the other hand, the threshold for glucocorticoid negative feedback on ACTH secretion is higher than normal. Thus, high doses of dexamethasone can, but not always, suppress the exaggerated ACTH secretion and thereby decrease serum cortisol concentrations.

1. Collect baseline sample for cortisol determination (serum or plasma).
2. Give Dexamethasone sodium phosphate (2 dosage options are used: either 0.1 mg/kg IV or 1.0 mg/kg IV. Minimal side-effects have occurred with the higher dose).
3. Collect blood sample 8 hours after dexamethasone for determination of plasma cortisol.

Results:

1) Suppression of cortisol concentration to less than 50% of the baseline concentration or less than 1.4 ug/dl 8 hours after administration is consistent with PDH. A CT scan or MRI is required to make the distinction between a microadenoma or macroadenoma.

2) Cortisol values greater than 1.4 ug/dl at 8 hours are indicative of either PDH or AT. Fifteen percent of dogs with PDH fail to suppress at 8 hours. To differentiate between PDH and AT, an endogenous ACTH level, CT scan or MRI is required.

Endogenous Plasma ACTH Levels

This test is used for differentiating between PDH and AT. It is performed after a diagnosis of HAC is made.

Protocol:

1. Antech will furnish EDTA tubes containing aprotinin which stabilizes ACTH. Draw tube until filled, separate plasma into plastic tube and send to lab. DOES NOT have to be frozen.

or

2. Collect sample in "siliconized" EDTA tube on ice, centrifuge immediately, separate into plastic tubes, freeze immediately and ship on dry ice.

Results:

PDH – usually greater than 45 pg/ml. A normal to high plasma ACTH level in dogs with PDH indicates secretion of excessive amounts of ACTH by a pituitary tumor or a defect in the CNS negative feedback mechanism.